{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:52:50Z","timestamp":1790776370375,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,3,27]],"date-time":"2020-03-27T00:00:00Z","timestamp":1585267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Pulse Biosciences Inc."}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Lasers Surg Med"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>Nano\u2010pulse stimulation (NPS) therapy is the application of ultrafast pulses of high amplitude electrical energy to tissues to influence cell function. Unique characteristics of these pulses enable electric field penetration into the interior of cells and organelles to generate transient nanopores in both organelle and plasma membranes. The purpose of this study is to document the temporal and physical changes in intracellular organelles following NPS therapy using electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design\/Materials and Methods<\/jats:title><jats:p>Liver tumors were induced in five buffalo rats by implanting syngeneic McA\u2010RH7777 hepatocellular carcinoma cells into the surgically exposed livers. Tumors were allowed to grow for 1 week and then the surgically exposed livers were treated <jats:italic>in situ<\/jats:italic> with NPS energy delivered at a sufficient level to trigger regulated cell death in the tumor. Samples of NPS\u2010treated and control tissue were removed and fixed for electron microscopy at 1\u2009minute, 5\u2009minutes, 30\u2009minutes, 2\u2009hours and 4\u2009hours after exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Measurements of cellular organelles indicate strong swelling following NPS therapy exposure compared with untreated controls. The mean diameter of the mitochondria increased by 55% within 1\u2009minute and then by 2.5\u2010fold by 2\u2009hours post\u2010NPS therapy. The rough endoplasmic reticulum (RER) cisternae swelled immediately after NPS therapy with reduced swelling by 30\u2009minutes and loss of structural integrity by 2\u2009hours. The Golgi apparatus appears swollen in images collected 1 and 5\u2009minutes after NPS therapy and was no longer detected at 30\u2009minutes and 2\u2009hours post\u2010NPS therapy. By 4\u2009hours after NPS therapy, a nascent Golgi apparatus was detected in many of the images. The plasma membrane lost its well\u2010defined morphology and became less linear, exhibiting discontinuities as early as 1\u2009minute post\u2010NPS energy exposure and the nuclear envelope became subjectively less distinct over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NPS therapy at sufficient energy levels causes the rapid swelling of organelles, disintegration of the RER, breaks in the plasma membrane and blurs the borders of the nuclear envelope. These changes in the mitochondria and RER are indicative of a regulated cell death process. These immediate physical changes to vital cell organelles are likely to trigger subsequent regulated cell death mechanisms observed in other studies of NPS therapy. Lasers Surg.\u00a0Med. \u00a9 2020 The Authors. <jats:italic>Lasers in Surgery and Medicine<\/jats:italic> published by Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/lsm.23239","type":"journal-article","created":{"date-parts":[[2020,3,27]],"date-time":"2020-03-27T12:17:54Z","timestamp":1585311474000},"page":"882-889","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Nano\u2010Pulse Stimulation Induces Changes in the Intracellular Organelles in Rat Liver Tumors Treated In Situ"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-3194","authenticated-orcid":false,"given":"Richard","family":"Nuccitelli","sequence":"first","affiliation":[{"name":"Pulse Biosciences  3957 Point Eden Way Hayward California 94545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"McDaniel","sequence":"additional","affiliation":[{"name":"Pulse Biosciences  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