Over the past decade, cold atmospheric plasma (CAP), a near room temperature ionized gas has shown its promising application in cancer therapy. Two CAP devices, namely dielectric barrier discharge and plasma jet, show significantly anti-cancer capacity over dozens of cancer cell lines in vitro and several subcutaneous xenograft tumors in vivo. In contrast to conventional anti-cancer approaches and drugs, CAP is a selective anti-cancer treatment modality. Thus far establishing the chemical and molecular mechanism of the anti-cancer capacity of CAP is far from complete. In this review, we provide a comprehensive introduction of the basics of CAP, state of the art research in this field, the primary challenges, and future directions to cancer biologists.

To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demonstrated several principles to optimize the anti-cancer capacity of the CAPs media on glioblastoma cells and breast cancer cells. Specifically, using larger wells on a multi-well plate, smaller gaps between the plasma source and the media, and smaller media volume enabled us to obtain a stronger anti-cancer CAPs media composition without increasing the treatment time. Furthermore, cysteine was the main target of effective reactive species in the CAPs media. Glioblastoma cells were more resistant to the CAPs media than breast cancer cells. Glioblastoma cells consumed the effective reactive species faster than breast cancer cells did. In contrast to nitric oxide, hydrogen peroxide was more likely to be the effective reactive species.

Selectively treating tumor cells is the ongoing challenge of modern cancer therapy. Recently, cold atmospheric plasma (CAP), a near room-temperature ionized gas, has been demonstrated to exhibit selective anticancer behavior. However, the mechanism governing such selectivity is still largely unknown. In this review, the authors first summarize the progress that has been made applying CAP as a selective tool for cancer treatment. Then, the key role of aquaporins in the H2O2 transmembrane diffusion is discussed. Finally, a novel model, based on the expression of aquaporins, is proposed to explain why cancer cells respond to CAP treatment with a greater rise in reactive oxygen species than homologous normal cells. Cancer cells tend to express more aquaporins on their cytoplasmic membranes, which may cause the H2O2 uptake speed in cancer cells to be faster than in normal cells. As a result, CAP treatment kills cancer cells more easily than normal cells. Our preliminary observations indicated that glioblastoma cells consumed H2O2 much faster than did astrocytes in either the CAP-treated or H2O2-rich media, which supported the selective model based on aquaporins.

Previous research in cold atmospheric plasma (CAP) and cancer cell interaction has repeatedly proven that the cold plasma induced cell death. It is postulated that the reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a major role in the CAP cancer therapy. In this paper, we seek to determine a mechanism of CAP therapy on glioblastoma cells (U87) through an understanding of the composition of the plasma, including treatment time, voltage, flow-rate and plasma-gas composition. In order to determine the threshold of plasma treatment on U87, normal human astrocytes (E6/E7) were used as the comparison cell line. Our data showed that the 30 sec plasma treatment caused 3-fold cell death in the U87 cells compared to the E6/E7 cells. All the other compositions of cold plasma were performed based on this result: plasma treatment time was maintained at 30 s per well while other plasma characteristics such as voltage, flow rate of source gas, and composition of source gas were changed one at a time to vary the intensity of the reactive species composition in the plasma jet, which may finally have various effect on cells reflected by cell viability. We defined a term “plasma dosage” to summarize the relationship of all the characteristics and cell viability.

Cold atmospheric plasma (CAP) has just recently been showing promising anti-cancer activities supported by ability to induce cell death via apoptosis and cell cycle arrest leading to tumor cell destruction in vitro, and in vivo. Several studies showed the ability of CAP-activated media to modulate the tumor cell environment a link between the generation of reactive oxygen species/reactive nitrogen species and cancer cell death following CAP treatment. Targeting cancer cells through ROS-mediated mechanisms has become an attractive strategy for effective and selective cancer treatment by exploiting the aberrant redox characteristics of cancer cells. These effects support the potential direct (CAP) and indirect (CAP-activated media) applications for adjuvant anti-cancer therapeutics, in a combination with the chemo-, radio-, and nano-therapies.

Neurenteric cysts account for 0.7-1.3% of spinal axis tumors. These rare lesions result from the inappropriate partitioning of the embryonic notochordal plate and presumptive endoderm during the third week of human development. Heterotopic rests of epithelium reminiscent of gastrointestinal and respiratory tissue lead to eventual formation of compressive cystic lesions of the pediatric and adult spine. Histopathological analysis of neurenteric tissue reveals a highly characteristic structure of columnar or cuboidal epithelium with or without cilia and mucus globules. Patients with symptomatic neurenteric cysts typically present in the second and third decades of life with size-dependent myelopathic and/or radicular signs. Magnetic resonance imaging and computed tomography are essential diagnostic tools for the delineation of cyst form and overlying osseous architecture. A variety of approaches have been employed in the treatment of neurenteric cysts each with a goal of total surgical resection. Although long-term outcome analyses are limited, data available indicate that surgical intervention in the case of neurenteric cysts results in a high frequency of resolution of neurological deficit with minimal morbidity. However, recurrence rates as high as 37% have been reported with incomplete resection secondary to factors such as cyst adhesion to surrounding structure and unclear dissection planes. Here we present a systematic review of English language literature from January 1966 to December 2009 utilizing MEDLINE with the following search terminology: neurenteric cyst, enterogenous cyst, spinal cord tumor, spinal dysraphism, intraspinal cyst, intramedullary cyst, and intradural cyst. In addition, the references of publications returned from the MEDLINE search criteria were surveyed in order to examine other pertinent reports.

Object This study details long-term clinical and radiographic outcomes following single-level posterior cervical foraminotomy for degenerative disc or osteophyte disease. Methods The authors conducted a retrospective review of 162 cases involving patients treated by a single surgeon using a posterior cervical foraminotomy. Inclusion criteria were a minimum of 5 years' clinical and radiographic follow-up and unilateral single-level posterior cervical foraminotomy for degenerative disease between C-3 and C-7. Patients who had undergone previous operations, those who underwent bilateral procedures, and those who underwent foraminotomy as part of a larger laminectomy were excluded. The Neck Disability Index (NDI) was used for clinical follow-up, and radiographic follow-up was performed using static and dynamic lateral radiographs to compare focal and segmental alignment and changes in disc-space height. Results The mean presenting NDI score was 18 (range 2–39). The most common presenting symptoms were radiculopathy (110 patients [68%]), neck pain (85 patients [52%]), and subjective weakness (91 patients [56%]). The mean preoperative focal angulation at the surgically treated level was 4.2° (median 4.1°, range 7.3–15.3°), and the mean preoperative segmental curvature between C-2 and C-7 was 18.0° (median 19.3°, range −22.1 to 39.3°). The mean postoperative NDI score was 8 (range 0–39). Improvement in NDI scores was seen in 150 patients (93%). Resolution of radiculopathy was experienced by 104 patients (95% of patients with radiculopathy). The mean radiographic follow-up was 77.3 months (range 60–177 months). No statistically significant changes in focal or segmental kyphosis or disc-space height were seen among the overall cohort with time (Cox proportional hazards analysis and Student t-test, p > 0.05). The mean postoperative focal angulation was 4.1° (median 3.9°, range −9.9° to 15.1°) and mean postoperative segmental angulation was 17.6° (median 15.4°, range −40.2 to 35.3°). Postoperative instability on dynamic imaging was present in 8 patients (4.9%); 7 of these patients were clinically asymptomatic and were treated conservatively, and 1 required cervical fusion. Postoperative loss of lordosis (defined as segmental Cobb angle < 10°) was seen in 30 patients (20%), 9 of whom had clinical symptoms and 4 of whom required further surgical correction. Factors associated with worsening sagittal alignment (Cox proportional hazards analysis, p < 0.05) included age > 60 at initial surgery, the presence of preoperative cervical lordosis of < 10°, and the need for posterior surgery after the initial foraminotomy Conclusions The posterior cervical foraminotomy is highly effective in treating patients with cervical radiculopathy and results in long-lasting pain relief and improved quality-of-life outcomes in most patients. Long-term radiographic follow-up shows no significant trend toward kyphosis, although select patient subsets (patients older than 60 years, patients who had previous posterior surgery, and patients with < 10° of lordosis preoperatively) appear to be at higher risk and require closer follow-up.

Over past several years, the cold plasma-stimulated medium (PSM) has shown its remarkable anti-cancer capacity in par with the direct cold plasma irradiation on cancer cells or tumor tissues. Independent of the cold plasma device, PSM has noticeable advantage of being a flexible platform in cancer treatment. Currently, the largest disadvantage of PSM is its degradation during the storage over a wide temperature range. So far, to stabilize PSM, it must be remained frozen at −80 °C. In this study, we first reveal that the degradation of PSM is mainly due to the reaction between the reactive species and specific amino acids; mainly cysteine and methionine in medium. Based on this finding, both H2O2 in PSM and the anti-cancer capacity of PSM can be significantly stabilized during the storage at 8 °C and −25 °C for at least 3 days by using phosphate-buffered saline (PBS) and cysteine/methionine-free Dulbecco’s Modified Eagle Medium (DMEM). In addition, we demonstrate that adding a tyrosine derivative, 3-Nitro-L-tyrosine, into DMEM can mitigate the degradation of PSM at 8 °C during 3 days of storage. This study provides a solid foundation for the future anti-cancer application of PSM.