Superoxide dismutase 1 (SOD1) is an abundant copper/zinc enzyme found in the cytoplasm that converts superoxide into hydrogen peroxide and molecular oxygen. Tetrathiomolybdate (ATN-224) has been recently identified as an inhibitor of SOD1 that attenuates FGF-2-and VEGF-mediated phosphorylation of ERK1/2 in endothelial cells. However, the mechanism for this inhibition was not elucidated. Growth factor (GF) signaling elicits an increase in reactive oxygen species (ROS), which inactivates protein tyrosine phosphatases ( angiogenesis ͉ cancer ͉ redox ͉ tetrathiomolybdate ͉ ATN-224

SummaryBackground/purpose: Sunscreens are believed to be a valuable tool in providing photoprotection against the detrimental effects of UV radiation, a known carcinogen. However, a number of controversies have developed regarding their safety and efficacy. This review summarizes the relevant studies surrounding these controversies. Methods: Evidence of the prevention of skin cancer, an oft-cited reason for sunscreen use, was examined as it pertains to squamous cell carcinoma, basal cell carcinoma and melanoma. We also reviewed studies examining the effects of sunscreen on the synthesis of vitamin D, an essential nutrient whose role in health and disease continues to grow. Lastly, we analyzed studies surrounding the safety and toxicity of oxybenzone, retinyl palmitate and nanoparticles of zinc oxide (ZnO) and titanium dioxide (TiO 2 ). Results: The overwhelming majority of available data is drawn from studies conducted using antiquated sunscreen formulations. Nonetheless, our research revealed that topical use of sunscreen protects against squamous cell carcinoma, does not cause vitamin D deficiency/ insufficiency in practice and has not been demonstrated to adversely affect the health of humans. Conclusion: Given the established benefits of UV protection, the use of sunscreens remains an important part of an overall photoprotective strategy. Future sunscreens with improved formulation should ideally offer superior protection. With increased usage of sunscreen by the public, continuous and vigilant monitoring of the overall safety of future products is also needed.

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Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development.

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Background Junctional (flat) naevi predominate on the extremities whereas dermal (raised) naevi are primarily found on the head, neck, and trunk. Few studies have investigated the anatomic site prevalence of melanocytic naevi categorized using dermoscopy. Objectives To identify the prevalence of dermoscopic patterns and structures of naevi from the back and legs of adolescents. Methods Dermoscopic images of melanocytic naevi were obtained from the back and legs of students from a population-based cohort in Framingham, Massachusetts. Naevi were classified into reticular, globular, homogenous, or complex dermoscopic patterns. Multinomial logistic regression modeling assessed the associations between dermoscopic pattern and anatomic location. Results A total of 509 participants (mean age 14 years) contributed 2,320 back naevi and 637 leg naevi. Compared to homogeneous naevi, globular and complex naevi were more commonly observed on the back than the legs (OR=29.39, 95% CI 9.53-90.65, p<0.001 and OR=6.8, 95% CI 2.7-17.14, p<0.001, respectively), whereas reticular lesions were less likely to be observed on the back than the legs (OR=0.67, 95% CI 0.54-0.84, p=0.001). Naevi containing any globules were more prevalent on the back than the legs (25% v. 3.6%, p<0.001). Naevi containing any network were more prevalent on the legs than the back (56% v. 40.6%, p<0.001). Conclusions These findings add to a robust body of literature suggesting that dermoscopically defined globular and reticular naevi represent biologically distinct naevus subsets that differ in histopathologic growth pattern, age- and anatomic-site related prevalence, molecular phenotype, and aetiologic pathways.

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Adequate photoprotection plays a paramount role in reducing the burden of both photoaging and photocarcinogenesis. The scope of photoprotective strategies employed by the public, from most to least effective, includes: sun avoidance, seeking shade, the use of protective clothing, and the application of sunscreen. Among these options, sunscreen use remains the strategy most frequently employed by the public--a reversal of the preferred order of photoprotection. Given this trend, it is clear why sunscreens invariably take center stage in any discussion regarding obtaining adequate photoprotection.