@article{RN181,
   author = {Ivey, J. W. and Latouche, E. L. and Sano, M. B. and Rossmeisl, J. H. and Davalos, R. V. and Verbridge, S. S.},
   title = {Targeted cellular ablation based on the morphology of malignant cells},
   journal = {Sci Rep},
   volume = {5},
   pages = {17157},
   note = {2045-2322
Ivey, Jill W
Latouche, Eduardo L
Sano, Michael B
Rossmeisl, John H
Davalos, Rafael V
Verbridge, Scott S
R21 CA192042/CA/NCI NIH HHS/United States
R21CA192042/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
England
2015/11/26
Sci Rep. 2015 Nov 24;5:17157. doi: 10.1038/srep17157.},
   abstract = {Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100 μs) is enhanced for larger cells, short pulses (~1 μs) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors.},
   keywords = {Animals
Brain Neoplasms/pathology/therapy/*veterinary
Cell Line, Tumor
Cell Nucleus Size
Cell Shape
Cell Survival
Coculture Techniques
Dog Diseases/pathology/*therapy
Dogs
Electroporation
Finite Element Analysis
Glioblastoma/pathology/therapy/*veterinary
Humans
Hydrogels/chemistry
Single-Cell Analysis},
   ISSN = {2045-2322},
   DOI = {10.1038/srep17157},
   year = {2015},
   type = {Journal Article}
}