Pulse Power Ablation of Melanoma with Nanosecond Pulsed Electric Fields

Abstract

Melanocytes are cells that originate in the neural crest. In the dermis, their well characterized role is to produce melanin and through interactions with keratinocytes transfer this pigment to determine skin color and protect the largest organ in the body, the skin, from ultraviolet light. As an effective free radical scavenger, melanin protects against reactive oxygen species that would otherwise damage DNA [Rozanowska et al., 1999]. Melanocytes may also have other roles such as immune, neuroendocrine, and signaling functions through interactions with cells other than keratinocytes, such as lymphocytes, mast cells and endothelial cells [see Tsatmali et al., 2002 for review]. However, keratinocytes regulate melanocyte number, differentiation and melanin production in response to UV radiation. It may be that the resilience of melanocytes to protect the skin, their extraordinary regenerative capacity and their origin as neural crest migratory cells makes them one of the most deadly forms of metastatic skin cancers when they undergo tumorogenesis. It is known that there is a great deal of common cellular and genetic events among embryonic development, tissue regeneration and cancer. Further, typical self-renewal and migration capacity of cancer are shared with embryonic and regenerative cells [White and Zon, 2008]. The recapitulation of embryonic genetic programs is facilitated by overexposure to extreme sunlight (UVA and UVB) or tanning bed light (mostly UVA). The American Cancer Society estimated that in the US in 2009, 68,720 new cases of melanoma (188 new cases /day) will be diagnosed and 8,650 people will die from the disease (24 melanoma deaths /day). The continued increase in melanoma is a significant cause of morbidity and mortality in the Western world. Thus, metastatic melanoma remains a persistent therapeutic challenge. There are limited successes in preventing this often fatal disease and there are even fewer successes in developing a cure.