Updated Field Synopsis and Systematic Meta-Analyses of Genetic Association Studies in Cutaneous Melanoma: The MelGene Database

We updated a field synopsis of genetic associations of cutaneous melanoma (CM) by systematically retrieving and combining data from all studies in the field published as of August 31, 2013. Data were available from 197 studies, which included 83,343 CM cases and 187,809 controls and reported on 1,126 polymorphisms in 289 different genes. Random-effects meta-analyses of 81 eligible polymorphisms evaluated in >4 data sets confirmed 20 single-nucleotide polymorphisms across 10 loci (TYR, AFG3L1P, CDK10, MYH7B, SLC45A2, MTAP, ATM, CLPTM1L, FTO, and CASP8) that have previously been published with genome-wide significant evidence for association (P<5 × 10−8) with CM risk, with certain variants possibly functioning as proxies of already tagged genes. Four other loci (MITF, CCND1, MX2, and PLA2G6) were also significantly associated with 5 × 10−8<P<1 × 10−3. In supplementary meta-analyses derived from genome-wide association studies, one additional locus located 11 kb upstream of ARNT (chromosome 1q21) showed genome-wide statistical significance with CM. Our approach serves as a useful model in analyzing and integrating the reported germline alterations involved in CM

Occurrence of Black Aspergilli and Ochratoxin A on Grapes in Italy

Ochratoxin A (OTA) in wine is linked to contamination by several Aspergillus species. In 2003–2007, grape samples collected in Italy were surveyed for the presence of OTA and OTA-producing fungi. A. niger aggregate was the prevalent species. A. carbonarius, which is considered the main source of OTA in grapes, was mostly found in Southern Italy. The year and the environment had an important influence on the development of the black Aspergillus populations. Testing with ELISA showed OTA to be present in about 30% of the samples. Samples from Southern Italy showed the highest occurrence (45%) and also the highest OTA concentration, sometimes higher than 2 μg/L. The values decreased progressively the further North the samples were taken

Photodiagnosis and photodynamic therapy of HPV infections of skin and mucocutaneous areas

Condylomata acuminata consist the most common sexually transmitted viral disease. A big percentage of the sexually active population is infected by one or more Human Papilloma Virus (HPV) types. However, the number of patients presenting with clinically overt lesions represent only the tip of the iceberg, since most genital tract HPV infections are subclinical or latent. Consequently, clinical examination underestimates the extent of HPV infection, whereas in vitro diagnostic methods are expensive and time consuming. HPV 16, 18 and other HPV types have been detected frequently in carcinomas of the cervix, vulva, penis and anus. Although condylomata acuminata represent a great epidemiological problem, there is still no gold-standard therapy, since all treatment modalities have moderate response rates and relatively high recurrence rates. In addition, all therapeutic modalities aim to the destruction of clinically overt disease, since eradication of HPV is impossible. The aim of this study was the in vivo detection and staging of HPV infection of anogenital area by quantitative assessment of the acetic acid-induced temporal and spatial alterations in the light-scattering properties of HPV-infected skin. For this reason an imaging system has been employed, which performs time-lapse imaging and enables the calculation and display of the kinetics of the provoked alterations in any point within the examined area. Lesions of anogenital area with clinical diagnosis of condylomata acuminata were studied. The evaluation of acetic acid-tissue interaction kinetics revealed quantitative parameters, containing information about the magnitude and duration of the provoked alterations. The histology evaluation and polymerase chain reaction performed, showed that the method contains specific diagnostic information, since it enables the differentiation between subclinical lesions, clinical condylomata acuminata and squamous cell carcinomas developing on condylomata. It also allows the exact localization of lesions and delineates their borders. Photodynamic therapy efficacy in condylomata acuminata after topical application of δ-aminolevulinic acid (ALA) was also assessed. ALA-induced protoporphyrin IX (PpIX) fluorescence kinetics were studied, in order to select for PDT suitable lesions that show selective accumulation of PpIX. The optimal time of illumination was determined, so as to improve PDT efficacy by individualizing the procedure. The overall cure rate was 72.9% 12 months after treatment, indicating that ALA-PDT is a potential effective treatment for condylomata acuminata.Τα οξυτενή κονδυλώματα αποτελούν τη συχνότερη ιογενή σεξουαλικώς μεταδιδόμενη νόσο. Ο αριθμός των ασθενών με κλινικά ορατή νόσο αποτελεί ένα μικρό μόνο ποσοστό των ατόμων με υποκλινική και λανθάνουσα μόλυνση από τον ιό του θηλώματος του ανθρώπου (Human Papilloma Virus-HPV), καθώς μεγάλο μέρος του σεξουαλικά ενεργού πληθυσμού είναι μολυσμένο από ένα ή περισσότερους HPV τύπους. Κατά συνέπεια, η φυσική εξέταση υποεκτιμά την έκταση της μόλυνσης από HPV, ενώ οι in vitro διαγνωστικές μέθοδοι είναι δαπανηρές και χρονοβόρες. Οι HPV 16, 18 καθώς και άλλοι τύποι του ιού έχουν ανιχνευθεί σε μεγάλο ποσοστό στον καρκίνο του τραχήλου της μήτρας, του αιδοίου, του πέους και του πρωκτού. Παρότι τα οξυτενή κονδυλώματα αποτελούν μεγάλο επιδημιολογικό πρόβλημα, δεν υπάρχει έως σήμερα κοινά αποδεκτή θεραπεία εκλογής, καθώς οι συμβατικές θεραπείες έχουν μέτρια ποσοστά ανταπόκρισης και σχετικά υψηλά ποσοστά υποτροπών. Επιπλέον, όλες οι θεραπευτικές μέθοδοι στοχεύουν στην καταστροφή των ορατών βλαβών καθώς η εκρίζωση του ιού είναι αδύνατη. Στην παρούσα έρευνα έγινε προσπάθεια in vivo ανίχνευσης και σταδιοποίησης της HPV μόλυνσης της περιγεννητικής και περιπρωκτικής περιοχής, μελετώντας τις χωρικές και χρονικές μεταβολές που προκαλεί το οξεΐκό οξύ στις ιδιότητες σκέδασης φωτός του προσβεβλημένου από HPV ιστού. Για την καταγραφή και εκτίμηση αυτών των μεταβολών χρησιμοποιήθηκε ένα πρωτότυπο σύστημα πολυφασματικής απεικόνισης. Μελετήθηκαν δερματικές βλάβες ασθενών με κλινική εικόνα οξυτενών κονδυλωμάτων της περιγεννητικής και περιπρωκτικής χώρας. Η αξιολόγησης της κινητικής της αλληλεπίδρασης οξεΐκού οξέος-ιστού ανέδειξε ποσοτικές παραμέτρους, που περιλαμβάνουν πληροφορίες τόσο για το μέγεθος όσο και για τη διάρκεια των επαγόμενων μεταβολών. Η εκτίμηση των βλαβών με ιστολογική εξέταση και την τεχνική της αλυσιδωτής αντίδρασης πολυμεράσης (PCR), επιβεβαίωσε ότι η μέθοδος περιέχει ειδική διαγνωστική πληροφορία, καθώς κάνει δυνατή τη διάκριση μεταξύ υποκλινικών βλαβών, κλινικών κονδυλωμάτων και ακανθοκυτταρικών καρκινωμάτων που αναπτύσσονται σε έδαφος HPV μόλυνσης. Επίσης επιτρέπει την ακριβή εντόπιση και περιγραφή των ορίων των βλαβών. Επίσης εκτιμήθηκε η αποτελεσματικότητα της φωτοδυναμικής θεραπείας οξυτενών κονδυλωμάτων με δ-αμινολεβουλινικό οξύ (ALA). Προηγήθηκε μελέτη της κινητικής του φθορισμού της πρωτοπορφυρίνης ΙΧ (PpIX) μετά από επάλειψη των βλαβών με ALA, προκειμένου να επιλεγούν για φωτοδυναμική θεραπεία όσες παρουσίασαν εκλεκτική συγκέντρωση του φωτοευαισθητοποιητή. Επιπλέον υπολογίστηκε ο ιδανικός χρόνος έναρξης της ακτινοβόλησης κατά τη διάρκεια της φωτοδυναμικής θεραπείας ώστε να εξατομικευτεί και να βελτιστοποιηθεί η μέθοδος. Το ποσοστό ίασης των βλαβών μετά από παρακολούθηση ενός έτους ήταν 72,9%, αποδεικνύοντας ότι η φωτοδυναμική θεραπεία με ALA αποτελεί μία υποσχόμενη μέθοδο στην αντιμετώπιση των οξυτενών κονδυλωμάτων

Germline CDKN2A mutations among Greek patients with early-onset and multiple primary cutaneous melanoma

The genetic basis of melanoma susceptibility among Greek patients is uncharacterized. From 107 consecutive cutaneous melanoma patients, we analyzed the CDKN2A and CDK4 loci among 18 early-onset (&lt;= 40 years) and two multiplex melanoma cases. Overall, we found three CDKN2A mutations (3/20; 15%), including one novel nonsense mutation (Trp110Stop) and two Arg24Pro missense alterations. There were no mutations in ARF or CDK4. CDKN2A mutations are not uncommon among Greek melanoma patients considering that none of the mutation carriers reported a family history of melanoma

A Comprehensive Analysis of Cutaneous Melanoma Patients in Greece Based on Multi-Omic Data

Cutaneous melanoma (CM) is the most aggressive type of skin cancer, and it is characterised by high mutational load and heterogeneity. In this study, we aimed to analyse the genomic and transcriptomic profile of primary melanomas from forty-six Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from Greek patients. Molecular analysis for both germline and somatic variations was performed in genomic DNA from peripheral blood and melanoma samples, respectively, exploiting whole exome and targeted sequencing, and transcriptomic analysis. Detailed clinicopathological data were also included in our analyses and previously reported associations with specific mutations were recognised. Most analysed samples (43/46) were found to harbour at least one clinically actionable somatic variant. A subset of samples was profiled at the transcriptomic level, and it was shown that specific melanoma phenotypic states could be inferred from bulk RNA isolated from FFPE primary melanoma tissue. Integrative bioinformatics analyses, including variant prioritisation, differential gene expression analysis, and functional and gene set enrichment analysis by group and per sample, were conducted and molecular circuits that are implicated in melanoma cell programmes were highlighted. Integration of mutational and transcriptomic data in CM characterisation could shed light on genes and pathways that support the maintenance of phenotypic states encrypted into heterogeneous primary tumours

A Comprehensive Analysis of Cutaneous Melanoma Patients in Greece Based on Multi-Omic Data

Cutaneous melanoma (CM) is the most aggressive type of skin cancer, and it is characterised by high mutational load and heterogeneity. In this study, we aimed to analyse the genomic and transcriptomic profile of primary melanomas from forty-six Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from Greek patients. Molecular analysis for both germline and somatic variations was performed in genomic DNA from peripheral blood and melanoma samples, respectively, exploiting whole exome and targeted sequencing, and transcriptomic analysis. Detailed clinicopathological data were also included in our analyses and previously reported associations with specific mutations were recognised. Most analysed samples (43/46) were found to harbour at least one clinically actionable somatic variant. A subset of samples was profiled at the transcriptomic level, and it was shown that specific melanoma phenotypic states could be inferred from bulk RNA isolated from FFPE primary melanoma tissue. Integrative bioinformatics analyses, including variant prioritisation, differential gene expression analysis, and functional and gene set enrichment analysis by group and per sample, were conducted and molecular circuits that are implicated in melanoma cell programmes were highlighted. Integration of mutational and transcriptomic data in CM characterisation could shed light on genes and pathways that support the maintenance of phenotypic states encrypted into heterogeneous primary tumours

Seasonal pattern of the diagnosis of cutaneous melanoma: a hospital-based study in a Mediterranean country

Background Several investigators have described a seasonal variation in the diagnosis of cutaneous melanoma. Limited data exist on the seasonality of melanoma diagnosis in Southern European countries. Patients and methods The seasonal pattern of diagnosis was analyzed in 404 Greek patients diagnosed with cutaneous melanoma (CM) between 1996 and 2004. A summer-to-winter ratio was determined overall and in relation to gender, age, anatomic site, histopathologic type, and tumor thickness. Results The summer-to-winter ratio was 1.53 for all patients ( 95% Cl [confidence interval]: 1.15-2.02) with a ratio of 1.83 for women (95% Cl: 1.20-2.78) and 1.28 for men ( 95% Cl: 0.87-1.88). A seasonal pattern of melanoma diagnosis was observed for patients younger than 50 years of age (1.70, 95% Cl: 1.05-2.74) and between 50 and 69 years ( 1.64, 95% Cl: 1.05-2.56), for melanoma located on the upper or lower extremities (2.50, 95% Cl: 1.12-5.56 and 2.23, 95% Cl: 1.19-4.18, respectively), for superficial spreading and nodular melanomas (1.73, 95% Cl: 1.12-2.69 and 1.52 95% Cl: 0.96-2.41) and for melanomas with a tumor thickness of 1-2 mm (1.69, 95% Cl: 0.91-3.12) and &gt; 4 mm (2.13, 95% Cl: 1.04-4.35). Conclusions No major differences were seen in the seasonal distribution of CM diagnosis in a Mediterranean population compared to previously reported results. A better ascertainment of the skin during the summer and an increased awareness due to the melanoma screening campaigns are the more likely reasons for the seasonality of melanoma diagnosis in Greece

Proliferative and chondrogenic potential of mesenchymal stromal cells from pluripotent and bone marrow cells

Introduction. Mesenchymal stromal cells (MSCs) can be derived from a wide range of fetal and adult sources including pluripotent stem cells (PSCs). The properties of PSC-derived MSCs need to be fully characterized, in order to evaluate the feasibility of their use in clinical applications. PSC-MSC proliferation and differentiation potential in comparison with bone marrow (BM)-MSCs is still under investigation. The objective of this study was to determine the proliferative and chondrogenic capabilities of both human induced pluripotent stem cell (hiPSC-) and embryonic stem cell (hESC-) derived MSCs, by comparing them with BMMSCs. Methods. MSCs were derived from two hiPSC lines (hiPSC-MSCs), the well characterized Hues9 hESC line (hESC-MSCs) and BM from two healthy donors (BMMSCs). Proliferation potential was investigated using appropriate culture conditions, with serial passaging, until cells entered into senescence. Differentiation potential to cartilage was examined after in vitro chondrogenic culture conditions. Results. BM-MSCs revealed a fold expansion of 1.18x105 and 2.3x105 while the two hiPSC-MSC lines and hESC-MSC showed 5.88x1010, 3.49x108 and 2.88x108, respectively. Under chondrogenic conditions, all MSC lines showed a degree of chondrogenesis. However, when we examined the formed chondrocyte micromasses by histological analysis of the cartilage morphology and immunohistochemistry for the chondrocyte specific markers Sox9 and Collagen II, we observed that PSC-derived MSC lines had formed pink rather than hyaline cartilage, in contrast to BM-MSCs. Conclusion. In conclusion, MSCs derived from both hESCs and hiPSCs had superior proliferative capacity compared to BM-MSCs, but they were inefficient in their ability to form hyaline cartilag

Topical formulation containing peptides and vitamin C in ampoules improves skin aging signs: Results of a large, international, observational study

Introduction Peptide-C ampoules (PC) contain peptides, 10% of vitamin C, hyaluronic acid, and Vichy volcanic mineralizing water. Aims To assess the effectiveness and tolerability of PC. Patients and Methods An observational study conducted in 9 countries in women &gt;= 30 years old with signs of facial skin aging (grade &gt;0 for forehead and/or crow’s feet wrinkles and bothered by skin quality). Investigator assessments and subject questionnaires were performed at initial visit and Day 30 after application of PC twice daily for 28 days. Tolerance was assessed throughout the study. Results Effectiveness and safety were analyzed in 1382 and 1742 subjects, respectively. Most subjects (mean age 48.5 +/- 8.6 years) had skin phototype II or III (91.7%) and dry or combination skin (63.9%). PC was used as a standalone care or prior to a planned procedure (70%), or after a procedure (30%). Between baseline and Day 30, 63% and 64% of all subjects (N = 1360) had an improvement in forehead wrinkles and crow’s feet wrinkles, respectively. Skin hydration improved in 67.3% of subjects. According to investigator and subject assessments, skin quality, skin radiance, skin aging signs, wrinkles, complexion, and skin pores significantly improved by Day 30. Similar results were observed for subgroup analyses when PC was used as standalone skin care or after a procedure. Tolerance of PC was rated as good to very good by 97.7% of subjects. Conclusions Peptide-C ampoules is effective in reducing visible signs of skin aging, and well tolerated, when used alone or as an adjunct to anti-aging procedures

Updated Field Synopsis and Systematic Meta-Analyses of Genetic Association Studies in Cutaneous Melanoma: The MelGene Database

We updated a field synopsis of genetic associations of cutaneous melanoma (CM) by systematically retrieving and combining data from all studies in the field published as of August 31, 2013. Data were available from 197 studies, which included 83,343 CM cases and 187,809 controls and reported on 1,126 polymorphisms in 289 different genes. Random-effects meta-analyses of 81 eligible polymorphisms evaluated in &gt;4 data sets confirmed 20 single-nucleotide polymorphisms across 10 loci (TYR, AFG3L1P, CDK10, MYH7B, SLC45A2, MTAP, ATM, CLPTM1L, FTO, and CASP8) that have previously been published with genome-wide significant evidence for association (P&lt;5 x 10(-8)) with CM risk, with certain variants possibly functioning as proxies of already tagged genes. Four other loci (MITF, CCND1, MX2, and PLA2G6) were also significantly associated with 5 x 10-8 &lt;P&lt;1 x 10(-3). In supplementary meta-analyses derived from genome-wide association studies, one additional locus located 11 kb upstream of ARNT (chromosome 1q21) showed genome-wide statistical significance with CM. Our approach serves as a useful model in analyzing and integrating the reported germline alterations involved in CM