title: Cutaneous papilloma and squamous cell carcinoma therapy utilizing nanosecond pulsed electric fields (nsPEF).
abstract: Nanosecond pulsed electric fields (nsPEF) induce apoptotic pathways in human cancer cells. The potential therapeutic effective of nsPEF has been reported in cell lines and in xenograft animal tumor model. The present study investigated the ability of nsPEF to cause cancer cell death in vivo using carcinogen-induced animal tumor model, and the pulse duration of nsPEF was only 7 and 14 nano second (ns). An nsPEF generator as a prototype medical device was used in our studies, which is capable of delivering 7-30 nanosecond pulses at various programmable amplitudes and frequencies. Seven cutaneous squamous cell carcinoma cell lines and five other types of cancer cell lines were used to detect the effect of nsPEF in vitro. Rate of cell death in these 12 different cancer cell lines was dependent on nsPEF voltage and pulse number. To examine the effect of nsPEF in vivo, carcinogen-induced cutaneous papillomas and squamous cell carcinomas in mice were exposed to nsPEF with three pulse numbers (50, 200, and 400 pulses), two nominal electric fields (40 KV/cm and 31 KV/cm), and two pulse durations (7 ns and 14 ns). Carcinogen-induced cutaneous papillomas and squamous carcinomas were eliminated efficiently using one treatment of nsPEF with 14 ns duration pulses (33/39 = 85%), and all remaining lesions were eliminated after a 2nd treatment (6/39 = 15%). 13.5% of carcinogen-induced tumors (5 of 37) were eliminated using 7 ns duration pulses after one treatment of nsPEF. Associated with tumor lysis, expression of the anti-apoptotic proteins Bcl-xl and Bcl-2 were markedly reduced and apoptosis increased (TUNEL assay) after nsPEF treatment. nsPEF efficiently causes cell death in vitro and removes papillomas and squamous cell carcinoma in vivo from skin of mice. nsPEF has the therapeutic potential to remove human squamous carcinoma.
authors.affiliation: Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of California Los Angeles School of Medicine, Los Angeles, California, United States of America. yin_dong@yahoo.com
authors.forename: Dong
authors.initials: D
authors.lastname: Yin
authors.forename: Wangrong G
authors.initials: WG
authors.lastname: Yang
authors.forename: Jack
authors.initials: J
authors.lastname: Weissberg
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Goff
authors.forename: Weikai
authors.initials: W
authors.lastname: Chen
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kuwayama
authors.forename: Amanda
authors.initials: A
authors.lastname: Leiter
authors.forename: Hongtao
authors.initials: H
authors.lastname: Xing
authors.forename: Antonie
authors.initials: A
authors.lastname: Meixel
authors.forename: Daria
authors.initials: D
authors.lastname: Gaut
authors.forename: Fikret
authors.initials: F
authors.lastname: Kirkbir
authors.forename: David
authors.initials: D
authors.lastname: Sawcer
authors.forename: P Thomas
authors.initials: PT
authors.lastname: Vernier
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Said
authors.forename: Martin A
authors.initials: MA
authors.lastname: Gundersen
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D053672:Electrochemotherapy; D018274:Electroporation; D051379:Mice; D010212:Papilloma / Q000628:therapy*; D012878:Skin Neoplasms / Q000628:therapy*