The Development of Nonthermal Plasma and Tirapazamine as a Novel Combination Therapy to Treat Melanoma In Situ.

Although melanoma accounts for only 5.3% of skin cancer, it results in >75% of skin-cancer-related deaths. To avoid disfiguring surgeries on the head and neck associated with surgical excision, there is a clear unmet need for other strategies to selectively remove cutaneous melanoma lesions. Mohs surgery is the current treatment for cutaneous melanoma lesions and squamous and basal cell carcinoma. While Mohs surgery is an effective way to remove melanomas in situ, normal tissue is also excised to achieve histologically negative margins. This paper describes a novel combination therapy of nonthermal plasma (NTP) which emits a multitude of reactive oxygen species (ROS) and the injection of a pharmaceutical agent. We have shown that the effects of NTP are augmented by the DNA-damaging prodrug, tirapazamine (TPZ), which becomes a free radical only in conditions of hypoxemia, which is often enhanced in the tumor microenvironment. In this study, we demonstrate the efficacy of the combination therapy through experiments with B16-F10 and 1205 Lu metastatic melanoma cells both in vitro and in vivo. We also show the safety parameters of the therapy with no significant effects of the therapy when applied to porcine skin. We show the need for the intratumor delivery of TPZ in combination with the surface treatment of NTP and present a model of a medical device to deliver this combination therapy. The importance of functional gap junctions is indicated as a mechanism to promote the therapeutic effect. Collectively, the data support a novel therapeutic combination to treat melanoma and the development of a medical device to deliver the treatment in situ.

A 2-month post-COVID-19 follow-up study on patients with dyspnea.

BACKGROUND AND AIMS: Dyspnea is one of the most common symptoms associated with the COVID-19 caused by novel coronavirus SARS-CoV-2. This study aimed to assess the prevalence of dyspnea, observe co-variables, and find predictors of dyspnea after 2 months of recovery from COVID-19. METHODS: A total of 377 patients were included in the study based on their responses and clinical findings during initial admission to the hospital with COVID-19. After excluding five deceased patients, a total of 327 patients were interviewed through telephone using a 12-point dyspnea scale and using relevant questions to gauge the patient clinically. Interviews were carried out by trained physicians, and responses were recorded and stored. All analyses were carried out using the statistical programming language R. RESULTS: Of the total 327 participants in the study, 34% had stated that they were suffering from respiratory symptoms even after 2 months of COVID-19. The study demonstrated that patient oxygen saturation level SpO2 (P = .03), D-dimer (P = .001), serum ferritin (P = .006), and the presence and severity of dyspnea are significantly correlated. In addition to that, patient smoking history (P = .012) and comorbidities such as chronic obstructive pulmonary disease (COPD) (P = .021) were found to be statistically significant among groups. CONCLUSION: These findings of this study can be useful for predicting and managing long-term complications of COVID-19.

DNA methylation inhibitors: Retrospective and perspective view.

DNA methylation is an epigenetic modification that contributes to essential biological processes such as retrotransposon silencing, cell differentiation, genomic imprinting and X-chromosome inactivation. DNA methylation generates a stable epigenetic mark associated with silencing of gene expression. Aberrant DNA methylation is associated with the development of different tumor types. Reversing DNA methylation is a rational strategy to restore gene re-expression and induce cell differentiation in cancer. DNA hypomethylating agents is a class of drugs that demonstrated efficacy in different tumors. In this chapter, the classification of DNA hypomethylating agents, their pharmacodynamics and their potential drawbacks will be discussed.