-
1.
A Critical Appraisal of the Recent Reports on Sunbeds from the European Commission's Scientific Committee on Health, Environmental and Emerging Risks and from the World Health Organization.
Reichrath, J, Lindqvist, PG, DE Gruijl, FR, Pilz, S, Kimball, SM, Grant, WB, Holick, MF
Anticancer research. 2018;(2):1111-1120
Abstract
The European Commission's Scientific Committee on Health, Environmental and Emerging Risks and the World Health Organization recently published reports which concluded that a large proportion of melanoma and non-melanoma skin cancer is attributable to sunbed use, and that there is no need to use sunbeds as there are no health benefits and they are not needed to achieve an optimal vitamin D level. The overall conclusion from both bodies was that there is no safe limit for UV irradiance from sunbeds. We are, however, deeply concerned that these assessments appear to be based on an incomplete, unbalanced and non-critical evaluation of the literature. Therefore, we rebut these conclusions by addressing the incomplete analysis of the adverse health effects of UV and sunbed exposure (what is 'safe'?) and the censored representation of beneficial effects, not only but especially from vitamin D production. The stance taken by both agencies is not sufficiently supported by the data and in particular, current scientific knowledge does not support the conclusion sunbed use increases melanoma risk.
-
2.
Botanical Therapeutics: Phytochemical Screening and Biological Assessment of Chamomile, Parsley and Celery Extracts against A375 Human Melanoma and Dendritic Cells.
Danciu, C, Zupko, I, Bor, A, Schwiebs, A, Radeke, H, Hancianu, M, Cioanca, O, Alexa, E, Oprean, C, Bojin, F, et al
International journal of molecular sciences. 2018;(11)
Abstract
Chamomile, parsley, and celery represent major botanical sources of apigenin, a well-known flavone with chemopreventive properties. The aim of this study was to assess the phytochemical composition, antioxidant, and anti-inflammatory potential of methanol extracts obtained from chamomile, parsley, and celery collected from Romania, as well as the biological activity against A375 human melanoma and human dendritic cells. Results have shown that all three extracts are rich in polyphenolic compounds and flavonoids, and they generate a radical scavenger capacity, iron chelation potential, as well as lipoxygenase inhibition capacity. Chamomile and celery extracts present weak antiproliferative and pro-apoptotic properties in the set experimental conditions, while parsley extract draws out significant pro-apoptotic potential against A375 human melanoma cells. Parsley and chamomile extracts affected the fibroblast-like morphology of the screened tumor cell line. On the other hand, chamomile and celery extracts abrogated the expansion of LPS-activated dendritic cells, while the metabolic activity was attenuated by stimulation with celery extract; chamomile and parsley extracts had no effect upon this parameter. Chamomile and parsley extracts incubation with naive dendritic cells did not trigger cytokine secretion (TNF-alpha, IL-6, IL-10), but celery extract stimulation significantly reduced the anti-inflammatory, cytokine IL-10.
-
3.
Caffeinated and decaffeinated coffee consumption and melanoma risk: a dose-response meta-analysis of prospective cohort studies.
Micek, A, Godos, J, Lafranconi, A, Marranzano, M, Pajak, A
International journal of food sciences and nutrition. 2018;(4):417-426
Abstract
To determine the association between total, caffeinated and decaffeinated coffee consumption and melanoma risk a dose-response meta-analysis on prospective cohort studies were performed. Eligible studies were identified searching PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by random-effects meta-analysis and the shape of the exposure-outcome curve was modelled linearly and using restricted cubic splines. A total of seven studies eligible for meta-analysis were identified that comprised 1,418,779 participants and 9211 melanoma cases. A linear dose-response meta-analysis showed a significant association between total coffee consumption and melanoma risk. An increase in coffee consumption of one cup per day was associated with a 3% reduction in melanoma risk (RR 0.97; 95% CI 0.95-0.99). Our findings suggest that coffee intake may be inversely associated with incidence of melanoma. Nevertheless, further studies exploring also the role of confounding factors are needed to explain the heterogeneity among studies.
-
4.
Oleuropein, the Main Polyphenol of Olea europaea Leaf Extract, Has an Anti-Cancer Effect on Human BRAF Melanoma Cells and Potentiates the Cytotoxicity of Current Chemotherapies.
Ruzzolini, J, Peppicelli, S, Andreucci, E, Bianchini, F, Scardigli, A, Romani, A, la Marca, G, Nediani, C, Calorini, L
Nutrients. 2018;(12)
Abstract
Oleuropein (Ole), a secoiridoid glucoside present in Olea europaea leaves, gained scientific interest thanks to its several biological properties, including the anticancer one. We verified whether Ole might potentiate the cytotoxicity of conventional drugs used to treat melanoma, disclosing a potentially new therapeutic strategy. We tested the cytotoxic action of Ole alone or in combination with chemotherapeutics on A375 human melanoma cells. We found that Ole was able, at a dose of 500 µM, to stimulate apoptosis, while at a non-toxic dose of 250 µM, it affected cell proliferation and induced the downregulation of the pAKT/pS6 pathway. A dose of 250 µM Ole did not potentiate the effect of Vemurafenib (PLX4032), but it succeeded in increasing the cytotoxic effect of Dacarbazine (DTIC). The major effect was found in the association between Ole and Everolimus (RAD001), also on PLX4032-resistant BRAF melanoma cells, which possibly cooperate in the inhibition of the pAKT/pS6 pathway. Of interest, an olive leaf extract enriched in equimolar Ole was more effective and able to further improve DTIC and RAD001 efficacy on BRAF melanoma cells with respect to Ole alone. Therefore, Ole represents a natural product able to potentiate a wide array of chemotherapeutics against BRAF melanoma cells affecting the pAKT/pS6 pathway.
-
5.
Epigenetics of skin cancer: Interventions by selected bioactive phytochemicals.
Penta, D, Somashekar, BS, Meeran, SM
Photodermatology, photoimmunology & photomedicine. 2018;(1):42-49
Abstract
The prevalence and risk of skin cancer have been increasing over past three decades. Two major types of skin cancer observed in humans are melanoma and nonmelanoma. Nonmelanoma further subdivided into basal cell carcinoma and squamous cell carcinoma. Melanoma arises from melanocyte which locates at the bottom layer of skin epidermis, which primarily protects the skin from being exposed to external factors. Melanoma is less common among all other types of skin cancers but causes higher mortality. Epigenetic regulation associated with the transcriptional activation and inactivation of genes plays a major role in various disease progression including skin cancer. The major epigenetic changes observed at cellular level include DNA methylation, histone modifications, and miRNA-mediated gene regulation. The aberrant pattern in these epigenetic processes leads to altered expression of several genes involved in cell cycle, cell proliferation, cell motility, and apoptosis. Several natural bioactive phytochemicals have been shown to exhibit epigenetic modulatory capability and act as chemopreventive as well as therapeutic agents. In this review, we mainly discuss the major epigenetic modifications observed in melanoma and the epigenetic modulatory role of selected bioactive phytochemicals against the skin cancer.
-
6.
Vitamin D in melanoma: Controversies and potential role in combination with immune check-point inhibitors.
Stucci, LS, D'Oronzo, S, Tucci, M, Macerollo, A, Ribero, S, Spagnolo, F, Marra, E, Picasso, V, Orgiano, L, Marconcini, R, et al
Cancer treatment reviews. 2018;:21-28
Abstract
The role of vitamin D in melanoma is still controversial. Although several Authors described a correlation between vitamin D deficiency and poor survival in metastatic melanoma patients, clinical trials exploring the effects of vitamin D supplementation in this clinical setting were mostly inconclusive. However, recent evidence suggests that vitamin D exerts both anti-proliferative effects on tumor cells and immune-modulating activities, that have been widely explored in auto-immune disorders. On the one hand, vitamin D has been shown to inhibit T-helper17 lymphocytes, notoriously involved in the pathogenesis of immune-related adverse events (iAEs) which complicate immune-checkpoint inhibitor (ICI) treatment. On the other hand, vitamin D up-regulates PDL-1 expression on both epithelial and immune cells, suggesting a synergic effect in combination with ICIs, for which further investigation is needed.
-
7.
Use of Antihypertensive Drugs and Risk of Malignant Melanoma: A Meta-analysis of Observational Studies.
Tang, H, Fu, S, Zhai, S, Song, Y, Han, J
Drug safety. 2018;(2):161-169
-
-
Free full text
-
Abstract
INTRODUCTION Several antihypertensive drugs are photosensitizing and may promote the development of malignant melanoma (MM), but evidence remains inconsistent. We sought to quantify the association between use of antihypertensive drugs and MM risk. METHODS We systematically searched PubMed, Embase, and CENTRAL from inception to August 17, 2017 to identify observational studies that reported the MM risk associated with the use of antihypertensive drugs. A random-effects meta-analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI). RESULTS Overall, we included eight observational studies (two cohort studies and six case-control studies). Compared with non-use, use of diuretics (OR 1.10; 95% CI 1.03-1.17) or β-adrenergic blocking agents (OR 1.19; 95% CI 1.04-1.37) was significantly associated with increased risk of MM. The use of angiotensin-converting enzyme inhibitors (OR 1.08; 95% CI 0.95-1.23), angiotensin II receptor blockers (OR 1.12; 95% CI 0.95-1.31), and calcium channel blockers (OR 1.12; 95% CI 0.72-1.74) was not significantly associated with increased risk of MM. CONCLUSIONS Current evidence from observational studies suggests that use of diuretics or β-adrenergic blocking agents may be associated with increased risk of MM. Further large well-conducted prospective studies are required to confirm our findings.
-
8.
Alcohol, alcoholic beverages, and melanoma risk: a systematic literature review and dose-response meta-analysis.
Gandini, S, Masala, G, Palli, D, Cavicchi, B, Saieva, C, Ermini, I, Baldini, F, Gnagnarella, P, Caini, S
European journal of nutrition. 2018;(7):2323-2332
Abstract
PURPOSE Several studies in recent years have investigated the relationship between alcohol intake and melanoma risk, with conflicting results. To help clarify this issue, we conducted a literature review and dose-response meta-analysis of studies published until June 30th, 2017, that examined the association between alcohol intake (overall and by beverage type) and melanoma risk. METHODS We used random effect models with maximum likelihood estimation to calculate summary relative risk (SRR) and 95% confidence intervals (95%CI). RESULTS We included 20 independent studies (encompassing 10,555 melanoma cases and over 1.6 million non-cases/controls) published during 1986-2016, of which six had a prospective cohort study design. Adjustment for phenotypic characteristics and sunlight exposure was performed in 11 and nine studies, respectively. Alcohol intake was moderately associated with melanoma risk: the SRR were 1.29 (95% CI 1.14-1.45) for those in the highest vs. lowest category of current alcohol intake, and 1.96 (95% CI 1.02-3.76, I2 = 0%) for cumulative intake. In the dose-response analysis, the increase in risk associated with a 10 g increment in daily alcohol intake was 1.07 (95% CI 1.03-1.11). Risk estimates did not differ by gender, study design and adjustment for confounders; between-studies heterogeneity was acceptable, and there was no evidence of publication bias. CONCLUSIONS Our findings suggest that alcohol drinking may be moderately associated with increased melanoma risk, although residual confounding and bias cannot be ruled out. Further research is needed to confirm these findings, clarify the role of the different alcohol sources, and investigate the interaction with known melanoma risk factors.
-
9.
Computed determination of the in vitro optimal chemocombinations of sphaeropsidin A with chemotherapeutic agents to combat melanomas.
Ingels, A, Dinhof, C, Garg, AD, Maddau, L, Masi, M, Evidente, A, Berger, W, Dejaegher, B, Mathieu, V
Cancer chemotherapy and pharmacology. 2017;(5):971-983
Abstract
PURPOSE Evasion to new treatments of advanced melanoma is still associated with a poor prognosis. Choosing the best combination of agents that can bypass resistance mechanisms remains a challenge. Sphaeropsidin A (Sph A) is a fungal bioactive secondary metabolite previously shown to force melanoma cells to undergo apoptosis via cell volume dysregulation. This work studied its in vitro combination with cytotoxic chemotherapeutics in a rational manner. METHODS Four melanoma cell lines harboring different sensitivity levels to pro-apoptotic stimuli were used to build a predictive response surface model allowing the determination of the optimal in vitro combinations of Sph A with two drugs, i.e., cisplatin or temozolomide, owing to a limited set of experimentations. RESULTS Testing 12 experimental combinations allowed us to build an accurate predictive model that considers the complexity of the drug interaction and determines the optimal combinations according to the endpoint chosen, i.e., the maximal cytotoxic effects. Therefore, combining 4 µM Sph A with 75 µM cisplatin concomitantly for 72 h improved its cytotoxic effects on melanoma cells in a synergistic manner. An optimal in vitro treatment schedule was also obtained for temozolomide. CONCLUSIONS The use of a response surface model offers the possibility of reducing the experiments while determining accurately the optimal combinations. We herein highlighted that combining the Na+/K+/2Cl- cotransporter and/or anion exchanger inhibitor Sph A with chemotherapeutic agents could improve the therapeutic benefits of conventional chemotherapies against advanced melanomas, particularly because Sph A exerts cytotoxic effects regardless of the genetic BRAF and NRAS status.
-
10.
Autoimmune diabetes induced by PD-1 inhibitor-retrospective analysis and pathogenesis: a case report and literature review.
Gauci, ML, Laly, P, Vidal-Trecan, T, Baroudjian, B, Gottlieb, J, Madjlessi-Ezra, N, Da Meda, L, Madelaine-Chambrin, I, Bagot, M, Basset-Seguin, N, et al
Cancer immunology, immunotherapy : CII. 2017;(11):1399-1410
Abstract
Anti-PD-1 antibody treatment is approved in advanced melanoma and provides median overall survival over 24 months. The main treatment-related side effects are immune-related adverse events, which include rash, pruritus, vitiligo, thyroiditis, diarrhoea, hepatitis and pneumonitis. We report a case of autoimmune diabetes related to nivolumab treatment. A 73-year-old man was treated in second line with nivolumab at 3 mg/kg every two weeks for metastatic melanoma. At 6 weeks of treatment, he displayed diabetic ketoacidosis. Nivolumab was withheld 3.5 weeks and insulin therapy was initiated, enabling a normalization of glycaemia and the disappearance of symptoms. Laboratory investigations demonstrated the presence of islet cell autoantibodies, while C-peptide was undetectable. Retrospective explorations on serum banked at week 0 and 3 months before the start of nivolumab, already showed the presence of autoantibodies, but normal insulin, C-peptide secretion and glycaemia. Partial response was obtained at month 3, and nivolumab was then resumed at the same dose. The clinical context and biological investigations before, at and after nivolumab initiation suggest the autoimmune origin of this diabetes, most likely induced by anti-PD-1 antibody in a predisposed patient. The role of PD-1/PD-L1 binding is well known in the pathogenesis of type 1 diabetes. Therefore, this rare side effect can be expected in a context of anti-PD-1 treatment. Glycaemia should be monitored during PD-1/PD-L1 blockade. The presence of autoantibodies before treatment could identify individuals at risk of developing diabetes, but systematic titration may not be relevant considering the rarity of this side effect.