High-frequency irreversible electroporation(H-FIRE)is a technique that uses pulsed electric felds that have been shown to ablate malignant cells.In order to evaluate the clinical potential of H-FIRE to treat glioblast...High-frequency irreversible electroporation(H-FIRE)is a technique that uses pulsed electric felds that have been shown to ablate malignant cells.In order to evaluate the clinical potential of H-FIRE to treat glioblastoma(GBM),a primary brain tumor,we have studied the efects of high-frequency waveforms on therapy-resistant glioma stem-like cell(GSC)populations.We demonstrate that patient-derived GSCs are more susceptible to H-FIRE damage than primary normal astrocytes.Tis selectivity presents an opportunity for a degree of malignant cell targeting as bulk tumor cells and tumor stem cells are seen to exhibit similar lethal electric feld thresholds,signifcantly lower than that of healthy astrocytes.However,neural stem cell(NSC)populations also exhibit a similar sensitivity to these pulses.Tis observation may suggest that diferent considerations be taken when applying these therapies in younger versus older patients,where the importance of preserving NSC populations may impose diferent restrictions on use.We also demonstrate variability in threshold among the three patient-derived GSC lines studied,suggesting the need for personalized cell-specifc characterization in the development of potential clinical procedures.Future work may provide further useful insights regarding this patient-dependent variability observed that could inform targeted and personalized treatment.展开更多
基金This work was supported by the National Cancer Institute of the National Institutes of Health through awards R21CA192042,R01CA213423,and P01CA207206by a National Science Foundation CAREER Award(CBET-1652112).
文摘High-frequency irreversible electroporation(H-FIRE)is a technique that uses pulsed electric felds that have been shown to ablate malignant cells.In order to evaluate the clinical potential of H-FIRE to treat glioblastoma(GBM),a primary brain tumor,we have studied the efects of high-frequency waveforms on therapy-resistant glioma stem-like cell(GSC)populations.We demonstrate that patient-derived GSCs are more susceptible to H-FIRE damage than primary normal astrocytes.Tis selectivity presents an opportunity for a degree of malignant cell targeting as bulk tumor cells and tumor stem cells are seen to exhibit similar lethal electric feld thresholds,signifcantly lower than that of healthy astrocytes.However,neural stem cell(NSC)populations also exhibit a similar sensitivity to these pulses.Tis observation may suggest that diferent considerations be taken when applying these therapies in younger versus older patients,where the importance of preserving NSC populations may impose diferent restrictions on use.We also demonstrate variability in threshold among the three patient-derived GSC lines studied,suggesting the need for personalized cell-specifc characterization in the development of potential clinical procedures.Future work may provide further useful insights regarding this patient-dependent variability observed that could inform targeted and personalized treatment.
