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Current Perspectives on the Role of Matrix Metalloproteinases in the Pathogenesis of Basal Cell Carcinoma.
Tampa, M, Georgescu, SR, Mitran, MI, Mitran, CI, Matei, C, Caruntu, A, Scheau, C, Nicolae, I, Matei, A, Caruntu, C, et al
Biomolecules. 2021;(6)
Abstract
Basal cell carcinoma (BCC) is the most common skin malignancy, which rarely metastasizes but has a great ability to infiltrate and invade the surrounding tissues. One of the molecular players involved in the metastatic process are matrix metalloproteinases (MMPs). MMPs are enzymes that can degrade various components of the extracellular matrix. In the skin, the expression of MMPs is increased in response to various stimuli, including ultraviolet (UV) radiation, one of the main factors involved in the development of BCC. By modulating various processes that are linked to tumor growth, such as invasion and angiogenesis, MMPs have been associated with UV-related carcinogenesis. The sources of MMPs are multiple, as they can be released by both neoplastic and tumor microenvironment cells. Inhibiting the action of MMPs could be a useful therapeutic option in BCC management. In this review that reunites the latest advances in this domain, we discuss the role of MMPs in the pathogenesis and evolution of BCC, as molecules involved in tumor aggressiveness and risk of recurrence, in order to offer a fresh and updated perspective on this field.
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Daily Lifestyle and Cutaneous Malignancies.
Sawada, Y, Nakamura, M
International journal of molecular sciences. 2021;(10)
Abstract
Daily lifestyle is a fundamental part of human life and its influence accumulates daily in the human body. We observe that a good daily lifestyle has a beneficial impact on our health; however, the actual effects of individual daily lifestyle factors on human skin diseases, especially skin cancers, have not been summarized. In this review, we focused on the influence of daily lifestyle on the development of skin cancer and described the detailed molecular mechanisms of the development or regulation of cutaneous malignancies. Several daily lifestyle factors, such as circadian rhythm disruption, smoking, alcohol, fatty acids, dietary fiber, obesity, and ultraviolet light, are known to be associated with the risk of cutaneous malignancies, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma. Although the influence of some daily lifestyles on the risk of skin cancers is controversial, this review provides us a better understanding of the relationship between daily lifestyle factors and skin cancers.
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Cutaneous Photoprotection: A Review of the Current Status and Evolving Strategies.
Suozzi, K, Turban, J, Girardi, M
The Yale journal of biology and medicine. 2020;(1):55-67
Abstract
Ultraviolet radiation (UVR) exposure is well established as the major environmental risk factor for the development of melanoma, cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). Additional risk factors including genetic mutations, other environmental agents, and immune status are important in modulating the effects of UVR. Dermatologists advocate a multi-pronged approach to minimizing UVR exposure including lifestyle modifications, UVR protective clothing, and topically applied sun-protective products, i.e. sunscreen. New Federal Drug Administration (FDA) regulations on sunscreen have brought certain long-standing ingredients in sunscreen products under scrutiny. The FDA's proposed rule for over the counter (OTC) monograph states that the inorganic sunscreens, zinc oxide and titanium dioxide, were found to be "generally recognized as safe and effective," but cite insufficient evidence to grant organic sunscreens the same designation. This proposed rule by the FDA and our increasing understanding of multifactorial mechanisms of UVR damage are an impetus for innovation and advances in sun protective technology. A complete set of strategies designed to limit the risk of UV-induced skin cell malignant transformation and tumor development must address the fuller consideration of genetic, environmental, and immune factors that cooperatively drive cutaneous carcinogenesis. Recent advances in our understanding of the biochemical processes underpinning UVR associated cutaneous cellular damage, genotoxicity, and clonal expansion provide investigators with a spectrum of opportunities for technologic innovation in the prevention of skin cancer. Strategies to improve upon current topical sunscreen formulations have strived for broader UVR spectral coverage, more favorable aesthetics, increased adherence, and minimal penetration into the living epidermis. In addition to improved sunscreens, future topical therapies may target processes within the epidermis that contribute to carcinogenesis. These include reactive species quenching, delivery of DNA repair enzymes, and targeting of cytokines essential to the proliferation of mutant keratinocytes.
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4.
Ultraviolet A protective potential of plant extracts and phytochemicals.
Skarupova, D, Vostalova, J, Rajnochova Svobodova, A
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2020;(1):1-22
Abstract
Chronic exposure to solar radiation is related to an increased incidence of various skin disorders, including premature skin aging and melanoma and non-melanoma skin cancers. Ultraviolet (UV) photons in particular are responsible for skin damage. Solar UV photons mainly belong to UVA wavebands, however UVA radiation has been mostly ignored for a long time. At the cellular level, UVA photons mainly provoke indirect oxidative damage to biomolecules via the massive generation of unstable and highly reactive compounds. Human skin has several effective mechanisms that forestall, repair and eliminate damage caused by solar radiation. Regardless, some damage persists and can accumulate with chronic exposure. Therefore, conscious protection against solar radiation (UVB+UVA) is necessary. Besides traditional types of photoprotection such as sunscreen use, new strategies are being searched for and developed. One very popular protective strategy is the application of phytochemicals as active ingredients of photoprotection preparations instead of synthetic chemicals. Phytochemicals usually possess additional biological activities besides absorbing the energy of photons, and those properties (e.g. antioxidant, anti-inflammatory) magnify the protective potential of phytochemicals and extracts. Therefore, compounds of natural origin are in the interest of researchers as well as developers. In this review, only studies on UVA protection with well-documented experimental conditions are summarized. This article includes 17 well standardized plant extracts (Camellia sinensis (L.) Kuntze, Silybum marianum L. Gaertn., Punica granatum L., Polypodium aureum L., Vaccinium myrtillus L., Lonicera caerulea L., Thymus vulgaris L., Opuntia ficus-indica (L.) Mill., Morinda citrifolia L., Aloe vera (L.) Burm.f., Oenothera paradoxa Hudziok, Galinsoga parviflora Cav., Galinsoga quadriradiata Ruiz et Pavón, Hippophae rhamnoides L., Cola acuminata Schott & Endl., Theobroma cacao L. and Amaranthus cruentus L.) and 26 phytochemicals.
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5.
Potential of Skin Microbiome, Pro- and/or Pre-Biotics to Affect Local Cutaneous Responses to UV Exposure.
Patra, V, Gallais Sérézal, I, Wolf, P
Nutrients. 2020;(6)
Abstract
The human skin hosts innumerable microorganisms and maintains homeostasis with the local immune system despite the challenges offered by environmental factors such as ultraviolet radiation (UVR). UVR causes cutaneous alterations such as acute (i.e., sunburn) and chronic inflammation, tanning, photoaging, skin cancer, and immune modulation. Phototherapy on the other hand is widely used to treat inflammatory skin diseases such as psoriasis, atopic dermatitis, polymorphic light eruption and graft-versus-host disease (GvHD), as well as neoplastic skin diseases such as cutaneous T cell lymphoma, among others. Previous work has addressed the use of pro- and pre-biotics to protect against UVR through anti-oxidative, anti-inflammatory, anti-aging, anti-carcinogenic and/or pro-and contra-melanogenic properties. Herein, we discuss and share perspectives of the potential benefits of novel treatment strategies using microbes and pro- and pre-biotics as modulators of the skin response to UVR, and how they could act both for protection against UVR-induced skin damage and as enhancers of the UVR-driven therapeutic effects on the skin.
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6.
Protective effects of 1,25 dihydroxyvitamin D3 and its analogs on ultraviolet radiation-induced oxidative stress: a review.
Jagoda, SV, Dixon, KM
Redox report : communications in free radical research. 2020;(1):11-16
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Abstract
The active vitamin D compound, 1,25-dihydroxyvitamin D3 (1,25D) is produced in skin cells following exposure to ultraviolet radiation (UV) from the sun. However, there are many harmful effects of UV which include DNA damage caused by direct absorption of UV, as well as that caused indirectly via UV-induced reactive oxygen species (ROS). Interestingly, 1,25D and analogs have been shown to reduce both direct and indirect UV-induced DNA damage in skin cells. This was accompanied by reductions in ROS and in nitric oxide products with 1,25D following UV. Moreover, following acute UV exposure, 1,25D has been demonstrated to increase p53 levels in skin, which would presumably allow for repair of cells with damaged DNA, or apoptosis of cells with irreparably damaged DNA. Previous studies have also shown that p53 reduces intracellular ROS. Furthermore, 1,25D has been shown to induce metallothioneins, which are potent free radical scavengers. In addition to these protective effects, 1,25D has been demonstrated to inhibit stress-activated c-Jun N-terminal kinases following UV exposure, and to increase levels of the stress-induced protein heme oxygenase-1 in a model of oxidative stress. Herein, we discuss the protective effects of 1,25D and analogs in the context of UV, oxidative stress and skin cancer.
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7.
Mechanisms and prevention of UV-induced melanoma.
Sample, A, He, YY
Photodermatology, photoimmunology & photomedicine. 2018;(1):13-24
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Abstract
Melanoma is the deadliest form of skin cancer and its incidence is rising, creating a costly and significant clinical problem. Exposure to ultraviolet (UV) radiation, namely UVA (315-400 nm) and UVB (280-315 nm), is a major risk factor for melanoma development. Cumulative UV radiation exposure from sunlight or tanning beds contributes to UV-induced DNA damage, oxidative stress, and inflammation in the skin. A number of factors, including hair color, skin type, genetic background, location, and history of tanning, determine the skin's response to UV radiation. In melanocytes, dysregulation of this UV radiation response can lead to melanoma. Given the complex origins of melanoma, it is difficult to develop curative therapies and universally effective preventative strategies. Here, we describe and discuss the mechanisms of UV-induced skin damage responsible for inducing melanomagenesis, and explore options for therapeutic and preventative interventions.
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8.
Hormonal Regulation of the Repair of UV Photoproducts in Melanocytes by the Melanocortin Signaling Axis.
Jarrett, SG, D'Orazio, JA
Photochemistry and photobiology. 2017;(1):245-258
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Abstract
Melanoma is the deadliest form of skin cancer because of its propensity to spread beyond the primary site of disease and because it resists many forms of treatment. Incidence of melanoma has been increasing for decades. Although ultraviolet radiation (UV) has been identified as the most important environmental causative factor for melanoma development, UV-protective strategies have had limited efficacy in melanoma prevention. UV mutational burden correlates with melanoma development and tumor progression, underscoring the importance of UV in melanomagenesis. However, besides amount of UV exposure, melanocyte UV mutational load is influenced by the robustness of nucleotide excision repair, the genome maintenance pathway charged with removing UV photoproducts before they cause permanent mutations in the genome. In this review, we highlight the importance of the melanocortin hormonal signaling axis on regulating efficiency of nucleotide excision repair in melanocytes. By understanding the molecular mechanisms by which nucleotide excision repair can be increased, it may be possible to prevent many cases of melanoma by reducing UV mutational burden over time.
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The impact of skin colour on human photobiological responses.
Fajuyigbe, D, Young, AR
Pigment cell & melanoma research. 2016;(6):607-618
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Abstract
Terrestrial solar ultraviolet radiation (UVR) exerts both beneficial and adverse effects on human skin. Epidemiological studies show a lower incidence of skin cancer in people with pigmented skins compared to fair skins. This is attributed to photoprotection by epidermal melanin, as is the poorer vitamin D status of those with darker skins. We summarize a wide range of photobiological responses across different skin colours including DNA damage and immunosuppression. Some studies show the generally modest photoprotective properties of melanin, but others show little or no effect. DNA photodamage initiates non-melanoma skin cancer and is reduced by a factor of about 3 in pigmented skin compared with white skin. This suggests that if such a modest reduction in DNA damage can result in the significantly lower skin cancer incidence in black skin, the use of sunscreen protection might be extremely beneficial for susceptible population. Many contradictory results may be explained by protocol differences, including differences in UVR spectra and exposure protocols. We recommend that skin type comparisons be done with solar-simulated radiation and standard erythema doses or physical doses (J/m2 ) rather than those based solely on clinical endpoints such as minimal erythema dose (MED).
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Novel non-calcemic secosteroids that are produced by human epidermal keratinocytes protect against solar radiation.
Slominski, AT, Janjetovic, Z, Kim, TK, Wasilewski, P, Rosas, S, Hanna, S, Sayre, RM, Dowdy, JC, Li, W, Tuckey, RC
The Journal of steroid biochemistry and molecular biology. 2015;:52-63
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Abstract
CYP11A1 hydroxylates the side chain of vitamin D3 (D3) in a sequential fashion [D3→20S(OH)D3→20,23(OH)2D3→17,20,23(OH)3D3], in an alternative to the classical pathway of activation [D3→25(OH)D3→1,25(OH)2D3]. The products/intermediates of the pathway can be further modified by the action of CYP27B1. The CYP11A1-derived products are biologically active with functions determined by the lineage of the target cells. This pathway can operate in epidermal keratinocytes. To further define the role of these novel secosteroids we tested them for protective effects against UVB-induced damage in human epidermal keratinocytes, melanocytes and HaCaT keratinocytes, cultured in vitro. The secosteroids attenuated ROS, H2O2 and NO production by UVB-irradiated keratinocytes and melanocytes, with an efficacy similar to 1,25(OH)2D3, while 25(OH)D3 had lower efficacy. These attenuations were also seen to some extent for the 20(OH)D3 precursor, 20S-hydroxy-7-dehydrocholesterol. These effects were accompanied by upregulation of genes encoding enzymes responsible for defense against oxidative stress. Using immunofluorescent staining we observed that the secosteroids reduced the generation cyclobutane pyrimidine dimers in response to UVB and enhanced expression of p53 phosphorylated at Ser-15, but not at Ser-46. Additional evidence for protection against DNA damage in cells exposed to UVB and treated with secosteroids was provided by the Comet assay where DNA fragmentation was markedly reduced by 20(OH)D3 and 20,23(OH)2D3. In conclusion, novel secosteroids that can be produced by the action of CYP11A1 in epidermal keratinocytes have protective effects against UVB radiation. This article is part of a special issue entitled '17th Vitamin D Workshop'.