Melanoma epidemiology, prognosis and trends in Latvia

Background Melanoma incidence and mortality rates are increasing worldwide within the white population. Clinical and histological factors have been usually used for the prognosis and assessment of the risk for melanoma. Objectives The aim of the study was to describe the clinical and histopathological features of the cutaneous melanoma (CM) in the Latvian population, to test the association between melanoma features and patient survival, and to assess the time trends for melanoma incidence. Methods We undertook a descriptive, retrospective analysis of archive data of 984 melanoma patients treated at the largest oncological hospital of Latvia, Riga East University Hospital Latvian Oncology Centre (LOC), between 1998 and 2008. Cox proportional hazards model was used to analyse patient survival and autoregressive models were applied to detect trends in melanoma incidence over time for various categories of melanoma. Results The study showed a significant ascending trend in melanoma incidence in Latvia during the time period from 1998 to 2008 (ß = 1.83, 95% CI = 1.15-2.91, P = 0.011). Nodular melanoma was the most common tumour subtype with a frequency of 39.2%. Ulceration was present in 45.2% of melanomas. The mean Breslow thickness was 6.0 mm (6.8 mm) and no significant decline in median Breslow thickness was observed during the study period (P = 0.609). A better overall prognosis was detected for females in comparison with males (HR = 1.49; 95% CI = 1.22-1.81; P < 0.001). Conclusions There is a steady increase in melanoma incidence in Latvia with the majority of melanomas diagnosed at late stages with poor prognosis for survival.publishersversionPeer reviewe

POLARIZED ACTIVATION OF HUMAN PERIPHERAL BLOOD PHAGOCYTES BY BACTERIOPHAGE–DERIVED DOUBLE-STRANDED RNA (LARIFAN) IN VITRO

Aim. This study aimed to examine the effect of Larifan on metabolic characteristics of human blood monocytes and granulocytes in vitro. Methods. Four healthy adult men aged 21-26 years were recruited to participate in the study as blood donors. The metabolic profile of human blood monocytes and granulocytes was evaluated by phagocytic activity, reactive oxygen species production, nitric oxide generation, and arginase activity. Phagocytosis of FITC-labeled inactivated Staphylococcus aureus and reactive oxygen species generation were estimated by flow cytometry. Arginase activity was assessed in cell lysates, and nitric oxide generation in supernatants was examined using the Griess reaction. Results. Phagocytic index and reactive oxygen species generation were found to be lower in both human blood monocytes and granulocytes treated with Larifan. The drug caused a dose-dependent increase in nitric oxide production, as well as a decrease in the arginase activity of blood monocytes. Conclusions. Our results indicate the ability of Larifan to reinforce the antiviral properties of resting phagocytes along with containment of oxidative stress development

The effect of intranasally administered TLR3 agonist larifan on metabolic profile of microglial cells in rat with C6 glioma

Glioma-associated microglia/macrophages (GAM) represent an attractive therapeutic target for the development of the alternative methodology in the treatment of gliomas. This study was aimed to investigate the effect of intranasally administered TLR3 agonist Larifan on microglial cell metabolic profile in rats with C6 glioma. Our results demonstrate progressive generation microglial cell population with immunosuppressive and pro-inflammatory properties in C6 glioma-bearing brain. Intranasally delivered TLR3 agonist is capable to abrogate the creation of this pro-tumoral immune infiltrates, probably, through the effect on myeloid-derived suppressor cells, and can be considered as a promising agent for glioma therapy aimed the GAM re-education

Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families

<p>Abstract</p> <p>Background</p> <p>Two high-risk genes have been implicated in the development of CM (cutaneous melanoma). Germline mutations of the CDKN2A gene are found in < 25% of melanoma-prone families and there are only seven families with mutation of the <it>CDK4 </it>gene reported to date. Beside those high penetrance genes, certain allelic variants of the <it>MC1R </it>gene modify the risk of developing the disease.</p> <p>The aims of our study were: to determine the prevalence of germline <it>CDKN2A </it>mutations and variants in members of families with familial CM and in patients with multiple primary CM; to search for possible <it>CDK4 </it>mutations, and to determine the frequency of variations in the <it>MC1R </it>gene.</p> <p>Methods</p> <p>From January 2001 until January 2007, 64 individuals were included in the study. The group included 28 patients and 7 healthy relatives belonging to 25 families, 26 patients with multiple primary tumors and 3 children with CM. Additionally 54 healthy individuals were included as a control group. Mutations and variants of the melanoma susceptibility genes were identified by direct sequencing.</p> <p>Results</p> <p>Seven families with CDKN2A mutations were discovered (7/25 or 28.0%). The L94Q mutation found in one family had not been previously reported in other populations. The D84N variant, with possible biological impact, was discovered in the case of patient without family history but with multiple primary CM. Only one mutation carrier was found in the control group. Further analysis revealed that c.540C>T heterozygous carriers were more common in the group of CM patients and their healthy relatives (11/64 vs. 2/54). One p14ARF variant was discovered in the control group and no mutations of the <it>CDK4 </it>gene were found.</p> <p>Most frequently found variants of the <it>MC1R </it>gene were T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the group of patients and their relatives than in the group of controls, but the difference was statistically insignificant.</p> <p>Conclusion</p> <p>The present study has shown high prevalence of p16INK4A mutations in Slovenian population of familial melanoma patients (37%) and an absence of p14ARF or <it>CDK4 </it>mutations.</p

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT

Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved. Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics. Results: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P &lt; .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance. Conclusion: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling

Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families.

Funder: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; doi: http://dx.doi.org/10.13039/501100002322Funder: Radiumhemmets Forskningsfonder; doi: http://dx.doi.org/10.13039/501100007232Funder: Swedish Cancer SocietyFunder: Lunds Universitet Paulsson TrustFunder: CIBER de Enfermedades Raras of the Instituto de Salud Carlos IIIFunder: European Regional Development Fund; doi: http://dx.doi.org/10.13039/501100008530Funder: DiagnopticsFunder: CERCA Programme Generalitat de CatalunyaFunder: Esther Koplowitz Center, Barcelona, SpainFunder: Comision Honoraria de Lucha Contra el Cancer, CSIC, Fundacion Manuel Perez, Montevideo, UruguayBACKGROUND: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. METHODS: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. RESULTS: A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. CONCLUSIONS: Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families

Telomere length and survival in primary cutaneous melanoma patients (vol 8, 10947, 2018)

Dermatology-oncolog

Association of HERV-K and LINE-1 hypomethylation with reduced disease-free survival in melanoma patients

Aim: To evaluate CpG methylation of long interspersed nuclear elements 1 (LINE-1) and human endogenous retrovirus K (HERV-K) retroelements as potential prognostic biomarkers in cutaneous melanoma. Materials & methods: Methylation of HERV-K and LINE-1 retroelements was assessed in resected melanoma tissues from 82 patients ranging in age from 14 to 88 years. In addition, nevi from eight patients were included for comparison with nonmalignant melanocytic lesions. Results: Methylation levels were lower in melanomas than in nevi. HERV-K and LINE-1 methylation were decreased in melanoma patients with clinical parameters associated with adverse prognosis, while they were independent of age and gender. Hypomethylation of HERV-K (but not LINE-1) was an independent predictor of reduced disease-free survival. Conclusion: HERV-K hypomethylation can be a potential independent biomarker of melanoma recurrence.Dermatology-oncolog