Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth

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dc.contributor.authorSano, Michael B.en
dc.contributor.authorArena, Christopher B.en
dc.contributor.authorBittleman, Katelyn Roseen
dc.contributor.authorDeWitt, Matthew R.en
dc.contributor.authorCho, Hyung J.en
dc.contributor.authorSzot, Cchristopher S.en
dc.contributor.authorSaur, Dieteren
dc.contributor.authorCissell, James M.en
dc.contributor.authorRobertson, John L.en
dc.contributor.authorLee, Yong Wooen
dc.contributor.authorDavalos, Rafael V.en
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.contributor.departmentVirginia-Maryland College of Veterinary Medicineen
dc.date.accessioned2017-01-27T19:43:12Zen
dc.date.available2017-01-27T19:43:12Zen
dc.date.issued2015-10-13en
dc.description.abstractIrreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions. High-frequency IRE (H-FIRE), a new treatment modality which replaces the monopolar IRE pulses with a burst of bipolar pulses, has the potential to resolve these clinical challenges. We explored the pulse-duration space between 250 ns and 100 μs and determined the lethal electric field intensity for specific H-FIRE protocols using a 3D tumor mimic. Murine tumors were exposed to 120 bursts, each energized for 100 μs, containing individual pulses 1, 2, or 5 μs in duration. Tumor growth was significantly inhibited and all protocols were able to achieve complete regressions. The H-FIRE protocol substantially reduces muscle contractions and the therapy can be delivered without the need for a neuromuscular blockade. This work shows the potential for H-FIRE to be used as a focal therapy and merits its investigation in larger pre-clinical models.en
dc.description.versionPublished versionen
dc.format.extent13 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/srep14999en
dc.identifier.issn2045-2322en
dc.identifier.urihttp://hdl.handle.net/10919/74441en
dc.identifier.volume5en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000362634100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectnonthermal irreversible electroporationen
dc.subjectin-vivoen
dc.subjectradiofrequency ablationen
dc.subjectpancreatic-canceren
dc.subjecttissue ablationen
dc.subjectmouse modelen
dc.subjectsafetyen
dc.subjectelectrochemotherapyen
dc.subjectefficacyen
dc.subjecttherapyen
dc.titleBursts of Bipolar Microsecond Pulses Inhibit Tumor Growthen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineeringen
pubs.organisational-group/Virginia Tech/Engineering/Biomedical Engineering and Mechanicsen
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen

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