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Wong ZY, Ou KQ, Wong ZN, Faderani R, Kanapathy M, Mosahebi A. Temporal trends and unbalanced distribution, in pediatric cutaneous melanoma in 204 countries and territories, 1990-2019. Pediatr Hematol Oncol 2025; 42:147-157. [PMID: 39989269 DOI: 10.1080/08880018.2025.2466023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 02/03/2025] [Accepted: 02/06/2025] [Indexed: 02/25/2025]
Abstract
Cutaneous melanoma (CM) is a rare occurrence in the pediatric population and suffers from a dearth of epidemiological data. This study aims to estimate the distribution and temporal trends of pediatric CM. Data specific to the pediatric (<20 years old) CM were extracted from the Global Burden of Disease (GBD) Study 2019, stratified by Socio-demographic Index (SDI) and WHO region. The data encompassed incidence, mortality, and disability-adjusted life-years (DALYs) representing the years of healthy life lost due to a pediatric CM diagnosis. Join point regression analysis and Quality of care index (QCI) were computed. In 2019, the global age-standardized incidence, mortality, and DALYs rates of pediatric CM were estimated at 0.13, 0.02, and 1.46 per 100,000 population, respectively. From 1990 to 2010, an increase in incidence was noted (0.95, 95% UI: 0.89 to 1.02), while mortality (-0.62, 95% UI: -0.71 to -0.53) and DALYs (-0.58, 95% UI: -0.67 to -0.50) exhibited a decline. The global QCI for pediatric melanoma in 2019 was 87, while Somalia was noted to have the lowest QCI (16). The incidence rate was predominantly observed in European regions and high SDI regions, whereas the disease burden was more pronounced in low SDI region and Africa regions. An age-related discrepancy was noted with pediatric CM being higher and more broadly distributed among western countries in children above the age of ten. This study highlights that pediatric CM remains rare but has a disproportionate global distribution, warranting targeted strategies to tackle this issue.
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Affiliation(s)
| | - Kai Qi Ou
- Queens Medical Centre, Nottingham, UK
| | | | - Ryan Faderani
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Muholan Kanapathy
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Afshin Mosahebi
- Division of Surgery and Interventional Science, University College London, London, UK
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Liu C, Liu X, Cao P, Li X, Xin H, Zhu S. Global, regional, national prevalence, mortality, and disability-adjusted life-years of cutaneous squamous cell carcinoma and trend analysis from 1990 to 2021 and prediction to 2045. Front Oncol 2025; 15:1523169. [PMID: 39980558 PMCID: PMC11839636 DOI: 10.3389/fonc.2025.1523169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 01/20/2025] [Indexed: 02/22/2025] Open
Abstract
Background A serious worldwide health concern is cutaneous squamous cell carcinoma (cSCC). For the purpose of creating focused strategies, it is essential to comprehend geographical variations in cSCC prevalence and trends. Methods This study utilized data from the 2021 Global Burden of Diseases (GBD) survey to analyze cSCC across 204 countries and territories. We assessed the age-standardized prevalence rate (ASPR), mortality rate (ASMR), disability-adjusted life years (ASDR), and estimated annual percentage changes (EAPCs), with trends stratified by region, country, age, sex, and Sociodemographic Index (SDI). To evaluate disparities in cSCC burden, we combined the SDI with the inequality slope and concentration indices for an international health inequality analysis. Decomposition analysis assessed the effects of population growth, aging, and epidemiological trends on disease burden, while frontier analysis linked cSCC outcomes with socio-demographic development. A Bayesian Age-Period-Cohort (BAPC) model projected future prevalence, mortality, and DALYs, identifying key drivers of cSCC burden. Results In 2021, there were 2,275,834 cases of cSCC globally, reflecting a 345% increase since 1990. During this period, the ASPR rose from 14.69 to 26.85 per 100,000, while the ASMR increased slightly from 0.67 to 0.69 per 100,000. Disability-adjusted life years (DALYs) rose from 544,973 to 1,210,874. Among socio-demographic regions, the high SDI region had the highest ASPR, while the middle SDI region exhibited the highest ASMR and ASDR. Decomposition analysis identified population growth and demographic aging as key drivers of the rising ASMR. Countries like Georgia showed significant disparities in frontier analysis, indicating potential for better cSCC management. Health inequality analysis confirmed that the burden was concentrated in nations with higher SDI. By 2045, the global ASPR is projected to reach 64.66, with the ASMR and ASDR expected to decrease to 1.02 and 20.63 per 100,000, respectively. Conclusion Over the last three decades, the global burden of cSCC has increased significantly. While mortality rates and DALYs are expected to decline over the next twenty years, the prevalence of cSCC is projected to remain high. This highlights the urgent need to reevaluate preventive efforts aimed at reducing morbidity, particularly in areas with substantial populations over the age of 95.
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Affiliation(s)
- Chengling Liu
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army (PLA), Guilin, China
| | - Xingchen Liu
- Department of Pathology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Pengjuan Cao
- Department of Endocrinology and Traditional Chinese Medicine, The 924th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army (PLA), Guilin, China
| | - Xin Li
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army (PLA), Guilin, China
| | - Haiming Xin
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army (PLA), Guilin, China
| | - Sailin Zhu
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army (PLA), Guilin, China
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Kaya VO, Adebali O. UV-induced reorganization of 3D genome mediates DNA damage response. Nat Commun 2025; 16:1376. [PMID: 39910043 PMCID: PMC11799157 DOI: 10.1038/s41467-024-55724-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 12/20/2024] [Indexed: 02/07/2025] Open
Abstract
While it is well-established that UV radiation threatens genomic integrity, the precise mechanisms by which cells orchestrate DNA damage response and repair within the context of 3D genome architecture remain unclear. Here, we address this gap by investigating the UV-induced reorganization of the 3D genome and its critical role in mediating damage response. Employing temporal maps of contact matrices and transcriptional profiles, we illustrate the immediate and holistic changes in genome architecture post-irradiation, emphasizing the significance of this reconfiguration for effective DNA repair processes. We demonstrate that UV radiation triggers a comprehensive restructuring of the 3D genome organization at all levels, including loops, topologically associating domains and compartments. Through the analysis of DNA damage and excision repair maps, we uncover a correlation between genome folding, gene regulation, damage formation probability, and repair efficacy. We show that adaptive reorganization of the 3D genome is a key mediator of the damage response, providing new insights into the complex interplay of genomic structure and cellular defense mechanisms against UV-induced damage, thereby advancing our understanding of cellular resilience.
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Affiliation(s)
- Veysel Oğulcan Kaya
- Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, Türkiye
| | - Ogün Adebali
- Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, Türkiye.
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Uçar N, Holick MF. Illuminating the Connection: Cutaneous Vitamin D 3 Synthesis and Its Role in Skin Cancer Prevention. Nutrients 2025; 17:386. [PMID: 39940244 PMCID: PMC11821240 DOI: 10.3390/nu17030386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/16/2025] [Accepted: 01/20/2025] [Indexed: 02/14/2025] Open
Abstract
Sunlight exposure plays an important role in human health, impacting processes such as mood, blood pressure regulation, and vitamin D3 production. Solar ultraviolet B radiation initiates vitamin D3 synthesis in the skin, which is subsequently metabolized into its biologically active form. UVB exposure plays a key role in enabling vitamin D3 synthesis, but it can also contribute to skin carcinogenesis, creating a complex interplay between its beneficial and harmful effects. Vitamin D deficiency, affecting over half the global population, is linked to a range of chronic diseases, including cancers, cardiovascular conditions, and autoimmune disorders. Simultaneously, excessive solar UVB exposure increases the risk of non-melanoma and melanoma skin cancers through mechanisms involving DNA damage and oxidative stress. This review examines the dual role of UVB radiation in health and disease, focusing on the mechanisms of cutaneous vitamin D3 synthesis, the epidemiology of skin cancer, and the protective roles of vitamin D3's photoproducts and its active metabolite, 1,25-dihydroxyvitamin D3. Understanding these interconnections is critical for developing strategies that balance adequate sun-induced vitamin D3 production with skin cancer prevention.
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Affiliation(s)
- Nazlı Uçar
- Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA;
- Area of Preventive Medicine and Public Health, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology, and Legal Medicine, School of Pharmacy, University de Valencia, 46100 Burjassot, Spain
| | - Michael F. Holick
- Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA;
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Lee MK, Jeong HH, Kim MJ, Seo JS, Hwang JY, Jung WK, Moon KM, Lee I, Lee B. The Beneficial Roles of Sargassum spp. in Skin Disorders. J Med Food 2024; 27:359-368. [PMID: 38526569 DOI: 10.1089/jmf.2023.k.0160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2024] Open
Abstract
As the body's largest organ, the skin is located at the internal and external environment interface, serving as a line of defense against various harmful stressors. Recently, marine-derived physiologically active ingredients have attracted considerable attention in the cosmeceutical industry due to their beneficial effects on skin health. Sargassum, a genus of brown macroalgae, has traditionally been consumed as food and medicine in several countries and is rich in bioactive compounds such as meroterpenoids, sulfated polysaccharides, fucoidan, fucoxanthin, flavonoids, and terpenoids. Sargassum spp. have various beneficial effects on skin disorders. They help with atopic dermatitis by improving skin barrier protection and reducing inflammation. Several species show potential in treating acne by inhibiting bacterial growth and reducing inflammation. Some species, such as Sargassum horneri, demonstrate antiallergic effects by modulating mast cell activity. Certain Sargassum species exhibit anticancer activity by inhibiting tumor growth and promoting apoptosis, and some species help with wound healing by promoting angiogenesis and reducing oxidative stress. Overall, Sargassum spp. demonstrate potential for treating and managing various skin conditions. Therefore, the bioactive compounds of Sargassum spp. may be natural ingredients with a wide range of functional properties for preventing and treating skin disorders. The present review focused on the various biological effects of Sargassum extracts and derived compounds on skin disorders.
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Affiliation(s)
- Min-Kyeong Lee
- Department of Food Science and Nutrition, Pukyong National University, Busan, Korea
- Biotechnology Research Division, National Institute of Fisheries Science, Busan, Republic of Korea
| | - Hyeon Hak Jeong
- Department of Smart Green Technology Engineering, Pukyong National University, Busan, Korea
| | - Myeong-Jin Kim
- Department of Food Science and Nutrition, Pukyong National University, Busan, Korea
| | - Jae Seong Seo
- Department of Smart Green Technology Engineering, Pukyong National University, Busan, Korea
| | - Ji Young Hwang
- Department of Smart Green Technology Engineering, Pukyong National University, Busan, Korea
| | - Won-Kyo Jung
- Division of Biomedical Engineering and Research Center for Marine Integrated Bionics Technology, Pukyong National University, Busan, Korea
| | - Kyoung Mi Moon
- Department of Food Science and Nutrition, Pukyong National University, Busan, Korea
| | - Incheol Lee
- Department of Ocean Engineering, Pukyong National University, Busan, Korea
| | - Bonggi Lee
- Department of Food Science and Nutrition, Pukyong National University, Busan, Korea
- Department of Smart Green Technology Engineering, Pukyong National University, Busan, Korea
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Letsoalo K, Nortje E, Patrick S, Nyakudya T, Hlophe Y. Decoding the synergistic potential of MAZ-51 and zingerone as therapy for melanoma treatment in alignment with sustainable development goals. Cell Biochem Funct 2024; 42:e3950. [PMID: 38348768 DOI: 10.1002/cbf.3950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 12/28/2023] [Accepted: 01/29/2024] [Indexed: 02/15/2024]
Abstract
Melanoma, an invasive class of skin cancer, originates from mutations in melanocytes, the pigment-producing cells. Globally, approximately 132,000 new cases are reported each year, and in South Africa, the incidence stands at 2.7 per 100,000 people, signifying a worrisome surge in melanoma rates. Therefore, there is a need to explore treatment modalities that will target melanoma's signalling pathways. Melanoma metastasis is aided by ligand activity of transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor-C (VEGF-C) and C-X-C chemokine ligand 12 (CXCL12) which bind to their receptors and promote tumour cell survival, lymphangiogenesis and chemotaxis. (3-(4-dimethylaminonaphthelen-1-ylmethylene)-1,3-dihydroindol-2-one) MAZ-51 is an indolinone-based molecule that inhibits VEGF-C induced phosphorylation of vascular endothelial growth factor receptor 3 (VEGFR-3). Despite the successful use of conventional cancer therapies, patients endure adverse side effects and cancer drug resistance. Moreover, conventional therapies are toxic to the environment and caregivers. The use of medicinal plants and their phytochemical constituents in cancer treatment strategies has become more widespread because of the rise in drug resistance and the development of unfavourable side effects. Zingerone, a phytochemical derived from ginger exhibits various pharmacological properties positioning it as a promising candidate for cancer treatment. This review provides an overview of melanoma biology and the intracellular signalling pathways promoting cell survival, proliferation and adhesion. There is a need to align health and environmental objectives within sustainable development goals 3 (good health and well-being), 13 (climate action) and 15 (life on land) to promote early detection of skin cancer, enhance sun-safe practices, mitigation of environmental factors and advancing the preservation of biodiversity, including medicinal plants. Thus, this review discusses the impact of cytostatic cancer drugs on patients and the environment and examines the potential use of phytochemicals as adjuvant therapy.
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Affiliation(s)
- Kganya Letsoalo
- Department of Physiology, University of Pretoria, Pretoria, South Africa
| | - Evangeline Nortje
- Department of Physiology, University of Pretoria, Pretoria, South Africa
| | - Sean Patrick
- Environmental Chemical Pollution and Health Research Unit, University of Pretoria, Pretoria, South Africa
| | - Trevor Nyakudya
- Department of Physiology, University of Pretoria, Pretoria, South Africa
| | - Yvette Hlophe
- Department of Physiology, University of Pretoria, Pretoria, South Africa
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Vallini G, Calabrese L, Canino C, Trovato E, Gentileschi S, Rubegni P, Tognetti L. Signaling Pathways and Therapeutic Strategies in Advanced Basal Cell Carcinoma. Cells 2023; 12:2534. [PMID: 37947611 PMCID: PMC10647618 DOI: 10.3390/cells12212534] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 10/24/2023] [Accepted: 10/25/2023] [Indexed: 11/12/2023] Open
Abstract
Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide. In detail, basal cell carcinoma (BCC) is the most frequent malignancy in the fair-skinned population. The incidence of BCC remains difficult to assess due to the poor registration practice; however, it has been increasing in the last few years. Approximately, 85% of sporadic BCCs carry mutations in Hedgehog pathway genes, especially in PTCH, SUFU and SMO genes, which lead to the aberrant activation of GLI transcriptional factors, typically silent in cells of adult individuals. The management of advanced BCC (aBCC), both metastatic (mBCC) and locally advanced BCC (laBCC), not candidates for surgical excision or radiotherapy, remains challenging. The discovery of mutations in the Hh signaling pathway has paved the way for the development of Hh pathway inhibiting agents, such as vismodegib and sonidegib, which have represented a breakthrough in the aBCC management. However, the use of these agents is limited by the frequent occurrence of adverse events or the development of drug resistance. In this review, we thoroughly describe the current knowledge regarding the available options for the pharmacological management of aBCCs and provide a forward-looking update on novel therapeutic strategies that could enrich the therapeutic armamentarium of BCC in the near future.
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Affiliation(s)
- Giulia Vallini
- Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Laura Calabrese
- Department of Medical, Surgical and Neurological Sciences, Division of Dermatology, University of Siena, 53100 Siena, Italy; (L.C.); (E.T.); (P.R.); (L.T.)
- Institute of Dermatology, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Costanza Canino
- Department of Haematology, Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, 00165 Rome, Italy;
| | - Emanuele Trovato
- Department of Medical, Surgical and Neurological Sciences, Division of Dermatology, University of Siena, 53100 Siena, Italy; (L.C.); (E.T.); (P.R.); (L.T.)
| | - Stefano Gentileschi
- Department of Medical, Surgical and Neurological Sciences, Division of Rheumatology, University of Siena, 53100 Siena, Italy;
| | - Pietro Rubegni
- Department of Medical, Surgical and Neurological Sciences, Division of Dermatology, University of Siena, 53100 Siena, Italy; (L.C.); (E.T.); (P.R.); (L.T.)
| | - Linda Tognetti
- Department of Medical, Surgical and Neurological Sciences, Division of Dermatology, University of Siena, 53100 Siena, Italy; (L.C.); (E.T.); (P.R.); (L.T.)
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8
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Fernandes A, Rodrigues PM, Pintado M, Tavaria FK. A systematic review of natural products for skin applications: Targeting inflammation, wound healing, and photo-aging. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 115:154824. [PMID: 37119762 DOI: 10.1016/j.phymed.2023.154824] [Citation(s) in RCA: 67] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 04/04/2023] [Accepted: 04/15/2023] [Indexed: 05/21/2023]
Abstract
BACKGROUND Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between antioxidant defenses and reactive oxygen species, the skin no longer can keep its integrity and homeostasis. Chronic inflammation, premature skin aging, tissue damage, and immunosuppression are possible consequences induced by sustained exposure to environmental and endogenous reactive oxygen species. Skin immune and non-immune cells together with the microbiome are essential to efficiently trigger skin immune responses to stress. For this reason, an ever-increasing demand for novel molecules capable of modulating immune functions in the skin has risen the level of their development, particularly in the field of natural product-derived molecules. PURPOSE In this review, we explore different classes of molecules that showed evidence in modulate skin immune responses, as well as their target receptors and signaling pathways. Moreover, we describe the role of polyphenols, polysaccharides, fatty acids, peptides, and probiotics as possible treatments for skin conditions, including wound healing, infection, inflammation, allergies, and premature skin aging. METHODS Literature was searched, analyzed, and collected using databases, including PubMed, Science Direct, and Google Scholar. The search terms used included "Skin", "wound healing", "natural products", "skin microbiome", "immunomodulation", "anti-inflammatory", "antioxidant", "infection", "UV radiation", "polyphenols", "polysaccharides", "fatty acids", "plant oils", "peptides", "antimicrobial peptides", "probiotics", "atopic dermatitis", "psoriasis", "auto-immunity", "dry skin", "aging", etc., and several combinations of these keywords. RESULTS Natural products offer different solutions as possible treatments for several skin conditions. Significant antioxidant and anti-inflammatory activities were reported, followed by the ability to modulate immune functions in the skin. Several membrane-bound immune receptors in the skin recognize diverse types of natural-derived molecules, promoting different immune responses that can improve skin conditions. CONCLUSION Despite the increasing progress in drug discovery, several limiting factors need future clarification. Understanding the safety, biological activities, and precise mechanisms of action is a priority as well as the characterization of the active compounds responsible for that. This review provides directions for future studies in the development of new molecules with important pharmaceutical and cosmeceutical value.
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Affiliation(s)
- A Fernandes
- Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal.
| | - P M Rodrigues
- Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
| | - M Pintado
- Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
| | - F K Tavaria
- Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
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Fernandez-Flores A. [Translated article] Modern Concepts in Melanocytic Tumors. ACTAS DERMO-SIFILIOGRAFICAS 2023; 114:T402-T412. [PMID: 37068631 DOI: 10.1016/j.ad.2023.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 01/03/2023] [Indexed: 04/19/2023] Open
Abstract
The advent of molecular pathology has fueled unprecedented advances in the diagnosis and understanding of melanocytic tumors. These advances, however, have also generated concepts that may be difficult to grasp for clinical practitioners, who are not always conversant with the array of genetic techniques employed in the laboratory. These same practitioners, however, are being increasingly called on to provide treatments that are often based on the latest molecular findings for melanocytic tumors. We review the most recent concepts in the pathway classification of melanocytic tumors, including intermediate lesions known as melanocytomas. We examine the genetic and molecular techniques used to study these tumors, look at where they overlap, and discuss their limitations and some of the most difficult-to-interpret results.
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Affiliation(s)
- A Fernandez-Flores
- Servicio de Anatomía Patológica, Hospital Universitario El Bierzo, Ponferrada, León, Spain; Servicio de Anatomía Patológica, Hospital de la Reina, Ponferrada, León, Spain; Departamento de Investigación, Instituto de Investigaciones Biomédicas A Coruña (INIBIC), Universidad de A Coruña (UDC), A Coruña, Spain.
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10
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Bonamy C, Pesnel S, Ben Haddada M, Gorgette O, Schmitt C, Morel AL, Sauvonnet N. Impact of Green Gold Nanoparticle Coating on Internalization, Trafficking, and Efficiency for Photothermal Therapy of Skin Cancer. ACS OMEGA 2023; 8:4092-4105. [PMID: 36743010 PMCID: PMC9893490 DOI: 10.1021/acsomega.2c07054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 12/29/2022] [Indexed: 06/18/2023]
Abstract
Skin cancer is a global health issue and mainly composed of melanoma and nonmelanoma cancers. For the first clinical proof of concept on humans, we decided to study good prognosis skin cancers, i.e., carcinoma basal cell. In UE, the first-line treatment remains surgical resection, healing most of the tumors, but presents aesthetic disadvantages with a high reoccurrence rate on exposed areas. Moreover, the therapeutic indications could extend to melanoma and metastasis, which is a different medical strategy that could combine this treatment. Indeed, patients with late-stage melanoma are in a therapeutic impasse, despite recent targeted and immunological therapies. Photothermal therapy using gold nanoparticles is the subject of many investigations due to their strong potential to treat cancers by physical, thermal destruction. We developed gold nanoparticles synthesized by green chemistry (gGNPs), using endemic plant extract from Reunion Island, which have previously showed their efficiency at a preclinical stage. Here, we demonstrate that these gGNPs are less cytotoxic than gold nanoparticles synthesized by Turkevich's method. Furthermore, our work describes the optimization of gGNP coating and stabilization, also taking into consideration the gGNP path in cells (endocytosis, intracellular trafficking, and exocytosis), their specificity toward cancerous cells, their cytotoxicity, and their in vivo efficiency. Finally, based on the metabolic switch of cancerous cells overexpressing Glut transporters in skin cancers, we demonstrated that glucose-stabilized gGNP (gGNP@G) enables a quick internalization, fourfold higher in cancerous cells in contrast to healthy cells with no side cytotoxicity, which is particularly relevant to target and treat cancer.
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Affiliation(s)
- Clément Bonamy
- Torskal, 2 rue Maxime Rivière, 97490 Sainte-Clotilde, France
- Group
Intracellular Trafficking and Tissue Homeostasis, Institut Pasteur, Université Paris Cité, 75015 Paris, France
| | - Sabrina Pesnel
- Torskal, 2 rue Maxime Rivière, 97490 Sainte-Clotilde, France
| | | | - Olivier Gorgette
- Ultrastructural
BioImaging, Institut Pasteur, Université
Paris Cité, 75015 Paris, France
| | - Christine Schmitt
- Ultrastructural
BioImaging, Institut Pasteur, Université
Paris Cité, 75015 Paris, France
| | | | - Nathalie Sauvonnet
- Group
Intracellular Trafficking and Tissue Homeostasis, Institut Pasteur, Université Paris Cité, 75015 Paris, France
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Modern Concepts in Melanocytic Tumors. ACTAS DERMO-SIFILIOGRAFICAS 2023; 114:402-412. [PMID: 36649787 DOI: 10.1016/j.ad.2023.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 11/29/2022] [Accepted: 01/03/2023] [Indexed: 01/15/2023] Open
Abstract
The advent of molecular pathology has fueled unprecedented advances in the diagnosis and understanding of melanocytic tumors. These advances, however, have also generated concepts that may be difficult to grasp for clinical practitioners, who are not always conversant with the array of genetic techniques employed in the laboratory. These same practitioners, however, are being increasingly called on to provide treatments that are often based on the latest molecular findings for melanocytic tumors. We review the most recent concepts in the pathway classification of melanocytic tumors, including intermediate lesions known as melanocytomas. We examine the genetic and molecular techniques used to study these tumors, look at where they overlap, and discuss their limitations and some of the most difficult-to-interpret results.
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12
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Kuryk L, Møller ASW. Next generation oncolytic viruses expressing PADI1 and TIMP2 exhibit anti-tumor activity against melanoma in nude and humanized mouse models. Mol Ther Oncolytics 2023; 28:158-170. [PMID: 36816748 PMCID: PMC9922816 DOI: 10.1016/j.omto.2023.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open
Abstract
Immunotherapy of metastatic melanoma (MM) has vastly improved the longevity of only a minority of patients. To broaden the repertoire of agents against MM, we investigated the effectiveness of locally interrupting tumor blood endothelial cell proliferation and angiogenesis, arginine deprivation, or both on the growth of melanoma by constructing and characterizing the effectiveness of four oncolytic adenoviruses. ONCOS-207 (which expressed tissue inhibitor of metalloprotease type 2 [TIMP2]), ONCOS-209 (which expressed peptidyl arginine deiminase [PADI1]), and ONCOS-210 and ONCOS-212 (which expressed both TIMP2 and PADI1) exhibited oncolytic activity against four melanoma cell lines in vitro. ONCOS-212 treatments significantly inhibited tumor growth in an A2058 tumor model in nude mice compared with vehicle control. The inhibitory effects of the two transgenes of ONCOS-212 on tumor growth appeared to be synergistic. These viruses also significantly inhibited tumor growth in a humanized NOG model of melanoma (A2058 xenograft). All viruses significantly increased the percentage of activated CD8+ T cells in the tumor-infiltrating lymphocytes. The abscopal effect of ONCOS-212 treatments in the A2058 tumor challenge model in hNOG mice supports the hypothesis that the human immune response contributes to the anti-tumor activity of ONCOS-212. These results support the further development of ONCOS-212 for cancer treatment.
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Affiliation(s)
- Lukasz Kuryk
- Targovax ASA, Clinical Science, Vollsveien 19, NO-1366 Lysaker Oslo, Norway,National Institute of Public Health NIH – National Research Institute, Department of Virology, Chocimska 24, 00-791 Warsaw, Poland,Corresponding author: Lukasz Kuryk, National Institute of Public Health NIH – National Research Institute, Department of Virology, Chocimska 24, 00-791 Warsaw, Poland.
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Han J, Jang Y, Shin DY, Lee J, Seo YR. A Genomic Approach to Identify the Different between Acute and Chronic UVB Exposures in the Causation of Inflammation and Cancer. J Cancer Prev 2022; 27:199-207. [PMID: 36713944 PMCID: PMC9836911 DOI: 10.15430/jcp.2022.27.4.199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 12/29/2022] [Indexed: 01/11/2023] Open
Abstract
As a principal component of solar radiation, ultraviolet B (UVB) exposure can be harmful depending on the duration and intensity because the human body can easily be exposed to it. Many studies have demonstrated that UVB causes a series of inflammatory and other skin disorders. UVB has been classified as the Group 1 carcinogen by the International Agency for Research on Cancer. Diverse studies have focused on UVB exposure but the complex perspective of acute and chronic UVB exposure is still lacking. This review presents the differences between acute and chronic exposure to UVB and summarizes public information in terms of toxicogenomic characteristics. We also demonstrated the differences between adverse effects of acute and chronic UVB exposure on the skin system. From the published literatures, we compared the biological pathways predict of the adverse effects caused by each UVB exposure type. Furthermore, our review not only clarifies the differences in each UVB exposure network but also suggests major hub genes related to cellular mechanisms and diseases that are thought to be affected by acute and chronic UVB exposure.
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Affiliation(s)
- JunPyo Han
- Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University Biomedi Campus, Goyang, Korea
| | - Yujin Jang
- Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University Biomedi Campus, Goyang, Korea
| | - Dong Yeop Shin
- Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University Biomedi Campus, Goyang, Korea
| | - Jun Lee
- Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University Biomedi Campus, Goyang, Korea
| | - Young Rok Seo
- Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University Biomedi Campus, Goyang, Korea,Correspondence to Young Rok Seo, E-mail: , https://orcid.org/0000-0002-4093-4073
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Evaluation of the skin protective effects of niosomal-entrapped annona squamosa against UVA irradiation. PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES : OFFICIAL JOURNAL OF THE EUROPEAN PHOTOCHEMISTRY ASSOCIATION AND THE EUROPEAN SOCIETY FOR PHOTOBIOLOGY 2022; 21:2231-2241. [PMID: 36030490 DOI: 10.1007/s43630-022-00291-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 08/16/2022] [Indexed: 12/24/2022]
Abstract
Annona squamosa is a medicinal plant that has been used in folk medicine since antiquity. The goal of this study is to see how effective Annona squamosa leaf extract (A.S.L.E) or its niosomal-entrapped preparation is at protecting skin from UVA irradiation. The prepared niosomal-entrapped A.S.L.E has been characterized via spectrophotometry and transmission electron microscopy imaging. Furthermore, the entrapment efficiency and in vitro release of A.S.L.E were determined. In this study, ex vivo and freshly prepared samples from the dorsal region of the rats' skin were used as biological samples, which were divided into five groups: control UVA-unexposed, unprotected UVA-exposed, A.S.L.E-protected UVA-exposed, and niosomal-entrapped A.S.L.E UVA-exposed. UVA irradiation was performed by exposing the skin samples to a UVA-producing lamp for 4 h. Samples from various groups were then examined using FTIR spectroscopy, histopathology, and protein electrophoresis methods. The results showed that A.S.L.E has a skin protective effect against UVA irradiation. The niosomal-entrapped A.S.L.E was more effective than the native plant leaf extract in protecting skin from the damaging effects of UVA. Therefore, the nanotechnologically formulated preparation, niosomal-entrapped A.S.L.E, can be used as an effective photoprotector (sunscreen) against the adverse effects of UVA radiation.
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Laminin Immunostaining in Biopsies as a Useful Biomarker of Early Invasion in Actinic Cheilitis and Differential Diagnosis Between Actinic Cheilitis and Lip Cancer: New Insights. Head Neck Pathol 2022:10.1007/s12105-022-01504-y. [PMID: 36303015 DOI: 10.1007/s12105-022-01504-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 09/25/2022] [Indexed: 02/09/2023]
Abstract
BACKGROUND Squamous cell carcinoma of the lip (LSCC) and oral cavity can be life-threatening if not diagnosed early. Precancerous lesions like actinic cheilitis (AC), can transform into LSCC. Laminin is a fundamental component for basement membrane (BM) and its integrity may prevent neoplastic invasion. Therefore, laminin immunostaining of BM may be useful in identifying early invasion in actinic cheilitis and thus in the differential diagnosis between AC and invasive LSCC or high-grade epithelial dysplasia (ED). MATERIALS AND METHODS Biopsies from 46 patients with oral lesions were histologically analyzed and immunohistochemically stained for laminin-1. RESULTS AC was diagnosed in 34 patients and LSCC in 12 patients, including 3 patients with AC and concomitant high-grade ED/in situ carcinoma. Laminin-1 immunostaining revealed intense and linear expression of the BM in AC with low-grade ED. Loss of laminin expression was observed in LSCC. Intracellular laminin expression in parabasal cells was noted in AC with high-grade ED/in situ carcinoma. CONCLUSION Laminin immunostaining could be useful in identifying AC cases suspected of early invasion. It could also contribute to the histopathological differential diagnosis between AC with low- and high-grade ED and between AC and invasive LSCC. The findings of this study provide new insights into the mechanism involved in the progression process of AC into LSCC, encouraging preclinical studies that may document the stochastic role of laminin in this process.
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Bruns L, Panagiota V, von Hardenberg S, Schmidt G, Adriawan IR, Sogka E, Hirsch S, Ahrenstorf G, Witte T, Schmidt RE, Atschekzei F, Sogkas G. Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors. Front Immunol 2022; 13:742530. [PMID: 35250968 PMCID: PMC8893227 DOI: 10.3389/fimmu.2022.742530] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 01/19/2022] [Indexed: 12/02/2022] Open
Abstract
Objective The aim of this study was to investigate the prevalence of cancer and associating clinical, immunological, and genetic factors in a German cohort of patients with common variable immunodeficiency (CVID). Methods In this retrospective monocenter cohort study, we estimated the standardized incidence ratio (SIR) for different forms of cancer diagnosed in CVID patients. Furthermore, we evaluated the likely association of infectious and non-infectious CVID-related phenotypes with the diagnosis of cancer by calculation of the odds ratio. The genetic background of CVID in patients with cancer was evaluated with sequential targeted next-generation sequencing (tNGS) and whole-exome sequencing (WES). Patients’ family history and WES data were evaluated for genetic predisposition to cancer. Results A total of 27/219 patients (12.3%) were diagnosed with at least one type of cancer. Most common types of cancer were gastric cancer (SIR: 16.5), non-melanoma skin cancer (NMSC) (SIR: 12.7), and non-Hodgkin lymphoma (NHL) (SIR: 12.2). Immune dysregulation manifesting as arthritis, atrophic gastritis, or interstitial lung disease (ILD) was associated with the diagnosis of cancer. Furthermore, diagnosis of NMSC associated with the diagnosis of an alternative type of cancer. Studied immunological parameters did not display any significant difference between patients with cancer and those without. tNGS and/or WES yielded a definite or likely genetic diagnosis in 11.1% of CVID patients with cancer. Based on identified variants in cancer-associated genes, the types of diagnosed cancers, and family history data, 14.3% of studied patients may have a likely genetic susceptibility to cancer, falling under a known hereditary cancer syndrome. Conclusions Gastric cancer, NMSC, and NHL are the most frequent CVID-associated types of cancer. Manifestations of immune dysregulation, such as arthritis and ILD, were identified as risk factors of malignancy in CVID, whereas studied immunological parameters or the identification of a monogenic form of CVID appears to have a limited role in the evaluation of cancer risk in CVID.
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Affiliation(s)
- Luzia Bruns
- Department of Rheumatology and Immunology, Hannover Medical School, Hanover, Germany
| | - Victoria Panagiota
- Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
| | | | - Gunnar Schmidt
- Department of Human Genetics, Hannover Medical School, Hanover, Germany
| | | | - Eleni Sogka
- Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stefanie Hirsch
- Department of Rheumatology and Immunology, Hannover Medical School, Hanover, Germany
| | - Gerrit Ahrenstorf
- Department of Rheumatology and Immunology, Hannover Medical School, Hanover, Germany
| | - Torsten Witte
- Department of Rheumatology and Immunology, Hannover Medical School, Hanover, Germany
- Hannover Medical School, Cluster of Excellence RESIST (EXC 2155), Hanover, Germany
| | - Reinhold Ernst Schmidt
- Department of Rheumatology and Immunology, Hannover Medical School, Hanover, Germany
- Hannover Medical School, Cluster of Excellence RESIST (EXC 2155), Hanover, Germany
| | - Faranaz Atschekzei
- Department of Rheumatology and Immunology, Hannover Medical School, Hanover, Germany
- Hannover Medical School, Cluster of Excellence RESIST (EXC 2155), Hanover, Germany
| | - Georgios Sogkas
- Department of Rheumatology and Immunology, Hannover Medical School, Hanover, Germany
- Hannover Medical School, Cluster of Excellence RESIST (EXC 2155), Hanover, Germany
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Kim KW, Kwon YM, Kim SY, Kim JYH. One-pot synthesis of UV-protective carbon nanodots from sea cauliflower (Leathesia difformis). ELECTRON J BIOTECHN 2022. [DOI: 10.1016/j.ejbt.2021.12.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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18
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Hezaveh E, Jafari S, Jalilpiran Y, Zargarzadeh N, Mahdavi R, Gargari BP. Dietary components and the risk of non-melanoma skin cancer: A systematic review of epidemiological studies. Crit Rev Food Sci Nutr 2021:1-16. [PMID: 34933633 DOI: 10.1080/10408398.2021.2016600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Non-melanoma skin cancer (NMSC) is the most common cancer among white-skinned people. The main environmental risk factor for all types of skin cancer is ultraviolet (UV) exposure to the sun. However, significant modifiable risk factors, such as diet, have been studied about NMSC risk. Several original studies have been conducted on the link between various dietary components and the risk of NMSC in the past decade, but have not been systematically reviewed. This review focuses on the potential impact of dietary components in the prevention of NMSC and evaluates the findings of epidemiologic evidence for dietary factors. We conducted a systematic search of three databases, including Scopus, ISI Web of Science, and PubMed, to identify relevant epidemiological studies published between 2000 and July 6, 2021. Finally, forty-three articles were included. Because of the inherent limitations of epidemiological studies, no definitive conclusions can be drawn; however, the links between folate, citrus, caffeine, and alcohol with BCC are notable; thus, high dietary folate intake, as well as citrus and alcohol consumption, are associated with an increased risk of basal cell carcinoma (BCC), whereas caffeine is associated with a lower risk. More research is required to reach a definitive conclusion.
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Affiliation(s)
- Erfan Hezaveh
- Department of Biochemistry and Dietetics, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sahar Jafari
- Department of Community Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yahya Jalilpiran
- Department of Clinical Nutrition, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Nikan Zargarzadeh
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Mahdavi
- Nutrition Research Center, Department of Biochemistry and Dietetics, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Bahram Pourghassem Gargari
- Nutrition Research Center, Department of Biochemistry and Dietetics, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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19
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Rollison DE, Messina JL, Cherpelis BS, Fenske NA, Schell MJ, Adeegbe DO, Zhao Y, Amorrortu RP, Akuffo AA, Hesterberg RS, Epling-Burnette PK. Circulating Immunosuppressive Regulatory T Cells Predict Risk of Incident Cutaneous Squamous Cell Carcinoma. Front Med (Lausanne) 2021; 8:735585. [PMID: 34796183 PMCID: PMC8593034 DOI: 10.3389/fmed.2021.735585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 10/04/2021] [Indexed: 11/13/2022] Open
Abstract
Ultraviolet radiation exposure (UVR) is a risk factor for cutaneous squamous cell carcinoma (cuSCC) and has been shown to be positively associated with circulating immunosuppressive regulatory T cells ("Tregs"). However, the risk of cuSCC in association with circulating Tregs has not been studied. The aim of this study was to determine whether circulating Treg levels are associated with cuSCC development, particularly in the context of high UVR. Blood and spectrophotometer-based UVR measurements were obtained on 327 immunocompetent individuals undergoing routine skin cancer screenings at baseline and followed for up to 4 years for incident cuSCC development within a prospective cohort study. Proportions of phenotypically distinct Tregs, especially CCR4hi and CLA+ cells which are associated with activation and homing, respectively, were measured by flow cytometry. Tregs in cuSCC tumors were assessed using immunohistochemistry and graded for solar elastosis, a measure of cumulative UVR damage. Of several Treg phenotypes examined, higher levels of circulating CCR4hi Tregs at baseline were significantly associated with increased risk of subsequent cuSCC; those with higher levels of both CCR4hi and UVR were four times more likely to develop cuSCC compared to those with lower levels of both (Hazard Ratio = 4.11, 95% CI = 1.22-13.90). Within cuSCC tumors, CCR4hi Tregs were positively associated with solar elastosis. Results show that a higher proportion of CCR4hi peripheral Tregs predicts incident cuSCC up to 4 years, especially among highly UV-exposed individuals. Research of the underpinning biology of Tregs in UVR-associated skin damage may possibly reveal novel opportunities for screening, prevention, and treatment.
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Affiliation(s)
- Dana E Rollison
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, United States
| | - Jane L Messina
- Departments of Pathology and Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, United States
| | - Basil S Cherpelis
- Department of Dermatology and Cutaneous Surgery, University of South Florida College of Medicine, Tampa, FL, United States
| | - Neil A Fenske
- Department of Dermatology and Cutaneous Surgery, University of South Florida College of Medicine, Tampa, FL, United States
| | - Michael J Schell
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, United States
| | - Dennis O Adeegbe
- Department of Immunology, Moffitt Cancer Center, Tampa, FL, United States
| | - Yayi Zhao
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, United States
| | | | - Afua A Akuffo
- Department of Immunology, Moffitt Cancer Center, Tampa, FL, United States
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20
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Magee BH, Forsberg ND. Testing the validity of a proposed dermal cancer slope factor for Benzo[a]pyrene. Regul Toxicol Pharmacol 2020; 120:104852. [PMID: 33359623 DOI: 10.1016/j.yrtph.2020.104852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 12/14/2020] [Accepted: 12/17/2020] [Indexed: 10/22/2022]
Abstract
In 2014, the United States Environmental Protection Agency (EPA) proposed a Dermal Slope Factor (DSF) for benzo[a]pyrene (BaP) of 0.006 (μg/day)-1 (USEPA 2014a). It would make cancer risk estimates associated with soil contact 100 times greater than those from soil ingestion and would predict that a large fraction of skin Basal Cell Carcinomas (BCCs) and Squamous Cell Carcinomas (SCCs) worldwide are caused by low level dermal exposures to PAHs, such as BaP. This is not logical given that sunlight (ultraviolet radiation (UV)) exposure is the generally recognized cause of BCCs and SCCs. This paper critically evaluates the proposed DSF. First, a reality check is performed using EPA standard risk assessment methods and comparing the results to actual BCC and SCC rates in the U.S. population. Then, the biological plausibility of the mechanism by which PAHs might cause human skin cancer is evaluated by exploring the generally recognized etiology of human skin cancer and comparing the genetic mutation signatures of rodent skin tumors caused by PAH exposures to those of human skin cancers. It is concluded that scientific flaws resulted in a proposed DSF value that greatly overestimates the skin cancer risk for humans dermally exposed to BaP in soil.
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Affiliation(s)
- Brian H Magee
- Arcadis U.S., Inc., One Executive Drive, Suite 303, Chelmsford, MA, 01824, United States.
| | - Norman D Forsberg
- Arcadis U.S., Inc, 855 Route 146, Suite 210, Clifton Park, NY, 12065, United States
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21
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Next-generation sequencing implicates oncogenic roles for p53 and JAK/STAT signaling in microcystic adnexal carcinomas. Mod Pathol 2020; 33:1092-1103. [PMID: 31857679 DOI: 10.1038/s41379-019-0424-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 10/24/2019] [Accepted: 10/31/2019] [Indexed: 12/21/2022]
Abstract
Microcystic adnexal carcinoma is a locally aggressive sweat gland carcinoma characterized by its infiltrative growth and histopathologic overlap with benign adnexal tumors, often posing challenges to both diagnosis and management. Understanding the molecular underpinnings of microcystic adnexal carcinoma may allow for more accurate diagnosis and identify potential targetable oncogenic drivers. We characterized 18 microcystic adnexal carcinomas by targeted, multiplexed PCR-based DNA next-generation sequencing of the coding sequence of over 400 cancer-relevant genes. The majority of cases had relatively few (<8) prioritized somatic mutations, and lacked an ultraviolet (UV) signature. The most recurrent mutation was TP53 inactivation in four (22%) tumors. Frame-preserving insertions affecting the kinase domain of JAK1 were detected in three (17%) cases, and were nonoverlapping with TP53 mutations. Seven (39%) cases demonstrated copy number gain of at least one oncogene. By immunohistochemistry, p53 expression was significantly higher in microcystic adnexal carcinomas with TP53 mutations compared with those without such mutations and syringomas. Similarly, phospho-STAT3 expression was significantly higher in microcystic adnexal carcinomas harboring JAK1 kinase insertions compared with those with wild-type JAK1 and syringomas. In conclusion, microcystic adnexal carcinomas are molecularly heterogeneous tumors, with inactivated p53 or activated JAK/STAT signaling in a subset. Unlike most other nonmelanoma skin cancers involving sun-exposed areas, most microcystic adnexal carcinomas lack evidence of UV damage, and hence likely originate from a relatively photo-protected progenitor population in the dermis. These findings have implications for the biology, diagnosis, and treatment of microcystic adnexal carcinomas, including potential for therapeutic targeting of p53 or the JAK/STAT pathway in advanced tumors.
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22
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Lignin as a UV Light Blocker-A Review. Polymers (Basel) 2020; 12:polym12051134. [PMID: 32429134 PMCID: PMC7284897 DOI: 10.3390/polym12051134] [Citation(s) in RCA: 119] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 04/29/2020] [Accepted: 05/08/2020] [Indexed: 01/08/2023] Open
Abstract
Lignin is the by-product of pulp and paper industries and bio-refining operations. It is available as the leading natural phenolic biopolymer in the market. It has chromophore functional groups and can absorb a broad spectrum of UV light in range of 250–400 nm. Using lignin as a natural ingredient in sunscreen cream, transparent film, paints, varnishes and microorganism protection has been actively investigated. Both in non-modified and modified forms, lignin provides enhancing UV protection of commercial products with less than a 10% blend with other material. In mixtures with other synthetic UV blockers, lignin indicated synergic effects and increased final UV blocking potential in compare with using only synthetic UV blocker or lignin. However, using lignin as a UV blocker is also challenging due to its complex structure, polydispersity in molecular weight, brownish color and some impurities that require more research in order to make it an ideal bio-based UV blocker.
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23
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Qiao Y, Dong H, Zhang X. A Versatile Sunscreen with Minimal ROS Damage and Low Permeability. ACS APPLIED MATERIALS & INTERFACES 2020; 12:6217-6225. [PMID: 31920066 DOI: 10.1021/acsami.9b18996] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Organic and inorganic ultraviolet (UV) filters possess themselves advantages, while they suffer from different limitations including photostability, penetration, and cytotoxicity. Integrating organic and inorganic UV filters in a single unit holds great potential for enhanced UV protection. Herein, the dendritic silicon dioxide microspheres (DSMs) are encapsulated with Bi2Ti2O7 nanocomposites (BTO-DSMs), an inorganic filter, and decorated with organic filters including sinapoyl malate (SM) and baicalin (BS/BTO-DSM) to enhance UV protection while significantly reducing ROS and skin permeability under UV exposure. The inorganic BTO-DSM component presents an expanded UV shield range and suppressed photocatalytic properties while preventing the organic filter SM direct contact with the epidermis and penetration behaviors. The baicalin efficiently scavenges the generated ROS from SM and reduces the transmittance of blue light. Notably, the results show that the proposed combined system significantly broadens the UV absorption region. Thus, the BS/BTO-DSM presents advanced in vitro anti-UV performance and in vivo UV protection against keratinocyte apoptosis and epidermal hyperplasia without long-term toxicity. The excellent anti-UV properties coupling with the suppressed photocatalytic capability and minimal epidermal penetration of BS/BTO-DSM make it promising for skin protection.
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Affiliation(s)
- Yuchun Qiao
- Research Center for Bioengineering and Sensing Technology and Beijing Advanced Innovation Center for Materials Genome Engineering , University of Science and Technology Beijing , 30 Xueyuan Road , Beijing 100083 , China
| | - Haifeng Dong
- Research Center for Bioengineering and Sensing Technology and Beijing Advanced Innovation Center for Materials Genome Engineering , University of Science and Technology Beijing , 30 Xueyuan Road , Beijing 100083 , China
| | - Xueji Zhang
- Research Center for Bioengineering and Sensing Technology and Beijing Advanced Innovation Center for Materials Genome Engineering , University of Science and Technology Beijing , 30 Xueyuan Road , Beijing 100083 , China
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Brożyna AA, Hoffman RM, Slominski AT. Relevance of Vitamin D in Melanoma Development, Progression and Therapy. Anticancer Res 2020; 40:473-489. [PMID: 31892603 PMCID: PMC6948187 DOI: 10.21873/anticanres.13976] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 10/22/2019] [Accepted: 10/30/2019] [Indexed: 12/11/2022]
Abstract
Melanoma is one of the most lethal types of skin cancer, with a poor prognosis once the disease enters metastasis. The efficacy of currently available treatment schemes for advanced melanomas is low, expensive, and burdened by significant side-effects. Therefore, there is a need to develop new treatment options. Skin cells are able to activate vitamin D via classical and non-classical pathways. Vitamin D derivatives have anticancer properties which promote differentiation and inhibit proliferation. The role of systemic vitamin D in patients with melanoma is unclear as epidemiological studies are not definitive. In contrast, experimental data have clearly shown that vitamin D and its derivatives have anti-melanoma properties. Furthermore, molecular and clinicopathological studies have demonstrated a correlation between defects in vitamin D signaling and progression of melanoma and disease outcome. Therefore, adequate vitamin D signaling can play a role in the treatment of melanoma.
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Affiliation(s)
- Anna A Brożyna
- Department of Human Biology, Institute of Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Toruń, Poland
| | | | - Andrzej T Slominski
- Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, U.S.A. .,Comprehensive Cancer Center, Cancer Chemoprevention Program, University of Alabama at Birmingham, Birmingham, AL, U.S.A.,VA Medical Center, Birmingham, AL, U.S.A
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25
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Jubran J, Sengelmann RD. High-risk squamous cell carcinoma and its impact on a 62-year-old male surgeon. BMJ Case Rep 2019; 12:12/8/e229940. [PMID: 31471358 DOI: 10.1136/bcr-2019-229940] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Cutaneous squamous cell carcinoma (cSCC) is a form of non-melanoma skin cancer responsible for more deaths in the USA than all other skin cancers combined. Some features, including anatomic site, are considered high risk in nature and pose a challenge for complete tumour removal. We present a case of a 62-year-old male surgeon with a multiply recurrent cSCC of the right conchal bowl. The tumour described herein was doubly recurrent to excision with a standard margin and could ultimately not be cleared with Mohs micrographic surgery. Ultimately, it necessitated auriculectomy and parotidectomy. This case exemplifies the pitfalls of traditional wide local excision with standard pathologic processing for high-risk cSCC.
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Affiliation(s)
- Jubran Jubran
- Santa Barbara Skin Institute, Santa Barbara, California, USA
| | - Roberta D Sengelmann
- Santa Barbara Skin Institute, Santa Barbara, California, USA.,Dermatology, Irvine School of Medicine, University of California, Irvine, California, USA
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Smith CJ. Pediatric Thermoregulation: Considerations in the Face of Global Climate Change. Nutrients 2019; 11:E2010. [PMID: 31454933 PMCID: PMC6770410 DOI: 10.3390/nu11092010] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 08/10/2019] [Accepted: 08/16/2019] [Indexed: 12/16/2022] Open
Abstract
Predicted global climate change, including rising average temperatures, increasing airborne pollution, and ultraviolet radiation exposure, presents multiple environmental stressors contributing to increased morbidity and mortality. Extreme temperatures and more frequent and severe heat events will increase the risk of heat-related illness and associated complications in vulnerable populations, including infants and children. Historically, children have been viewed to possess inferior thermoregulatory capabilities, owing to lower sweat rates and higher core temperature responses compared to adults. Accumulating evidence counters this notion, with limited child-adult differences in thermoregulation evident during mild and moderate heat exposure, with increased risk of heat illness only at environmental extremes. In the context of predicted global climate change, extreme environmental temperatures will be encountered more frequently, placing children at increased risk. Thermoregulatory and overall physiological strain in high temperatures may be further exacerbated by exposure to/presence of physiological and environmental stressors including pollution, ultraviolet radiation, obesity, diabetes, associated comorbidities, and polypharmacy that are more commonly occurring at younger ages. The aim of this review is to revisit fundamental differences in child-adult thermoregulation in the face of these multifaceted climate challenges, address emerging concerns, and emphasize risk reduction strategies for the health and performance of children in the heat.
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Affiliation(s)
- Caroline J Smith
- Department of Health and Exercise Science, Appalachian State University, Boone, NC 28608, USA.
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27
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Zhang H, Liu X, Fu S, Chen Y. Fabrication of Light-Colored Lignin Microspheres for Developing Natural Sunscreens with Favorable UV Absorbability and Staining Resistance. Ind Eng Chem Res 2019. [DOI: 10.1021/acs.iecr.9b02086] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Affiliation(s)
- Hui Zhang
- State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China
| | - Xinxin Liu
- State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China
| | - Shiyu Fu
- State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China
| | - Yuancai Chen
- State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China
- College of Environment and Energy, South China University of Technology, Guangzhou, Guangdong 510006, China
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28
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Wu S, Imokawa G. To be or not to be Photopigmented, that is the Question: An Introduction to the Special Issue dedicated to Photopigmentation and Melanoma. Photochem Photobiol 2019; 94:407-408. [PMID: 29878463 DOI: 10.1111/php.12933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Shiyong Wu
- Edison Biotechnology Institute, Ohio University, Athens, OH
| | - Genji Imokawa
- Center for Bioscience Research & Education, Utsunomiya University, Tochigi, Japan
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29
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Grandi V, di Gennaro P, Torrigiani S, Basco L, Lastrucci I, Pimpinelli N. Ingenol mebutate-mediated reduction in p53-positive keratinocytes in skin cancerization field directly correlates with clinical response in patients with multiple actinic keratoses. J Eur Acad Dermatol Venereol 2019; 33:1297-1303. [PMID: 30801837 DOI: 10.1111/jdv.15528] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Accepted: 01/18/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND UV radiation represents the main risk factor for non-melanoma skin cancers. Chronic UV exposure induces 'p53 patches', i.e. clonal outgrowths of keratinocytes with high nuclear expression of mutated p53, which might progress to actinic keratosis (AK) and ultimately squamous cell carcinomas (SCCs). AIMS Analysis of ingenol mebutate gel (150 and 500 mcg/g) effects in the reduction in 'p53 patches' inside skin cancerization field (CF) in patients with multiple AKs of face/scalp or trunk/extremities, in order to investigate whether the expected reduction in p53+ keratinocytes might have a direct role in the long-term AK reduction in treated areas. RESULTS We enrolled n = 10 patients, treated with ingenol mebutate and evaluated at 2 and 6 months after treatment. We observed clinical responses in the majority of patients (n = 7), with AK reduction or complete clearance (n = 6 and n = 1, respectively). Notably, two patients did not respond to the treatment, and in one patient, after initial partial response, new lesion was recorded. In untreated skin CF samples (n = 3), we observed numerous p53+ keratinocytes, similar to those observed in invasive SCC samples (53.56 ± 8.79 and 74.34 ± 22.05, respectively; P = 0.2). After treatment, we observed a variable p53+ keratinocyte reduction in CF samples at 2 months (24.67 ± 31.19; P = 0.19). Importantly, the amount of p53+ keratinocytes strongly and directly correlated with AK number (R2 = 0.81). CONCLUSION Untreated skin CF expresses high level of p53+ keratinocytes as invasive SCC. Ingenol mebutate is able to reduce p53+ keratinocytes with variable efficacy, this reduction degree directly correlating with clinical efficacy.
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Affiliation(s)
- V Grandi
- Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence School of Human Health Sciences, Florence, Italy
| | - P di Gennaro
- Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence School of Human Health Sciences, Florence, Italy.,Melanoma & Skin Cancer Unit, Tuscan Tumour Institute (ITT) - Santa Maria Annunziata Hospital, Central Tuscany District, Florence, Italy
| | - S Torrigiani
- Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence School of Human Health Sciences, Florence, Italy
| | - L Basco
- Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence School of Human Health Sciences, Florence, Italy
| | - I Lastrucci
- Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence School of Human Health Sciences, Florence, Italy
| | - N Pimpinelli
- Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence School of Human Health Sciences, Florence, Italy.,Melanoma & Skin Cancer Unit, Tuscan Tumour Institute (ITT) - Santa Maria Annunziata Hospital, Central Tuscany District, Florence, Italy
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30
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Wu D, Lai W, Lyu C, Hang H, Wang H. UHPLC-Q-TOF/MS detection of UV-induced TpT dimeric lesions in genomic DNA. J Chromatogr B Analyt Technol Biomed Life Sci 2018; 1096:135-142. [PMID: 30170291 DOI: 10.1016/j.jchromb.2018.08.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 07/21/2018] [Accepted: 08/19/2018] [Indexed: 12/18/2022]
Abstract
Ultraviolet (UV) radiation induces mutagenicity and cytotoxicity in human cells by the formation of DNA lesions, including cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), mainly on thymine-thymine (TpT) dinucleotides. Here, we firstly synthesized the two TpT dimeric lesions with satisfactory yields using a unique UV-irradiated water droplet approach followed by HPLC purification. By the use of purified TpT lesions as standards, we further developed and optimized a quantitative UHPLC-Q-TOF/MS method for the detection of CPDs and 6-4PPs. After the optimization of the enzyme composition and the pH values of hydrolysis solution, a combination of snake venom phosphodiesterase, nuclease P1, and calf intestine alkaline phosphatase can be used for one-step enzymatic digestion to efficiently release the dimeric lesions (CPDs and 6-4PPs) from the genomic DNA. By the use of the one-step digestion and UHPLC-Q-TOF/MS assay for scanning all dimeric lesions, we demonstrate that only are TpT dimeric lesions detectable in genomic DNA of HCT116 cells upon UVC irradiation. The estimated frequency of the CPD of TpT increases from 28.7 to 409 per 106 bases with increasing UVC dosage from 40 J/m2 to 1200 J/m2, while the 6-4PP of TpT increases from 3.7 to 54 per 106 bases. The proposed UHPLC-Q-TOF/MS method is promising for accurate identification and quantitative detection of UV-induced dimeric lesions in cellular DNA.
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Affiliation(s)
- Danni Wu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Weiyi Lai
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Cong Lyu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Haiying Hang
- Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Hailin Wang
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China.
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31
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Al-Eryani L, Jenkins SF, States VA, Pan J, Malone JC, Rai SN, Galandiuk S, Giri AK, States JC. miRNA expression profiles of premalignant and malignant arsenic-induced skin lesions. PLoS One 2018; 13:e0202579. [PMID: 30114287 PMCID: PMC6095593 DOI: 10.1371/journal.pone.0202579] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 08/06/2018] [Indexed: 12/21/2022] Open
Abstract
Arsenic, a naturally occurring element, contaminates the drinking water of over 200 million people globally. Chronic arsenic exposure causes multiple cancers including those originating from skin, lung and bladder, and is associated with liver, kidney, and prostate cancers. Skin is the primary target organ for arsenic toxicity; chronic toxicity initially manifests as non-malignant hyperkeratoses (HK) and subsequently advances to malignant lesions, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In this study, we evaluate the miRNA expression profiles of premalignant (3 HK) and malignant (3 BCC and 3 SCC) skin lesions from individuals chronically exposed to high levels of arsenic (59–172 ppb) in their drinking water in West Bengal, India. The lesions were histologically complex requiring histopathologic identification of keratinocytes to be isolated for RNA analyses. Keratinocytes were harvested using Laser Capture Microdissection and miRNA expression profiles were determined using TaqMan® Array Human MiRNA A Card v2.0. Thirty-five miRNAs were differentially expressed among the three lesion types analyzed. Two miRNAs (miR-425-5p and miR-433) were induced in both BCC and SCC relative to HK indicating their association with malignancy. Two other miRNAs (miR-184 and miR-576-3p) were induced in SCC relative to both BCC and HK suggesting selective induction in tumors capable of metastasis. Six miRNAs (miR-29c, miR-381, miR-452, miR-487b, miR-494 and miR-590-5p) were selectively suppressed in BCC relative to both SCC and HK. In conclusion, the differential miRNA expression was both phenotype- and stage-related. These miRNAs are potential biomarkers and may serve as therapy targets for arsenic-induced internal tumors.
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Affiliation(s)
- Laila Al-Eryani
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States of America
| | - Samantha F. Jenkins
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States of America
| | - Vanessa A. States
- Price Institute of Surgical Research, University of Louisville, Louisville, KY, United States of America
| | - Jianmin Pan
- Biostatistics Shared Facility, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, United States of America
| | - Janine C. Malone
- Department of Medicine, University of Louisville, Louisville, KY, United States of America
| | - Shesh N. Rai
- Biostatistics Shared Facility, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, United States of America
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, United States of America
| | - Susan Galandiuk
- Price Institute of Surgical Research, University of Louisville, Louisville, KY, United States of America
| | - Ashok K. Giri
- Molecular Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - J. Christopher States
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States of America
- * E-mail:
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A Jebar MA, Parisi AV, Downs NJ, Turner JF. Evaluated UVA Irradiances over a Twelve-year Period at a Subtropical Site from Ozone Monitoring Instrument Data Including the Influence of Cloud. Photochem Photobiol 2018; 94:1281-1288. [DOI: 10.1111/php.12948] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 05/25/2018] [Indexed: 12/01/2022]
Affiliation(s)
- Mustapha A. A Jebar
- Faculty of Health, Engineering and Sciences; University of Southern Queensland; Toowoomba Qld Australia
| | - Alfio V. Parisi
- Faculty of Health, Engineering and Sciences; University of Southern Queensland; Toowoomba Qld Australia
| | - Nathan J. Downs
- Faculty of Health, Engineering and Sciences; University of Southern Queensland; Toowoomba Qld Australia
| | - Joanna F. Turner
- Faculty of Health, Engineering and Sciences; University of Southern Queensland; Toowoomba Qld Australia
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33
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Hopf NB, Spring P, Hirt-Burri N, Jimenez S, Sutter B, Vernez D, Berthet A. Polycyclic aromatic hydrocarbons (PAHs) skin permeation rates change with simultaneous exposures to solar ultraviolet radiation (UV-S). Toxicol Lett 2018; 287:122-130. [DOI: 10.1016/j.toxlet.2018.01.024] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 01/26/2018] [Accepted: 01/30/2018] [Indexed: 12/28/2022]
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Nguyen TTL, Atwood SX. Illuminating Alternative Strategies to Treat Targeted Chemotherapy-Resistant Sporadic Basal Cell Carcinoma. J Invest Dermatol 2018; 138:1017-1019. [PMID: 29681387 DOI: 10.1016/j.jid.2017.11.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Revised: 11/14/2017] [Accepted: 11/17/2017] [Indexed: 10/17/2022]
Abstract
Sporadic and basal cell nevus syndrome basal cell carcinomas show differential response rates to Smoothened inhibitors. Chiang et al. demonstrate notable decreases in UV-induced mutagenesis, total mutation load, genomic instability, and drug-resistant mutations among basal cell nevus syndrome basal cell carcinomas using whole exome sequencing, which may explain the differences in drug response rates.
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Affiliation(s)
- Tuyen T L Nguyen
- Department of Developmental and Cell Biology, University of California, Irvine, California, USA
| | - Scott X Atwood
- Department of Developmental and Cell Biology, University of California, Irvine, California, USA; Department of Dermatology, University of California, Irvine, California, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, California, USA.
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Bertl J, Guo Q, Juul M, Besenbacher S, Nielsen MM, Hornshøj H, Pedersen JS, Hobolth A. A site specific model and analysis of the neutral somatic mutation rate in whole-genome cancer data. BMC Bioinformatics 2018; 19:147. [PMID: 29673314 PMCID: PMC5909259 DOI: 10.1186/s12859-018-2141-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 03/27/2018] [Indexed: 01/02/2023] Open
Abstract
Background Detailed modelling of the neutral mutational process in cancer cells is crucial for identifying driver mutations and understanding the mutational mechanisms that act during cancer development. The neutral mutational process is very complex: whole-genome analyses have revealed that the mutation rate differs between cancer types, between patients and along the genome depending on the genetic and epigenetic context. Therefore, methods that predict the number of different types of mutations in regions or specific genomic elements must consider local genomic explanatory variables. A major drawback of most methods is the need to average the explanatory variables across the entire region or genomic element. This procedure is particularly problematic if the explanatory variable varies dramatically in the element under consideration. Results To take into account the fine scale of the explanatory variables, we model the probabilities of different types of mutations for each position in the genome by multinomial logistic regression. We analyse 505 cancer genomes from 14 different cancer types and compare the performance in predicting mutation rate for both regional based models and site-specific models. We show that for 1000 randomly selected genomic positions, the site-specific model predicts the mutation rate much better than regional based models. We use a forward selection procedure to identify the most important explanatory variables. The procedure identifies site-specific conservation (phyloP), replication timing, and expression level as the best predictors for the mutation rate. Finally, our model confirms and quantifies certain well-known mutational signatures. Conclusion We find that our site-specific multinomial regression model outperforms the regional based models. The possibility of including genomic variables on different scales and patient specific variables makes it a versatile framework for studying different mutational mechanisms. Our model can serve as the neutral null model for the mutational process; regions that deviate from the null model are candidates for elements that drive cancer development. Electronic supplementary material The online version of this article (10.1186/s12859-018-2141-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Johanna Bertl
- Department of Molecular Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark.
| | - Qianyun Guo
- Department of Molecular Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
| | - Malene Juul
- Bioinformatics Research Centre, Aarhus University, C.F. Mollers Alle 8, Aarhus C, DK-8000, Denmark
| | - Søren Besenbacher
- Department of Molecular Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
| | - Morten Muhlig Nielsen
- Department of Molecular Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
| | - Henrik Hornshøj
- Department of Molecular Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
| | - Jakob Skou Pedersen
- Department of Molecular Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
| | - Asger Hobolth
- Department of Molecular Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
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The Mechanisms of Carnosol in Chemoprevention of Ultraviolet B-Light-Induced Non-Melanoma Skin Cancer Formation. Sci Rep 2018; 8:3574. [PMID: 29476131 PMCID: PMC5824785 DOI: 10.1038/s41598-018-22029-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 11/28/2017] [Indexed: 12/30/2022] Open
Abstract
Carnosol is a natural compound extracted from rosemary and sage, which has been demonstrated to have anti-inflammatory, anti-oxidant, and anti-cancer properties. In this report, we evaluated the therapeutic potential and elucidated the potential mechanism of action of carnosol in chemoprevention of ultraviolet B-light (UVB) induced non-melanoma skin cancer formation. Our data indicated that carnosol could partially reduce UVB-induced reactive oxygen species (ROS) elevation and thus reduce DNA damage. It could also reduce UVB-induced formation of cyclobutane pyrimidine dimers (CDP) in keratinocytes possibly through its ability in absorbing UVB radiation. In addition, carnosol could inhibit the UVB-induced activation of NF-κB and also reduce UVB-induced transformation of keratinocytes. Taken together, the results indicate the role of carnosol as a potential chemopreventive agent upon UVB radiation.
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Paolino G, Moliterni E, Corsetti P, Didona D, Bottoni U, Calvieri S, Mattozzi C. Vitamin D and melanoma: state of the art and possible therapeutic uses. GIORN ITAL DERMAT V 2017; 154:64-71. [PMID: 29249122 DOI: 10.23736/s0392-0488.17.05801-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun-exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.
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Affiliation(s)
| | | | | | - Dario Didona
- Division of Dermatology, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy
| | - Ugo Bottoni
- Department of Dermatology, Magna Grecia University, Catanzaro, Italy
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Ombra MN, Paliogiannis P, Doneddu V, Sini MC, Colombino M, Rozzo C, Stanganelli I, Tanda F, Cossu A, Palmieri G. Vitamin D status and risk for malignant cutaneous melanoma: recent advances. Eur J Cancer Prev 2017; 26:532-541. [PMID: 28125434 PMCID: PMC5627529 DOI: 10.1097/cej.0000000000000334] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Accepted: 12/07/2016] [Indexed: 01/08/2023]
Abstract
Cutaneous malignant melanoma, whose incidence is increasing steadily worldwide, is the result of complex interactions between individual genetic factors and environmental risk factors. Ultraviolet radiation represents the most important environmental risk factor for the development of skin cancers, including melanoma. Sun exposure and early sunburn during childhood are the principal causes of cutaneous melanoma insurgence in adults, with double the risk relative to a nonexposed population. Consequently, ultraviolet protection has long been recognized as an important measure to prevent such a malignancy. Biological and epidemiological data suggest that vitamin D status could affect the risk of cancer and play a role in cancer prevention by exerting antiproliferative effects. Solar radiations are critical for vitamin D synthesis in humans; however, uncontrolled and intensive sun exposure is dangerous to skin health and may contribute toward the development of cutaneous malignant melanoma. An optimum balance between sun protection and exposure is thus advocated. Additional research is required to confirm the preventive role of vitamin D in melanoma incidence or a positive influence on patient outcome.
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Affiliation(s)
- Maria N. Ombra
- Institute of Food Sciences, National Research Council (CNR), Avellino
| | | | - Valentina Doneddu
- Department of Surgical, Microsurgical and Medical Sciences, University of Sassari
| | - Maria C. Sini
- Institute of Biomolecular Chemistry, National Research Council (CNR), Cancer Genetics Unit, Sassari
| | - Maria Colombino
- Institute of Biomolecular Chemistry, National Research Council (CNR), Cancer Genetics Unit, Sassari
| | - Carla Rozzo
- Institute of Biomolecular Chemistry, National Research Council (CNR), Cancer Genetics Unit, Sassari
| | - Ignazio Stanganelli
- Romagna Scientific Institute for the Study and Cure of Tumors, Skin Cancer Unit, Meldola, Italy
| | - Francesco Tanda
- Department of Surgical, Microsurgical and Medical Sciences, University of Sassari
| | - Antonio Cossu
- Department of Surgical, Microsurgical and Medical Sciences, University of Sassari
| | - Giuseppe Palmieri
- Institute of Biomolecular Chemistry, National Research Council (CNR), Cancer Genetics Unit, Sassari
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Li YL, Wei F, Li YP, Zhang LH, Bai YZ. A case-control study on association of nucleotide excision repair polymorphisms and its interaction with environment factors with the susceptibility to non-melanoma skin cancer. Oncotarget 2017; 8:80994-81000. [PMID: 29113361 PMCID: PMC5655256 DOI: 10.18632/oncotarget.20942] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 07/19/2017] [Indexed: 12/24/2022] Open
Abstract
Aims To investigate the association of several single nucleotide polymorphisms (SNPs) within nucleotide excision repair (NER) gene and additional gene- gene and gene- smoking interaction with non-melanoma skin cancer (NMSC) risk in a Chinese population. Methods A total of 1322 participants (939 males, 383 females) were selected, including 660 NMSC patients and 662 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association between 4 SNPs within NER gene, additional gene- gene and gene- smoking interaction on NMSC risk. Results NMSC risk was significantly higher in carriers with G allele of rs2228527 than those with AA genotype (AG + GG versus AA), adjusted OR (95%CI) =1.76 (1.24-2.37), and higher in carriers with the G allele of rs2228529 than those with AA genotype (AG + GG versus AA), adjusted OR (95%CI) = 1.66 (1.24-2.13). However, we did not find any direct association of the rs4134822 and rs1799793 with NMSC risk after covariates adjustment. GMDR model indicated a significant interaction combination (p=0.0010), including rs2228529 and current smoking. Overall, the cross-validation consistency of this model was 9/ 10, and the testing accuracy was 60.72%. Current smokers with rs2228529- GA or GG genotype have the highest NMSC risk, compared to never- smokers with rs2228529- AA genotype, OR (95%CI) = 2.92 (1.61-4.29). Conclusions We found that the G allele of rs2228527 and the G allele of rs2228529 within NER gene, interaction between rs2228529 and current smoking were all associated with increased NMSC risk.
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Affiliation(s)
- Yan-Ling Li
- Department of Dermatology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China
| | - Feng Wei
- Department of Dermatology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China
| | - Yu-Ping Li
- Department of Dermatology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China
| | - Li-Hua Zhang
- Department of Dermatology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China
| | - Yan-Zhi Bai
- Department of Dermatology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China
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Gillen MM, Markey CH. Beauty and the burn: tanning and other appearance-altering attitudes and behaviors. PSYCHOL HEALTH MED 2017; 22:1271-1277. [PMID: 28537192 DOI: 10.1080/13548506.2017.1330544] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Tanning is often prompted by appearance concerns, yet little is known about associations between tanning and other appearance-altering behaviors. In the current study, we examined potential correlates of indoor and outdoor tanning that, like tanning, may enhance appearance but present health risks. College students (N = 284; Mage = 20.14, SD = 3.39) completed a survey. The main outcome measures were indoor tanning and outdoor sunbathing. Participants also answered questions pertaining to piercings and tattoos, healthy and unhealthy dieting behaviors, cigarette smoking, and interest in cosmetic surgery and enhancements. Results indicate that indoor tanners were more likely to have piercings, tattoos, to engage in healthy dieting behaviors, and to express interest in cosmetic enhancements. Outdoor sunbathers were more interested in cosmetic enhancements than non-outdoor sunbathers, and female outdoor sunbathers reported more unhealthy dieting behaviors than male outdoor sunbathers. These findings provide evidence for college students' engagement in a constellation of appearance-oriented risk behaviors.
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Affiliation(s)
- Meghan M Gillen
- a Division of Social Sciences , The Pennsylvania State University , Abington , PA , USA
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Jatana S, Palmer BC, Phelan SJ, Gelein R, DeLouise LA. In vivo quantification of quantum dot systemic transport in C57BL/6 hairless mice following skin application post-ultraviolet radiation. Part Fibre Toxicol 2017; 14:12. [PMID: 28410606 PMCID: PMC5391571 DOI: 10.1186/s12989-017-0191-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 03/27/2017] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Previous work has demonstrated size, surface charge and skin barrier dependent penetration of nanoparticles into the viable layers of mouse skin. The goal of this work was to characterize the tissue distribution and mechanism of transport of nanoparticles beyond skin, with and without Ultraviolet Radiation (UVR) induced skin barrier disruption. Atomic absorption spectroscopy (AAS), flow cytometry and confocal microscopy were used to examine the effect of UVR dose (180 and 360 mJ/cm2 UVB) on the skin penetration and systemic distribution of quantum dot (QD) nanoparticles topically applied at different time-points post UVR using a hairless C57BL/6 mouse model. RESULTS Results indicate that QDs can penetrate mouse skin, regardless of UVR exposure, as evidenced by the increased cadmium in the local lymph nodes of all QD treated mice. The average % recovery for all treatment groups was 69.68% with ~66.84% of the applied dose recovered from the skin (both epicutaneous and intracutaneous). An average of 0.024% of the applied dose was recovered from the lymph nodes across various treatment groups. When QDs are applied 4 days post UV irradiation, at the peak of the skin barrier defect and LC migration to the local lymph node, there is an increased cellular presence of QD in the lymph node; however, AAS analysis of local lymph nodes display no difference in cadmium levels due to UVR treatment. CONCLUSIONS Our data suggests that Langerhans cells (LCs) can engulf QDs in skin, but transport to the lymph node may occur by both cellular (dendritic and macrophage) and non-cellular mechanisms. It is interesting that these specific nanoparticles were retained in skin similarly regardless of UVR barrier disruption, but the observed skin immune cell interaction with nanoparticles suggest a potential for immunomodulation, which we are currently examining in a murine model of skin allergy.
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Affiliation(s)
- Samreen Jatana
- Department of Biomedical Engineering, University of Rochester, Rochester, NY USA
| | - Brian C. Palmer
- Department of Environmental Medicine, University of Rochester Medical Center, New York, USA
| | - Sarah J. Phelan
- Department of Environmental Medicine, University of Rochester Medical Center, New York, USA
| | - Robert Gelein
- Department of Environmental Medicine, University of Rochester Medical Center, New York, USA
| | - Lisa A. DeLouise
- Department of Biomedical Engineering, University of Rochester, Rochester, NY USA
- Department of Dermatology, University of Rochester Medical Center, Dermatology and Biomedical Engineering, 601 Elmwood Avenue, Box 697, Rochester, NY 14642 USA
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GenePANDA-a novel network-based gene prioritizing tool for complex diseases. Sci Rep 2017; 7:43258. [PMID: 28252032 PMCID: PMC5333103 DOI: 10.1038/srep43258] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 01/23/2017] [Indexed: 02/08/2023] Open
Abstract
Here we describe GenePANDA, a novel network-based tool for prioritizing candidate disease genes. GenePANDA assesses whether a gene is likely a candidate disease gene based on its relative distance to known disease genes in a functional association network. A unique feature of GenePANDA is the introduction of adjusted network distance derived by normalizing the raw network distance between two genes with their respective mean raw network distance to all other genes in the network. The use of adjusted network distance significantly improves GenePANDA’s performance on prioritizing complex disease genes. GenePANDA achieves superior performance over five previously published algorithms for prioritizing disease genes. Finally, GenePANDA can assist in prioritizing functionally important SNPs identified by GWAS.
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Kudr J, Richtera L, Xhaxhiu K, Hynek D, Heger Z, Zitka O, Adam V. Carbon dots based FRET for the detection of DNA damage. Biosens Bioelectron 2017; 92:133-139. [PMID: 28213325 DOI: 10.1016/j.bios.2017.01.067] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2016] [Revised: 01/28/2017] [Accepted: 01/30/2017] [Indexed: 12/19/2022]
Abstract
Here, we aimed our attention at the synthesis of carbon dots (C-dots) with the ability to interact with DNA to suggest an approach for the detection of DNA damage. Primarily, C-dots modified with amine moieties were synthesized using the one-step microwave pyrolysis of citric acid in the presence of diethylenetriamine. The C-dots showed strong photoluminescence with a quantum yield of 4%. In addition, the C-dots (2.8±0.8nm) possessed a good colloidal stability and exhibited a positive surface charge (ζ=36mV) at a neutral pH. An interaction study of the C-dots and the DNA fragment of λ bacteriophage was performed, and the DNA binding resulted in changes to the photoluminescent and absorption properties of the C-dots. A binding of the C-dots to DNA was also observed as a change to DNA electrophoretic mobility and a decreased ability to intercalate ethidium bromide (EtBr). Moreover, the Förster (or fluorescence) resonance energy transfer (FRET) between the C-dots and EtBr was studied, in which the C-dots serve as an excitation energy donor and the EtBr serves as an acceptor. When DNA was damaged using ultraviolet (UV) radiation (λ=254nm) and hydroxyl radicals, the intensity of the emitted photoluminescence at 612nm significantly decreased. The concept was proved on analysis of the genomic DNA from PC-3 cells and DNA isolated from melanoma tissues.
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Affiliation(s)
- Jiri Kudr
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czechia
| | - Lukas Richtera
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czechia; Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czechia
| | - Kledi Xhaxhiu
- Department of Chemistry, Faculty of Natural Sciences, University of Tirana, Blv. Zog I, No. 2/1, 1001 Tirana, Albania
| | - David Hynek
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czechia; Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czechia
| | - Zbynek Heger
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czechia; Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czechia
| | - Ondrej Zitka
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czechia; Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czechia
| | - Vojtech Adam
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czechia; Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czechia.
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Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma. mBio 2017; 8:mBio.02079-16. [PMID: 28049147 PMCID: PMC5210499 DOI: 10.1128/mbio.02079-16] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Merkel cell polyomavirus is the primary etiological agent of the aggressive skin cancer Merkel cell carcinoma (MCC). Recent studies have revealed that UV radiation is the primary mechanism for somatic mutagenesis in nonviral forms of MCC. Here, we analyze the whole transcriptomes and genomes of primary MCC tumors. Our study reveals that virus-associated tumors have minimally altered genomes compared to non-virus-associated tumors, which are dominated by UV-mediated mutations. Although virus-associated tumors contain relatively small mutation burdens, they exhibit a distinct mutation signature with observable transcriptionally biased kataegic events. In addition, viral integration sites overlap focal genome amplifications in virus-associated tumors, suggesting a potential mechanism for these events. Collectively, our studies indicate that Merkel cell polyomavirus is capable of hijacking cellular processes and driving tumorigenesis to the same severity as tens of thousands of somatic genome alterations. A variety of mutagenic processes that shape the evolution of tumors are critical determinants of disease outcome. Here, we sequenced the entire genome of virus-positive and virus-negative primary Merkel cell carcinomas (MCCs), revealing distinct mutation spectra and corresponding expression profiles. Our studies highlight the strong effect that Merkel cell polyomavirus has on the divergent development of viral MCC compared to the somatic alterations that typically drive nonviral tumorigenesis. A more comprehensive understanding of the distinct mutagenic processes operative in viral and nonviral MCCs has implications for the effective treatment of these tumors.
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Ye Y, Sun-Waterhouse D, You L, Abbasi AM. Harnessing food-based bioactive compounds to reduce the effects of ultraviolet radiation: a review exploring the link between food and human health. Int J Food Sci Technol 2016. [DOI: 10.1111/ijfs.13344] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
- Yuhui Ye
- School of Food Science and Engineering; South China University of Technology; Guangzhou 510640 China
| | - Dongxiao Sun-Waterhouse
- School of Food Science and Engineering; South China University of Technology; Guangzhou 510640 China
| | - Lijun You
- School of Food Science and Engineering; South China University of Technology; Guangzhou 510640 China
| | - Arshad Mehmood Abbasi
- School of Food Science and Engineering; South China University of Technology; Guangzhou 510640 China
- Department of Environmental Sciences; COMSATS Institute of Information Technology (CIIT); Park Road ChakShahzad Islamabad 22060 Pakistan
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Abstract
Renal insufficiency is highly prevalent among cancer patients, which negatively impacts on their survival. Furthermore, many oncological treatments may severely impair kidney function or exasperate preexisting renal diseases. Thus, the relationship between cancer and the kidney could be regarded as “circular” and warrants specific competencies and expertise for its management. This is why onco-nephrology, as a subspecialty of both oncology and nephrology, has begun to gain importance over the past few years. The complex issues of the management of cancer patients in dialysis, of candidates for kidney transplantation who have had a previous malignancy, and of transplant recipients who subsequently develop a malignancy, also fall into the field of onco-nephrology.
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Vand-Rajabpour F, Sadeghipour N, Saee-Rad S, Fathi H, Noormohammadpour P, Yaseri M, Hesari KK, Bagherpour Z, Tabrizi M. Differential BMI1, TWIST1, SNAI2 mRNA expression pattern correlation with malignancy type in a spectrum of common cutaneous malignancies: basal cell carcinoma, squamous cell carcinoma, and melanoma. Clin Transl Oncol 2016; 19:489-497. [PMID: 27718152 DOI: 10.1007/s12094-016-1555-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Accepted: 09/22/2016] [Indexed: 02/01/2023]
Abstract
PURPOSE Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) can be used as a unique model to identify molecular mechanisms to distinguish rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma) cancer. It is known that epithelial-mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers. We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma) would be a unique cancer model system to elucidate steps toward cancer invasion and metastasis. METHODS We evaluated the mRNA expression level of BMI1, TWIST1, and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along with normal tissue samples. RESULTS We demonstrate downregulation of BMI1 mRNA expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001), and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA expression is represented in melanoma samples compared with controls (p = 0.022) and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients with positive history of cancers. Extremely low mRNA expression of BMI1 is detected in patients with positive history of cancers other than skin cancer. CONCLUSIONS These findings provide support for the hypothesis that the spectrum of cutaneous cancers could be better understood as a series of gene dosage-dependent entities with distinct molecular events. Oncogene-induced senescence, mechanism of which is still unclear, could be one explanation for these results.
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Affiliation(s)
- F Vand-Rajabpour
- Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, P.O. Box 14155-6447, Tehran, 14176-13151, Iran
| | - N Sadeghipour
- Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, P.O. Box 14155-6447, Tehran, 14176-13151, Iran
| | - S Saee-Rad
- Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - H Fathi
- Plastic, Reconstructive and Aesthetic Surgery Department, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Tumor Clinic, Pathology Department and the Department of Plastic and Reconstructive Surgery, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - P Noormohammadpour
- Tumor Clinic, Pathology Department and the Department of Plastic and Reconstructive Surgery, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - M Yaseri
- Epidemiology and Biostatistics Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - K K Hesari
- Tumor Clinic, Pathology Department and the Department of Plastic and Reconstructive Surgery, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Z Bagherpour
- Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, P.O. Box 14155-6447, Tehran, 14176-13151, Iran
| | - M Tabrizi
- Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, P.O. Box 14155-6447, Tehran, 14176-13151, Iran.
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Erlendsson AM, Thaysen-Petersen D, Bay C, Hald A, Skak K, Zibert JR, Paasch U, Wulf HC, Haedersdal M. Repeated Treatments with Ingenol Mebutate Prevents Progression of UV-Induced Photodamage in Hairless Mice. PLoS One 2016; 11:e0162597. [PMID: 27636884 PMCID: PMC5026374 DOI: 10.1371/journal.pone.0162597] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 08/25/2016] [Indexed: 01/07/2023] Open
Abstract
Background and Aim Ingenol mebutate (IngMeb) is an effective treatment for actinic keratosis. In this study, we hypothesized that repeated treatments with IngMeb may prevent progression of UV-induced photodamage, and that concurrent application of a corticosteroid may reduce IngMeb-induced local skin responses (LSR). Methods Hairless mice (n = 60; 3 groups of 20 mice) were irradiated with solar simulated ultraviolet radiation (UVR) throughout the study. Five single treatments with IngMeb were given at 4-week intervals (Days 21, 49, 77, 105, and 133). Clobetasol propionate (CP) was applied once daily for 5 days prior to each IngMeb application, as well as 6 h and 1 day post treatment. One week after IngMeb treatment No. 1, 3, and 5 (Days 28, 84, and 140), biopsies from four mice in each group were collected for histological evaluation of UV-damage on a standardized UV-damage scale (0–12). LSR (0–24) were assessed once daily (Days 1–7) after each IngMeb treatment. Results IngMeb prevented progression of photodamage in terms of keratosis grade, epidermal hypertrophy, dysplasia, and dermal actinic damage with a lower composite UV-damage score on day 140 (UVR 10.25 vs. UVR+IngMeb 6.00, p = 0.002) compared to UVR alone. IngMeb induced LSR, including erythema, flaking, crusting, bleeding, vesiculation, and ulceration. Concurrent CP increased LSR (max LSR Tx 1–5: UVR+IngMeb+CP 3.6–5.5 vs. UVR+IngMeb 2.6–4.3) and provided better prevention of photodamage compared to IngMeb alone (Day 140: UVR+IngMeb 6.00 vs. UVR+IngMeb+CP 3.00 p < 0.001). Conclusion Repeated field-directed treatments with IngMeb prevent progression of cutaneous photodamage in hairless mice, while CP cannot be used to alleviate IngMeb-induced LSR. The findings suggest that IngMeb may potentially serve as a prophylactic treatment for UV-induced tumors.
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Affiliation(s)
- Andrés Már Erlendsson
- Department of Dermatology, Bispebjerg University Hospital, Copenhagen, Denmark
- * E-mail:
| | | | - Christiane Bay
- Department of Dermatology, Bispebjerg University Hospital, Copenhagen, Denmark
| | | | | | | | - Uwe Paasch
- Department of Dermatology, Division of Aesthetics and Laserdermatology, University of Leipzig, Leipzig, Germany
| | - Hans Christian Wulf
- Department of Dermatology, Bispebjerg University Hospital, Copenhagen, Denmark
| | - Merete Haedersdal
- Department of Dermatology, Bispebjerg University Hospital, Copenhagen, Denmark
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Morales-Sánchez MA, Peralta-Pedrero ML, Jurado-Santa Cruz F, Pomerantz H, Barajas-Nava LA. Interventions for preventing keratinocyte cancer in high-risk groups not receiving immunosuppressive therapy. Hippokratia 2016. [DOI: 10.1002/14651858.cd012266] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Martha Alejandra Morales-Sánchez
- Dermatological Center, "Dr. Ladislao de la Pascua"; Education and Research Unit; Dr. José María Vértiz No. 464 Col. Buenos Aires México City Mexico 06780
| | - María Luisa Peralta-Pedrero
- Dermatological Center, "Dr. Ladislao de la Pascua"; Education and Research Unit; Dr. José María Vértiz No. 464 Col. Buenos Aires México City Mexico 06780
| | - Fermín Jurado-Santa Cruz
- Dermatological Center, "Dr. Ladislao de la Pascua"; Education and Research Unit; Dr. José María Vértiz No. 464 Col. Buenos Aires México City Mexico 06780
| | - Hyemin Pomerantz
- Hofstra Northwell School of Medicine; Department of Dermatology; Hempstead New York USA
| | - Leticia A Barajas-Nava
- Hospital Infantil de México Federico Gómez (HIMFG), Health National Institute; Evidence-Based Medicine Research Unit; Dr. Márquez #162 Col. Doctores, Del. Cuauhtémoc México City Mexico 06720
- Iberoamerican Cochrane Network; Institute of Biomedical Research (IIB Sant Pau), C/ Sant Antoni Ma Claret 171 Casa de Convalescència Barcelona Barcelona Spain 08041
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Ultraviolet Radiation-Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging. Stem Cells Int 2016; 2016:7370642. [PMID: 27148370 PMCID: PMC4842382 DOI: 10.1155/2016/7370642] [Citation(s) in RCA: 198] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 03/14/2016] [Indexed: 12/11/2022] Open
Abstract
Skin is the largest human organ. Skin continually reconstructs itself to ensure its viability, integrity, and ability to provide protection for the body. Some areas of skin are continuously exposed to a variety of environmental stressors that can inflict direct and indirect damage to skin cell DNA. Skin homeostasis is maintained by mesenchymal stem cells in inner layer dermis and epidermal stem cells (ESCs) in the outer layer epidermis. Reduction of skin stem cell number and function has been linked to impaired skin homeostasis (e.g., skin premature aging and skin cancers). Skin stem cells, with self-renewal capability and multipotency, are frequently affected by environment. Ultraviolet radiation (UVR), a major cause of stem cell DNA damage, can contribute to depletion of stem cells (ESCs and mesenchymal stem cells) and damage of stem cell niche, eventually leading to photoinduced skin aging. In this review, we discuss the role of UV-induced DNA damage and oxidative stress in the skin stem cell aging in order to gain insights into the pathogenesis and develop a way to reduce photoaging of skin cells.
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