Non-Ionizing Radiation with Nanosecond Pulsed Electric Fields as a Cancer Treatment: In Vitro Studies

Eastern Virginia Medical School and Frank Reidy Research Center for Bioelectrics, Old Dominion University, USA.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:6509-12. DOI: 10.1109/IEMBS.2009.5333139
Source: PubMed

ABSTRACT Cancer continues to be a major risk to the health and well being among populations around the world. A new method using ion-ionizing radiation with nanosecond pulsed electric fields (nsPEFs) provides a novel means to treat cancer at local sites. NsPEFs promote cell death in several cell types and here we investigated mechanisms for cell death induction. In murine B16f10 melanoma, murine E4 squamous carcinoma, murine Hep1-6 and human HepG2 hepatocellular carcinoma, nsPEFs induced cell death in 90-95% of cells. Cell death coincides with decreases in the mitochondria membrane potential, increases in YO-PRO-1 uptake and active caspases in the presence or absence of cytochrome c release. The results indicate that nsPEFs induced cell death by multiple apoptosis mechanisms that involve mitochondrial responses, but not necessarily through cytochrome c release. Further, these in vitro studies suggest a potential to induce cell death that bypasses cancer mechanisms that evade apoptosis.

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    • "New research has focused on decreasing the treatment time to nanosecond levels in order to decrease the side effects of PEF on a food's main structure. Nano-level application of PEF is being used for cancer and tumor therapy in human cells (Zygulska and Pawlega, 2008; Beebe et al., 2009; Donthula et al., 2009; Mi et al., 2009a, 2009b; Yang et al., 2009). Katsuki and others (2002) applied PEF in ultra short pulses (nanosecond PEF) and set the electric field amplitude to 130 kV/s and pulse width to 45 ns. "
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    ABSTRACT: We have developed a low energy direct current pulsed electric field therapy for tissue ablation. This therapy applies 100 ns long electric pulses 30 kV/cm in amplitude using a contact electrode and triggers apoptosis in the treated tissue. Here we review the progress that has been made in understanding the mechanisms and targets of nanosecond pulsed electric fields (nsPEF) when applied to cells and tissues. This work began in 2001 in the laboratory of Karl Schoenbach who collaborated with biologists Stephen Beebe and Stephen Buescher to demonstrate the permeabilization of intracellular organelles. Since then over 100 papers have been published studying the cellular responses to nsPEF. We discuss these targets and cellular responses and introduce some new results from our group using nanoelectroablation to treat human pancreatic carcinoma in a murine xenograft model system. We have determined that 500 pulses 100 ns long and 30 kV/cm in amplitude are sufficient to ablate human pancreatic carcinomas growing in immunosuppressed mice and these ablated tumors do not recur for at least 300 days. We have also determined that the reactive oxygen species generation that is triggered within a minute after nsPEF treatment is Ca2+-dependent. In order bring this therapy into the clinic for the treatment of human tumors we are developing both a pulse generator as well as delivery electrodes to target the tumors to be treated. We will describe the NanoBlate® Model NB-1 100 ns pulse generator and the first human clinical trial data using nanoelectroablation to ablate basal cell carcinomas without scarring.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2013; DOI:10.1117/12.2002538 · 0.20 Impact Factor