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Introduction: Nonthermal atmospheric pressure plasma (NTAPP) therapy has emerged as a promising modality in dermatology for wound healing, tissue regeneration, and anti-tumor applications. This study evaluated the feasibility and effectiveness of a simple, one-week NTAPP treatment protocol in the SKH1 hairless mouse model of chronic ultraviolet (UV) radiation-induced carcinogenesis. Materials and methods: SKH1 mice were exposed to solar-simulated UV light 5 times a week for 10 weeks, which produced multiple skin tumors on each mouse. At week 25 NTAPP treatment was administered to a subgroup of mice at a setting of 20 kV with a 20 ns pulse width and 200 Hz frequency three times within a single week. A total of 31 NTAPP-treated and 34 internal control tumors (i.e., nearby tumors on the same mouse) in UV-exposed, NTAPP-treated mice were evaluated for tumor size at 0 and 28 days after the beginning of the treatment by using ImageJ on standardized photographs. A subset of the tumors was also assessed with a 33 MHz high-frequency ultrasound (HFUS) to measure vertical tumor thickness. In similarly housed control mice, sizes of 64 tumors were evaluated as external controls. Results: NTAPP induced a significant reduction in the mean tumor area from 5.65 ± 6.51 mm² before treatment to 1.74 ± 3.99 mm² 28 days post-treatment (paired t-test, p = 0.0016). Internal control tumors, in contrast, showed an increase in area from 3.24 ± 2.54 mm² before treatment to 4.57 ± 3.58 mm² 28 days post-treatment (paired t-test, p = 0.0296). Of the 31 treated tumors, 23 completely disappeared; in contrast, only six non-treated internal control tumors disappeared (p = 0.0139, two-sided chi-square test). Simultaneously, optically guided HFUS revealed a significant decrease in tumor thickness in treated areas (paired t-test, p = 0.0006), with no significant changes observed in the internal control tumors (paired t-test, p = 0.5555). External control tumors showed an increase in size, which was not statistically significant. Discussion: The results demonstrated that a one-week NTAPP protocol could effectively eliminate 74 % of mouse tumors induced by UV radiation. These findings warrant further investigations of short, clinically feasible NTAPP treatment protocols for early skin cancer treatment.

Photosensitivity to structurally diverse drugs is a common but under-reported adverse cutaneous reaction and can be classified as phototoxic or photoallergic. Phototoxic reactions occur when the skin is exposed to sunlight after administering topical or systemic medications that exhibit photosensitizing activity. These reactions depend on the dose of medication, degree of exposure to ultraviolet light, type of ultraviolet light, and sufficient skin distribution volume. Accurate prediction of the incidence and phototoxic response severity is challenging due to a paucity of literature, suggesting that phototoxicity may be more frequent than reported. This paper reports an extensive literature review on phototoxic drugs; the review employed pre-determined search criteria that included meta-analyses, systematic reviews, literature reviews, and case reports freely available in full text. Additional reports were identified from reference sections that contributed to the understanding of phototoxicity. The following drugs and/or drug classes are discussed: amiodarone, voriconazole, chlorpromazine, doxycycline, fluoroquinolones, hydrochlorothiazide, nonsteroidal anti-inflammatory drugs, and vemurafenib. In reviewing phototoxic skin reactions, this review highlights drug molecular structures, their reactive pathways, and, as there is a growing association between photosensitizing drugs and the increasing incidence of skin cancer, the consequential long-term implications of photocarcinogenesis.

The documentation of the change in the number and appearance of pigmented cutaneous lesions over time is critical to the early detection of skin cancers and may provide preliminary signals of efficacy in early-phase therapeutic prevention trials for melanoma. Despite substantial progress in computer-aided diagnosis of melanoma, automated methods to assess the evolution of lesions are relatively undeveloped. This report describes the development and narrow validation of mathematical algorithms to register nevi between sequential digital photographs of large areas of skin and to align images for improved detection and quantification of changes. Serial posterior truncal photographs from a pre-existing database were processed and analyzed by the software, and the results were evaluated by a panel of clinicians using a separate Extensible Markup Language‒based application. The software had a high sensitivity for the detection of cutaneous lesions as small as 2 mm. The software registered lesions accurately, with occasional errors at the edges of the images. In one pilot study with 17 patients, the use of the software enabled clinicians to identify new and/or enlarged lesions in 3‒11 additional patients versus the unregistered images. Automated quantification of size change performed similarly to that of human raters. These results support the further development and broader validation of this technique.

Lineage-specific regulation of tumor progression by the same transcription factor is understudied. We find that levels of the FOXQ1 transcription factor, an oncogene in carcinomas, are decreased during melanoma progression. Moreover, in contrast to carcinomas, FOXQ1 suppresses epithelial-to-mesenchymal transition, invasion, and metastasis in melanoma cells. We find that these lineage-specific functions of FOXQ1 largely depend on its ability to activate (in carcinomas) or repress (in melanoma) transcription of the N-cadherin gene (CDH2). We demonstrate that FOXQ1 interacts with nuclear β-catenin and TLE proteins, and the β-catenin/TLE ratio, which is higher in carcinoma than melanoma cells, determines the effect of FOXQ1 on CDH2 transcription. Accordingly, other FOXQ1-dependent phenotypes can be manipulated by altering nuclear β-catenin or TLE proteins levels. Our data identify FOXQ1 as a melanoma suppressor and establish a mechanism underlying its inverse lineage-specific transcriptional regulation of transformed phenotypes.