4.5 Article

Quantitative analysis of contribution of mild and moderate hyperthermia to thermal ablation and sensitization of irreversible electroporation of pancreatic cancer cells

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JOURNAL OF THERMAL BIOLOGY
卷 115, 期 -, 页码 -

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtherbio.2023.103619

关键词

Irreversible electroporation; Mild hyperthermia; Thermal ablation; In vitro experiments; Mathematical models; Cell death probability

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IRE is an effective ablation technique for unresectable cancers. This study investigates the impact of mild and moderate hyperthermia on the electroporation effect and establishes a cell viability model. The results indicate that higher temperatures enhance cell ablation and the cell viability model successfully predicts temperature-dependent outcomes.
Introduction: Irreversible electroporation (IRE) is an ablation modality that applies short, high-voltage electric pulses to unresectable cancers. Although considered a non-thermal technique, temperatures do increase during IRE. This temperature rise sensitizes tumor cells for electroporation as well as inducing partial direct thermal ablation. Aim: To evaluate the extent to which mild and moderate hyperthermia enhance electroporation effects, and to establish and validate in a pilot study cell viability models (CVM) as function of both electroporation parameters and temperature in a relevant pancreatic cancer cell line. Methods: Several IRE-protocols were applied at different well-controlled temperature levels (37 degrees C & LE; T & LE; 46 degrees C) to evaluate temperature dependent cell viability at enhanced temperatures in comparison to cell viability at T = 37 degrees C. A realistic sigmoid CVM function was used based on thermal damage probability with Arrhenius Equation and cumulative equivalent minutes at 43 degrees C (CEM43 degrees C) as arguments, and fitted to the experimental data using Non-linear-least-squares-analysis. Results: Mild (40 degrees C) and moderate (46 degrees C) hyperthermic temperatures boosted cell ablation with up to 30% and 95%, respectively, mainly around the IRE threshold Eth,50% electric-field strength that results in 50% cell viability. The CVM was successfully fitted to the experimental data. Conclusion: Both mild-and moderate hyperthermia significantly boost the electroporation effect at electric-field strengths neighboring Eth,50%. Inclusion of temperature in the newly developed CVM correctly predicted both temperature-dependent cell viability and thermal ablation for pancreatic cancer cells exposed to a relevant range of electric-field strengths/pulse parameters and mild moderate hyperthermic temperatures.

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