Alessia Pacifico

Fate of UVB-induced p53 mutations in SKH-hr1 mouse skin after discontinuation of irradiation: relationship to skin cancer development

Chronic exposure to ultraviolet (UV) radiation causes skin cancer in humans and mice. We have previously shown that in hairless SKH-hr1 mice, UVB-induced p53 mutations arise very early, well before tumor development. In this study, we investigated whether discontinuation of UVB exposure before the onset of skin tumors results in the disappearance of p53 mutations in the skin of hairless SKH-hr1 mice. Irradiation of mice at a dose of 2.5 kJ/m2 three times a week for 8 weeks induced p53 mutations in the epidermal keratinocytes of 100% of the mice. UVB irradiation was discontinued after 8 weeks, but p53 mutations at most hotspot codons were still present even 22 weeks later. During that period, the percent of mice carrying p53V154A/R155C, p53H175H/H176Y, and p53R275C mutant alleles remained at or near 100%, whereas the percentage of mice with p53R270C mutation decreased by 45%. As expected, discontinuation of UVB after 8 weeks resulted in a delay in tumor development. A 100% of tumors carried p53V154A/R155C mutant alleles, 76% carried p53H175H/H176Y mutants, and 24 and 19% carried p53R270C and p53R275C mutants, respectively. These results suggest that different UVB-induced p53 mutants may provide different survival advantages to keratinocytes in the absence of further UVB exposure and that skin cancer development can be delayed but not prevented by avoidance of further exposure to UVB radiation.

Short contact therapy with tazarotene in psoriasis vulgaris

Background: We present the results of a multicentre, not controlled, clinical study on the tolerability and efficacy of tazarotene gel, used as short contact therapy (SCT), in psoriasis vulgaris. Objective: To evaluate whether irritant contact dermatitis caused by tazarotene was less frequent and/or less severe with SCT than with traditional therapy, and whether SCT with tazarotene was as effective as traditional therapy. Methods: Forty-three patients with plaque psoriasis were treated by SCT with 0.1% tazarotene gel (once daily application for 20 min, followed by washing with water). Treatment duration was 45 days. Results: Irritant contact dermatitis caused by tazarotene used as SCT was much less frequent and severe than traditional treatment with the same drug. SCT with tazarotene was effective in the treatment of plaque psoriasis. Conclusion: Tazarotene, used as SCT, was better tolerated than the same drug used as traditional treatment. Furthermore, SCT appeared to be as effective as traditional therapy with the same drug.

A new formulation of an occlusive dressing containing betamethasone valerate 0.1% in the treatment of mild to moderate psoriasis

Background  Betamethasone valerate (BMV) is a medium‐potency corticosteroid commonly used for the treatment of chronic psoriasis. Although occlusion has been shown to enhance the efficacy of BMV treatment, no ready‐to‐use occlusive BMV formulation is currently approved for the market.

Molecular Basis of Skin Carcinogenesis

p53 tumor suppressor gene is the most commonly mutated gene in human and mouse cancers. Disruption of the p53 and Rb pathways is a fundamental property of most human cancer cells. Inactivation of CDKN2A can lead to deregulation of these two pathways. Genetic abnormalities in CDKN2A gene have been well documented in human melanoma but their involvement in human non-melanoma skin cancer (NMSC) is less clear. Several studies have shown that NMSC harbor unique mutations in the p53 gene as well as inactivation of the CDKN2A gene. While mutations in the p53 gene are induced by UV radiation and represent tumor-initiating events, the majority of alterations detected in the CDKN2A gene do not appear to be UV-dependent. In conclusion, in addition to p53 mutations, silencing of other tumor suppressor genes such as the CDKN2A gene might play a significant role in NMSC development.