Date of Award

Summer 2008

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Committee Director

R, James Swanson

Committee Member

Karl H. Schoenbach

Committee Member

Christopher J. Osgood

Committee Member

Stephen J. Beebe

Abstract

High intensity nanosecond pulsed electric fields (nsPEF) were applied to melanoma tumors to observe functional and structural biological changes and to investigate the possible molecular mechanisms responsible. An animal model was set up by injecting B16F10 mouse melanoma cells into SKH-1 mice. A treatment (Tx) of 100 pulses: 300 nanosecond duration; 40 kV/cm field strength; at 0.5 Hz rate were delivered to melanoma tumors in 120 mice. The nsPEF Txcaused tumor self-destruction with sharply decreased cell volumes and shrunken nuclei. The apoptotic biochemical tests confirmed nsPEF Tx induced apoptosis in a time-dependent manner. Examination of gross vessel and micro-vessel density indicated direct vascular damage to pre-existing vessels and antiangiogenic consequence on neovascular development concomitant with tumor self-destruction. A five-month survival study on 36 mice showed nsPEF Tx eliminated tumors with no recurrence to the primary site over the five months. In contradistinction to ionization, thermal or electroporation Tx, nsPEFs produced broad impacts on the melanomas in vivo, ranging from DNA fragmentation, caspase activation, nuclear damage, apoptosis induction, damage to pre-existing infra-tumoral vessels and neovascular inhibition. These tumor responses were expressed by histological and biochemical changes in both short and long term trials. The data indicate nsPEF Tx acts as non-chemical, non-thermal and non-ligand stimulus that can ablate melanomas in vivo.

DOI

10.25777/r67s-m265

ISBN

9780549753155

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