In this regard, Sensenig et al. conclude that, "Plasma-induced DNA damage in turn may lead to the observed plasma-induced apoptosis. Since plasma is non-thermal, it may be used to selectively treat malignancies" (2010, para. 4). The foregoing findings were also congruent with previous research by Kligman et al. (2007). According to these researchers, the floating electrode dielectric barrier discharge plasma (FE-DBD) plasma treatment has been found to invoke apoptosis in melanoma cancer cell lines, and it accomplishes this without causing necrosis while still possessing the ability to initiate apoptosis in the targeted cells (Kligman et al., 2007). The "floating" designation in this application is derived from the manner in which the plasma is generated. Simply put, the FE-DBD plasma treatment uses two electrodes, one of which is a dielectric-protected powered electrode and the other being an active electrode represented by mammalian tissue such as a human patient (Kligman et al., 2007).

While the first dielectric-protected powered electrode holds the capacity for the generation of the non-thermal plasma, it does not activate until the second electrode (i.e., a human patient) comes within close proximity. According to Kligman et al., "Discharge ignites when the powered electrode approaches the surface to be treated at a distance (discharge gap) less than about 3 mm, depending on the form, duration, and polarity of the driving voltage" (p. 4). Of special note for the destruction of undesirable cells such as cancers, these authors emphasize that this treatment regimen holds significant promise for the treatment of cancer through the invocation of apoptosis in the targeted cells. In this regard, these researchers conclude that, "Melanoma cells, treated by plasma at doses significantly below those required for cell destruction, survive the plasma treatment but develop apoptosis many hours post treatment and die (disintegrate) by themselves gracefully" (Kligman et al., 2007, p. 4).

Because the supporting non-thermal plasma technology is of fairly recent introduction, it is not surprising that more research in this area is needed to determine optimum plasma levels and durations of exposure, but the results of the Kligman et al. study and the others reviewed above all suggest that it may be possible to use non-thermal plasma treatments to accurately manipulate cellular activity in highly therapeutic ways that minimize or avoid many of the negative effects of current treatment regimens. As Kligman et al. conclude, "This could potentially be an intriguing new idea for cancer treatment, especially if by manipulation of plasma parameters the treatment could be made selective to cancerous cells over healthy cells, as was demonstrated before for bacteria vs. healthy cells" (2007, p. 4).

A recent study by Kim et al. (2010) also focused on the potential use of non-thermal atmospheric plasma treatment for cancer therapy by investigating the mechanism that is used by plasma to invoke anti-proliferative properties and cell death in human colorectal cancer cells. According to Kim et al., "Non-thermal atmospheric plasma induced cell growth arrest and induced apoptosis. In addition, plasma reduced cell migration and invasion activities. As a result, we found that plasma treatment to the cells increases ?-catenin phosphorylation, suggesting that ?-catenin degradation plays a role at least in part in plasma-induced anti-proliferative activity" (2010, p. 530). Based on these findings, Kim and his associates remove the speculative aspects that characterized previous studies and conclude outright that, "Non-thermal atmospheric plasma constitutes a new biologic tool with the potential for therapeutic applications that modulate cell signaling and function" (p. 530).

All of the foregoing studies generally involved the various effects of non-thermal plasma on mammalian cell activity and apoptosis with a specific focus on how these processes can be used to treat cancers. There appears to be an enormous range of treatment alternatives that need to be explored to identify optimum treatment parameters, but the findings that emerged from the research to date clearly indicate that non-thermal plasma represents a valuable tool in the...

A recurring theme that also emerged from the research, though, was the fact that non-thermal plasma therapies remain understudied. Given the potential benefits that could be gained from the therapeutic application of non-thermal plasma technologies and the staggering human and economic costs that are associated with current treatment protocols demands that these gaps in the existing body of knowledge be addressed, and these issues are discussed further below.
Identified Gaps in the Existing Body of Knowledge

The ability to create non-thermal plasma has created interest among a wide range of disciplines besides healthcare (Cleveland & Morris, 2006), but given the significant public health threat represented by cancer, this application appears to be one of the more promising for the immediate future. For instance, Di Quinzio, Dewar, Burge and Veugelers (2005) report that one of the more promising areas identified in the research for non-thermal plasma treatment, that of treating melanoma, is desperately needed today. According to these authorities, "Malignant melanoma is a deadly skin cancer with a rapidly increasing incidence, mortality and public health burden. The worldwide incidence of melanoma in 2000 was 2.4/100,000 for males and 2.21/100,000 for females. It is estimated that in 2003, there will be 54,200 new cases of melanoma and 7,600 consequent deaths in the U.S.; Canadian estimates for the same period are 3,900 new cases and 840 deaths" (p. 136). Therefore, in order to realize the full potential of non-thermal plasma technology in the determining its precise effects of non-thermal plasma on mammalian cell activity and apoptosis in ways that can help treat these and other types of cancer, the following gaps in the existing body of knowledge should be addressed:

1. Seek to better delineate the pathways that are triggered by sub-lethal plasma exposure (Kalghatgi, 2009).

2. Identify and assess the primary signaling components of the apoptotic pathway to determine the manner in which non-thermal plasma-induced effects result in cell apoptosis (Kalghati, 2009).

3. Identify relevant molecular arrays and real time programmed cell death target pathways and proteins that are involved in the cellular response to plasma exposure (Kalghati, 2009).

4. Investigate the actions of the various components of a plasma discharge to isolate the ultraviolet, the free radicals, and/or the charged particles (Kalghatgi, 2009).

5. Develop a better understanding concerning the precise interaction between plasma and living mammalian tissue as well as the physical and biochemical mechanisms that are involved (Kligman et al., 2007).