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Tools that reduce the number of surgical biopsies performed on benign skin lesions have the potential to improve patient care. The non-invasive pigmented lesion assay (PLA) gene expression test is such a tool. It helps rule out melanoma and the need for surgical biopsies of atypical pigmented skin lesions with a NPV >99%. Analyses of ∼15,000 PLA samples in the real-world routine use setting of over 600 US dermatology offices demonstrated that 87% were PLA(-). A real-world utility study in 381 cases demonstrated that 99% of PLA(-) cases were monitored, while all PLA(+) cases were surgically biopsied demonstrating that clinicians follow the guidance of the test.
Post-inflammatory hyperpigmentation (PIH) occurs following various types of skin inflammation such as acne and scars. Recently, it was reported that not only inflammation factors from the epidermis but also dermal fibroblast-derived factors contribute to the process of PIH associated with disruption of the dermal epidermal junction. However, laser treatments are usually chosen as a clinical remedy rather than topical medicine. This is because the most common targets of whitening agents are focused on epidermal events after UV-irradiation such as the production and accumulation of melanin and turnover delays.
Melanocytes in the basal layer of the epidermis produce the pigment melanin in cytoplasmic organelles known as melanosomes. Melanosomes are transferred to keratinocytes which provide the color in our skin. Recently Diwakar et al. reported crucial roles of protein glycosylation in both melanogenesis and melanosome transfer to keratinocytes and each was inhibited by the nucleoside cytidine. In this study, the in-vitro efficacy of cytidine was evaluated in comparison with ascorbyl glucoside (AA2G), Kojic acid (positive control) and vehicle (negative) control by using a commercially available co-cultured tissue pigmentation model (MelanoDerm™).
Ocular melanoma (OM) is the most common primary intraocular malignancy. To determine trends in incidence and geographical distribution of OM cases in Canada, we conducted the first comprehensive, population-based study of OM in all Canadian provinces and territories during 1992-2010. We examined patient clinical characteristics and incidence trends of OM by analyzing two independent population-based databases (Canadian Cancer Registry and Le Registre Québécois du Cancer) using corresponding ICD-O-3 and ICD-10 codes for all histological subtypes of OM and for all primary sites of origin in the eye including the uvea and conjunctiva.
There is an increasing awareness that environmental factors, such as UV radiation, cigarette smoke, smog, industrial pollution, have negative impacts on skin and lead to premature aging, and in some case even skin cancer. Previous studies have shown that one of the negative actions from UV radiation is to cause DNA damage, such as cyclobutane pyrimidine dimers (CPD). Nucleotide excision repair (NER) has been shown to be critical for the repair of CPDs, and the excision repair cross-complementation group1 (ERCC1) has been found to be one of the rate-limiting enzymes in the NER pathway.
Background: Gasdermin C (GSDMC) is known to be a member of GSDM family genes and to be expressed in the epithelial cells of various tissues including the skin. Recently, it has been shown that GSDMC is induced by ultraviolet (UV) irradiation and contributes to UV-induced MMP-1 expression in human skin keratinocytes. However, how UV irradiation induces GSDMC expression remains unclear. Objective: We aimed to investigate the role of TRPV1 in UV-induced GSDMC expression and the signaling pathways involved in the process in HaCaT cells.
Circadian clock critically influences mast cell (MC) functions and thereby drives the daily rhythms in IgE/MC–mediated allergic reactions. In human skin, these clocks may be regulated by cryptochromes (CRYs) and opsins (OPNs) - photoreceptors (PRs), which were recently identified in a number of human cutaneous cells. Here we report on the expression of several OPNs and CRYs in human MCs. Data were collected on freshly isolated and on cultured cutaneous MCs from several body locations; cultured CD34-positive peripheral blood stem cell-derived MCs (PSCMCs); and LAD2-MCs.
Ultra-weak photon emission (UPE), often termed biophoton emission, is observed in a wide range of living organisms. This phenomenon is associated with the oxidative state of lipids, proteins, and cells. UPE from human skin increases following UV exposure, but mechanisms underpinning this phenomenon remain poorly understood. In this study, we firstly, assessed UPE from ex vivo human skin. Following spectral pattern analysis of UV-generated UPE using a polychromatic spectrum analysis system, we performed UPE imaging using a CCD camera system.
Currently, the American Academy of Dermatology (ADD) guidelines rank their recommended treatments for acne vulgaris via lettered grading system with “A” (highest recommendation) to “C” (lowest). This study aims to investigate if AAD recommendations for over the counter (OTC) topical acne treatments are coherent with patients’ behaviors. Public knowledge and adherence of the recommended over the counter (OTC) topical treatments for acne was analyzed using Google Trends. This online database generates relative search frequency (RSF) data, on a scale of 0-100, based on users’ selected terms.
Oxidative stress induced by reactive oxygen species (ROS) plays an important role in the process of intrinsic and extrinsic aging of the skin. Previous research has shown that ROS trigger and contribute to skin aging manifesting in wrinkles, altered pigmentation, and uneven skin tone. The main source of ROS production is intracellular mitochondria. Extrinsic factors, including solar radiation and pollution, can also stimulate ROS development within skin. We have developed a new topical product combining a unique blend of antioxidants that induces cellular antioxidant defense mechanisms that are crucial for prevention and repair of cell damage caused by oxidative stress.
Atopic dermatitis (AD) is the most common inflammatory disease of the skin characterized by defects in keratinocyte differentiation and skin barrier dysfunction. Despite its prevalence, an in vitro,commercial model of AD is not currently available to facilitate basic research and therapeutic development. Using the reconstructed full thickness human epidermal model (EpiDermFT), an inflammatory cocktail comprised of Th2 cytokines was used to induce changes to mimic an atopic dermatitis phenotype. Following treatment with IL-4, IL-13 and IL-31, significant changes in several markers of differentiation and skin barrier integrity were observed, closely resembling AD skin.
Every day our skin is exposed to a wide range of environmental aggressors that are known to accelerate extrinsic aging of the skin. These include ultraviolet (UV) rays and pollution in the form of smoke, ozone, and particulate matter. Recent studies indicate that high energy visible light (HEV) and infrared-A radiation (IRA) can also induce damage of skin resulting in premature skin aging. We have developed a product (LV-D) for biological protection containing a combination of antioxidants, plant extracts, and peptides, that demonstrates multifactorial protection against a variety of environmental aggressors.
TNF- alpha inhibitors, etanercept (E), adalimumab (A), and infliximab (I), include an indication for the treatment of moderate-to-severe psoriasis and have emerged as an important, and widely used class of drugs. Notably, the incidences of adverse events (AEs) occurring during exposure to these biologic agents are rarely stratified by sex in published trials and are not described in the Full Prescribing Information for each drug. To address this, we conducted a review of literature to determine rates of reported AEs by sex for E, A and I in psoriasis-based randomized clinical trials.
Management of psoriasis comprises a variety of treatment options such as topical treatments (e.g. local applications of corticosteroid, tazarotene or vitamin D analogues), UV therapies, oral treatments (e.g. methotrexate, acitretin, cyclosporine, or apremilast), and intravenous biological treatments (anti-TNFα and anti-IL-12/23 antibodies). Most of these treatments can cause severe side effects, therefore safer treatment modalities would be valuable in the management of psoriasis. Topical and oral treatments, as well as UV therapies generally constitute a first line of treatments.
Apremilast is a novel, orally deliverable small molecule that specifically targets phosphodiesterase-4 (PDE4) and therefore modulates the expression of a network of proinflammatory and anti-inflammatory mediators implicated in psoriasis. The efficacy has been demonstrated in multiple Phase III clinical trials and is currently used for the treatment of patients with moderate to severe plaque psoriasis. Even though the efficacy of Apremilast has been clinically demonstrated, little is known about the mechanism by which Apremilast modulates the immune system in psoriasis.
Targeting IL17 is now an established approach for the treatment of psoriasis. As a key player in this pathway, RORγ has become a major target for the industry leading to a series of new compounds reaching the clinic, with VTP-43742 and GSK2981278 leading the way for oral and topical treatment respectively. As part of our ongoing research on RORγ inverse agonists as new modalities to treat psoriasis, we set out to find compounds highly compatible with topical administration. Starting from known competitor compounds and from our own published assets, the design focused on optimizing the predicted flux through skin while maintaining high potency.
Cutaneous delivery of therapeutic compounds is severely limited by the skin’s stratum corneum barrier. This limitation creates significant unmet needs, especially in dermatology, for drug delivery systems that increase skin permeability. Herein, STAR particles are presented as a novel, platform technology capable of dramatically enhancing delivery of topical therapies to skin in a manner that is simple-use, low-cost, minimally invasive, safe and effective across a broad range of bioactive agents.
We have recently developed a novel computational drug discovery system (DrugPredict) that simultaneously performs in silico target-based and phenotypic screening on half a million compounds. We have previously applied DrugPredict to identify repurposed candidate drugs for ovarian cancer and experimentally validated that a commonly prescribed pain medication can be used to kill ovarian cancer cells. In the current study, we retargeted DrugPredict to identify repurposed drug candidates for the dermatologic condition psoriasis.
The efficacy of SNA-125, a first-in-class topical selective kinase inhibitor (including JAK3/TrkA) with low systemic exposure, was evaluated in the imiquimod (IMQ)-induced mouse model of psoriasis (PSO). IMQ 5% cream (Aldara™) was applied once daily for 10 days on ears and shaved backs to induce PSO. SNA-125 (5% or 10%) or vehicle (25% transcutol P; 75% propylene glycol) was applied twice daily to ears and backs (2 and 8 hrs post-IMQ) for 10 days, while the positive control was applied once daily (clobetasol 0.05%; 2 hrs post-IMQ).
Skin cancer is the most common type of cancer worldwide. Both prevention and protection against skin cancer is a global issue, and an advanced therapy with convenient accessibility and low side effects would be in high demand. In an effort to discover anticancer agents, we identified a novel tubulin inhibitor STK899704, which structure is distinct from other microtubule-binding agents such as colchicine, vinca alkaloids, and taxanes. STK899704 inhibited microtubule polymerization leading to the cell cycle arrest at mitosis, and repressed the proliferation of cancer cell lines from various origins.