In vitro and in vivo evaluation and a case report of intense nanosecond pulsed electric field as a local therapy for human malignancies.
When delivered to cells, very short duration, high electric field pulses (nanoelectropulses) induce primarily intracellular events. We present evidence that this emerging modality may have a role as a local cancer therapy. Five hematologic and 16 solid tumor cell lines were pulsed in vitro. Hematologic cells proved particularly sensitive to nanoelectropulses, with more than a 60% decrease in viable cells measured by MTT assay 96 hr after pulsing in 4 of 5 cell lines. In solid tumor cell lines, 10 out of 16 cell lines had more than a 10% decrease in viable cells. AsPC-1, a pancreatic cancer cell line, demonstrated the greatest in vitro sensitivity among solid tumor cell lines, with a 64% decrease in viable cells. When nanoelectropulse therapy was applied to AsPC-1 tumors in athymic nude mice, responses were seen in 4 of 6 tumors, including clinical complete responses in 3 of 6 animals. A single human subject applied nanoelectropulse therapy to his own basal cell carcinoma and had a complete pathologic response. In summary, we demonstrate that electric pulses 20 ns or less kill a wide variety of human cancer cells in vitro, induce tumor regression in vivo, and show efficacy in a single human patient. Therefore, nanoelectropulse therapy deserves further study as a potentially effective cancer therapy.
Garon
Edward B
EB
Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. egaron@mednet.ucla.edu
Sawcer
David
D
Vernier
P Thomas
PT
Tang
Tao
T
Sun
Yinghua
Y
Marcu
Laura
L
Gundersen
Martin A
MA
Koeffler
H Phillip
HP
D000818:Animals; D002280:Basal Cell Carcinoma / Q000628:therapy; D045744:Cell Line, Tumor; D004599:Electric Stimulation Therapy / Q000379:methods*; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000628:therapy; D012878:Skin Neoplasms / Q000628:therapy; D014407:Tumor Cells, Cultured