Résumé
Incomplete tumor ablation within the peripheral sublethal zone remains a critical limitation of cryoablation for pancreatic ductal adenocarcinoma (PDAC). This study aimed to enhance ablative efficacy by optimizing freezing parameters and integrating combination chemotherapy. A GelMA-based 3D tissue model was initially employed to characterize thermal gradients and define lethal thresholds. Subsequently, a programmable freezer simulated sublethal conditions (-10 to -25 ◦C) to evaluate specific freezing protocols on PANC-1 and BxPC-3 cells. Results demonstrated that an optimized protocol comprising rapid cooling (50 ◦C min-1), extended hold, and dual cycles significantly elevated the effective lethal isotherm. Mechanistic investigation revealed a temperature-dependent shift in cell death modalities: apoptosis predominated at -13 ◦C, whereas necrosis became dominant at ≤-15 ◦C. This transition was underpinned by intensified intracellular reactive oxygen species accumulation and mitochondrial depolarization as freezing temperatures decreased. Furthermore, combining cryoablation with gemcitabine-based regimens markedly suppressed post-cryoablation viability. Notably, cryoablation induced a significant chemo sensitizing effect. In PANC-1 cells, low-dose chemotherapy (1/10th of the high dose) achieved efficacy comparable to high-dose regimens at temperatures ≤-13 ◦C. Conversely, BxPC-3 cells retained dosesensitivity down to -13 ◦C. In conclusion, optimizing cryoablation parameters expands the effective ablative zone and synergizes with low-dose chemotherapy via enhanced oxidative stress and mitochondrial dysfunction, offering a promising strategy for PDAC treatment.
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Détails
- Titre original : Optimized cryoablation and combinatorial chemotherapy overcome sublethal survival in pancreatic cancer cells.
- Identifiant de la fiche : 30035279
- Langues : Anglais
- Sujet : Technologie
- Source : International Journal of Refrigeration - Revue Internationale du Froid - vol. 189
- Date d'édition : 09/2026
- DOI : http://dx.doi.org/https://doi.org/10.1016/j.ijrefrig.2026.107003
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