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Article ; Online: Molecular Profiling and Novel Therapeutic Strategies for Mucosal Melanoma

Alice Indini / Fausto Roila / Francesco Grossi / Daniela Massi / Mario Mandalà

International Journal of Molecular Sciences, Vol 23, Iss 147, p

A Comprehensive Review

2022 Volume 147

Abstract: Mucosal melanoma is a rare and aggressive subtype of melanoma. Unlike its cutaneous counterpart, mucosal melanoma has only gained limited benefit from novel treatment approaches due to the lack of actionable driver mutations and poor response to ... ...

Abstract	Mucosal melanoma is a rare and aggressive subtype of melanoma. Unlike its cutaneous counterpart, mucosal melanoma has only gained limited benefit from novel treatment approaches due to the lack of actionable driver mutations and poor response to immunotherapy. Over the last years, whole-genome and exome sequencing techniques have led to increased knowledge on the molecular landscape of mucosal melanoma. Molecular studies have underlined noteworthy findings with potential therapeutic implications, including the presence of KIT mutations, which are potential targets of tyrosine kinase inhibitors currently in use in the clinic (imatinib), but also SF3B1 mutation, CDK4 amplifications, and CDKN2A gene deletions, which are presently under investigation in clinical trials. Recent results from a pooled analysis of patients with mucosal melanoma treated with immunotherapy have suggested that the combination of immune checkpoint inhibitors might improve survival outcomes in this subset of patients, as compared with single-agent immunotherapy. However, these results are not confirmed across different studies, and combo-immunotherapy correlates with a higher rate of adverse events. In this review, we describe the clinical, biological, and genetic features of mucosal melanoma. We also provide an update on the results of approved systemic treatment in this setting and overview the therapeutic strategies currently under investigation in clinical trials.
Keywords	melanoma ; mucosal ; immunotherapy ; targeted therapy ; c-kit ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Guarding net effects on landings and discards in Mediterranean trammel net fishery

Giacomo Sardo / Luca Vecchioni / Giacomo Milisenda / Fabio Falsone / Michele Luca Geraci / Daniela Massi / Pietro Rizzo / Danilo Scannella / Sergio Vitale

Frontiers in Marine Science, Vol

Case analysis of Egadi Islands Marine Protected Area (Central Mediterranean Sea, Italy)

2023 Volume 10

Abstract: Discards remain among the main negative impacts of fishing activities, and their reductions are strengthened by the European Common Fisheries Policy (European Regulation 1380/2013). Trammel net fisheries appear more sustainable compared with other ... ...

Abstract	Discards remain among the main negative impacts of fishing activities, and their reductions are strengthened by the European Common Fisheries Policy (European Regulation 1380/2013). Trammel net fisheries appear more sustainable compared with other fishing techniques, especially from an ecological viewpoint. Despite this, reports show that trammel net fisheries deliver discard quantities between 10% and 43% of the total catch biomass. To supplement existing information, this current work attempts to address the discard reduction using guarding net in the small-scale fisheries of Egadi Islands MPA (Western Sicily, Central Mediterranean Sea). To assess the reduction of unwanted catches, 48 experimental fishing trials were conducted within a 6-month period. The experimental fishing trial employed a trammel net made up of 20 panels alternated with two different net configurations. The control panels (CN) held a large outer (180 mm) and small inner (31.25 mm) meshes. The test panels (GN) with guarding net constituted a three-mesh-high (50-mm mesh size) net placed between trammel net panels and a lead line. A total of 3,310 individuals belonging to 106 taxa and nine phyla were caught. Crustaceans were the most abundant unwanted catches in the control panels, whereas bioconstructions occurred in the guarding net panels. The discard ratios of CN and GN panels were statistically different (t-value = –2.55; p< 0.05). The analysis of catch per unit effort showed higher catches of CN panels for both commercial and discard fractions (p< 0.05). Moreover, the guarding net panels caught the main discarded species at 20% lower compared with the control. The overall value of the catch at the CN panels (€ 3,366.90) was higher than the total income (€ 2,043.70) generated using the GN panels, which suggests a significant commercial loss of 40% (p< 0.05).
Keywords	multivariate analysis ; benthic assemblages ; sustainability ; unwanted catches ; discard ; by-catch reduction device ; Science ; Q ; General. Including nature conservation ; geographical distribution ; QH1-199.5
Subject code	333
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Spatial analysis of demersal food webs through integration of eDNA metabarcoding with fishing activities

Davide Cicala / Giulia Maiello / Fabio Fiorentino / Germana Garofalo / Daniela Massi / Alice Sbrana / Stefano Mariani / Simone D’Alessandro / Matteo Stefani / Lucie Perrodin / Tommaso Russo

Frontiers in Marine Science, Vol

2024 Volume 10

Abstract: The evaluation of the status of marine communities, and especially the monitoring of those heavily exploited by fisheries, is a key, challenging task in marine sciences. Fishing activities are a major source of disruption to marine food webs, both ... ...

Abstract	The evaluation of the status of marine communities, and especially the monitoring of those heavily exploited by fisheries, is a key, challenging task in marine sciences. Fishing activities are a major source of disruption to marine food webs, both directly, by selectively removing components at specific trophic levels (TL), and indirectly, by altering habitats and production cycles. Food web analysis can be very useful in the context of an Ecosystem Approach to Fisheries, but food web reconstructions demand large and expensive data sets, which are typically available only for a small fraction of marine ecosystems. Recently, new technologies have been developed to easily, quickly and cost-effectively collect environmental DNA (eDNA) during fishing activities. By generating large, multi-marker metabarcoding data from eDNA samples obtained from commercial trawlers, it is possible to produce exhaustive taxonomic inventories for the exploited ecosystems, which are suitable for food-web reconstructions. Here, we integrate and re-analyse the data of a recent study in which the α diversity was investigated using the eDNA opportunistically collected during fishing operations. Indeed, we collect highly resolved information on species feeding relationships to reconstruct the food webs at different sites in the Strait of Sicily (Mediterranean Sea) from eDNA and catch data. After observing that the trophic networks obtained from eDNA metabarcoding data are more consistent with the available knowledge, a set of food web indicators (species richness, number of links, direct connectance and generality) is computed and analysed to unravel differences in food webs structure through different areas (spatial variations). Species richness, number of links and generality (positively) and direct connectance (negatively) are correlated with increasing distance from the coast and fishing effort intensity. The combined effects of environmental gradients and fishing effort on food web structure at different study sites are then examined ...
Keywords	Food Webs Analysis (FWA) ; environmental DNA (eDNA) ; marine communities ; abiotic factors ; fishing pressure ; Mediterranean Sea ; Science ; Q ; General. Including nature conservation ; geographical distribution ; QH1-199.5
Subject code	333 ; 590
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Formalin safety in anatomic pathology workflow and integrated air monitoring systems for the formaldehyde occupational exposure assessment

Stefano Dugheri / Daniela Massi / Nicola Mucci / Nicola Berti / Giovanni Cappelli / Giulio Arcangeli

International Journal of Occupational Medicine and Environmental Health, Vol 34, Iss 3, Pp 319-

2021 Volume 338

Abstract: The potential carcinogenicity of formaldehyde (FA) has prompted increasing preventive measures in anatomic pathology (AP) laboratories and new strategies aimed at innovating airborne FA monitoring systems. This review provides an updated overview of the ... ...

Abstract	The potential carcinogenicity of formaldehyde (FA) has prompted increasing preventive measures in anatomic pathology (AP) laboratories and new strategies aimed at innovating airborne FA monitoring systems. This review provides an updated overview of the most recent improvements in preventive measures, safe practices, and exposure monitoring tools in the FA usage and handling. A computer-based search of scientific and non-scientific sources was performed on PubMed, Web of Science, Google and Google Patents databases, querying the main topics of real-time, in-continuous FA monitoring instruments for sale, and commercially available tools for improving preventive measures in formalin management. In order to simplify the sampling process and to choose a better analytic solution to FA assessment, the main characteristics of each FA monitoring instrument were described. The novel technical tools recently introduced on the global market, aimed at reducing FA emissions in AP laboratories, were summarized. This review is directed at anatomic pathologists to draw their attention to the rapidly growing field of safe formalin practices. A repeated exposure assessment is recommended to evaluate technical changes in air monitoring programs to keep FA emissions low, in compliance with the limit value; thus, evolved monitoring devices are needed. Int J Occup Med Environ Health. 2021;34(3):319–38
Keywords	formaldehyde ; mitigation ; formalin ; exposure monitoring ; anatomic pathology ; occupational exposure ; Medicine ; R
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Nofer Institute of Occupational Medicine
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Granulomatous Dermatitis and Systemic Disease

Alberto Corrà / Lavinia Quintarelli / Alice Verdelli / Francesca Portelli / Daniela Massi / Marzia Caproni

BioMed Research International, Vol

An Association to Consider

2020 Volume 2020

Abstract: Granuloma annulare (GA) and interstitial granulomatous dermatitis (IGD) are granulomatous dermatoses with variable clinical appearances. GA is associated with diabetes mellitus, metabolic syndrome, chronic infections, and malignancies, while two Japanese ...

Abstract	Granuloma annulare (GA) and interstitial granulomatous dermatitis (IGD) are granulomatous dermatoses with variable clinical appearances. GA is associated with diabetes mellitus, metabolic syndrome, chronic infections, and malignancies, while two Japanese reports described unusual cases of interstitial-type GA in setting of Sjogren syndrome. IGD was associated with rheumatoid arthritis, systemic lupus erythematosus, and autoantibodies. We report a case series of six patients with GA or IGD. Half of the patients were diagnosed with Sjogren syndrome, while all of them presented ANA positivity and the majority reported arthralgia. In many cases, GA showed interstitial-type histology, arising challenges in differential diagnosis with IGD. The overlap of clinical and histological features of GA and IGD can be explained considering them as a broad disease spectrum, including also the other forms of reactive granulomatous dermatitis. These conditions should be considered as an indicator of possible systemic disorders or other immunological dyscrasias, for which patients must be screened. Sjogren syndrome may be associated to GA also in Caucasians.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sweet Syndrome Following SARS-CoV2 Vaccination

Maria Efenesia Baffa / Roberto Maglie / Neri Giovannozzi / Francesca Montefusco / Stefano Senatore / Daniela Massi / Emiliano Antiga

Vaccines, Vol 9, Iss 1212, p

2021 Volume 1212

Abstract: Vaccines are today considered one of the most effective means against the Sars-CoV-2 pandemic. The BNT162b2 vaccine by Pfizer/BioNTech has been massively administered throughout the globe; since its approval, a wide spectrum of cutaneous reactions has ... ...

Abstract	Vaccines are today considered one of the most effective means against the Sars-CoV-2 pandemic. The BNT162b2 vaccine by Pfizer/BioNTech has been massively administered throughout the globe; since its approval, a wide spectrum of cutaneous reactions has been reported. Here we report the case of a 52-year-old Caucasian male who presented with an acute febrile eruption that arose 72 h after the first dose of the BNT162b2 vaccine. The clinicopathological findings were consistent with Sweet’s syndrome. The short latency time suggested a possible role of the vaccine in triggering Sweet’s syndrome in this case.
Keywords	Sweet’s syndrome ; mRNA vaccines ; neutrophilic dermatoses ; adverse event ; Medicine ; R
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Tumors carrying BRAF-mutations over-express NAMPT that is genetically amplified and possesses oncogenic properties

Valentina Audrito / Enrico Moiso / Filippo Ugolini / Vincenzo Gianluca Messana / Lorenzo Brandimarte / Ilaria Manfredonia / Simonetta Bianchi / Francesco De Logu / Romina Nassini / Anna Szumera-Ciećkiewicz / Daniela Taverna / Daniela Massi / Silvia Deaglio

Journal of Translational Medicine, Vol 20, Iss 1, Pp 1-

2022 Volume 13

Abstract: Abstract Background Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis, is up-regulated in several cancers, including metastatic melanoma (MM). The BRAF oncogene is mutated in ... ...

Abstract	Abstract Background Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis, is up-regulated in several cancers, including metastatic melanoma (MM). The BRAF oncogene is mutated in different cancer types, among which MM and thyroid carcinoma (THCA) are prominent. Drugs targeting mutant BRAF are effective, especially in MM patients, even though resistance rapidly develops. Previous data have linked NAMPT over-expression to the acquisition of BRAF resistance, paving the way for therapeutic strategies targeting the two pathways. Methods Exploiting the TCGA database and a collection of MM and THCA tissue microarrays we studied the association between BRAF mutations and NAMPT expression. BRAF wild-type (wt) cell lines were genetically engineered to over-express the BRAF V600E construct to demonstrate a direct relationship between over-activation of the BRAF pathway and NAMPT expression. Responses of different cell line models to NAMPT (i)nhibitors were studied using dose–response proliferation assays. Analysis of NAMPT copy number variation was performed in the TCGA dataset. Lastly, growth and colony forming assays were used to study the tumorigenic functions of NAMPT itself. Results The first finding of this work is that tumor samples carrying BRAF-mutations over-express NAMPT, as demonstrated by analyzing the TCGA dataset, and MM and THC tissue microarrays. Importantly, BRAF wt MM and THCA cell lines modified to over-express the BRAF V600E construct up-regulated NAMPT, confirming a transcriptional regulation of NAMPT following BRAF oncogenic signaling activation. Treatment of BRAF-mutated cell lines with two different NAMPTi was followed by significant reduction of tumor growth, indicating NAMPT addiction in these cells. Lastly, we found that several tumors over-expressing the enzyme, display NAMPT gene amplification. Over-expression of NAMPT in BRAF wt MM cell line and in fibroblasts resulted in increased growth capacity, arguing in favor of ...
Keywords	NAMPT ; Oncogene ; Transformation ; BRAF oncogenic signaling ; MAPK ; NAMPT inhibitors ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients

Francesco De De Logu / Francesca Galli / Romina Nassini / Filippo Ugolini / Sara Simi / Mara Cossa / Clelia Miracco Andrea Miracco / Vincenzo De De Giorgi / Eliana Rulli / Antonio Cossu / Daniela Massi / Mario Mandalà

Cells, Vol 10, Iss 422, p

2021 Volume 422

Abstract: Background: the prognostic significance of tumor infiltrating lymphocytes (TILs) in intermediate/thick primary cutaneous melanoma (PCM) remains controversial, partially because conventional evaluation is not reliable, due to inter-observer variability ... ...

Abstract	Background: the prognostic significance of tumor infiltrating lymphocytes (TILs) in intermediate/thick primary cutaneous melanoma (PCM) remains controversial, partially because conventional evaluation is not reliable, due to inter-observer variability and diverse scoring methods. We aimed to assess the prognostic impact of the density and spatial distribution of immune cells in early stage intermediate/thick PCM. Materials and Methods: digital image acquisition and quantitative analysis of tissue immune biomarkers (CD3, CD4, CD8, CD68, PD-L1, CD163, FOX-P3, and PD-1) was carried out in a training cohort, which included patients with primary PCM ³ 2 mm diagnosed, treated, and followed-up prospectively in three Italian centers. Results were validated in an independent Italian cohort. Results: in the training cohort, 100 Stage II–III melanoma patients were valuable. At multivariable analysis, a longer disease free survival (DFS) was statistically associated with higher levels of CD4 + intratumoral T-cells (aHR [100 cell/mm 2 increase] 0.98, 95%CI 0.95–1.00, p = 0.041) and CD163 + inner peritumoral (aHR [high vs. low] 0.56, 95%CI 0.32–0.99, p = 0.047). A statistically significant longer DFS (aHR [high-high vs. low-low] 0.52, 95%CI 0.28–0.99, p = 0.047) and overall survival (OS) (aHR [high-high vs. low-low] 0.39, 95%CI 0.18–0.85, p = 0.018) was found in patients with a high density of both intratumoral CD8 + T-cells and CD68 + macrophages as compared to those with low density of both intratumoral CD8 + T-cells and CD68 + macrophages. Consistently, in the validation cohort, patients with high density of both intratumoral CD8 + and CD3 + T-cells were associated to a statistically better DFS (aHR[high-high vs. low-low] 0.24, 95%CI 0.10–0.56, p < 0.001) and those with high density of both intratumoral CD8 + and CD68 + were associated to a statistically longer OS (aHR[high-high vs. low-low] 0.28, 95%CI 0.09–0.86, p = 0.025). Conclusion: our findings suggest that a specific preexisting profile of T cells and macrophages ...
Keywords	melanoma ; digital pathology ; tumor infiltrating lymphocytes ; Biology (General) ; QH301-705.5
Subject code	333
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The TRPA1 Channel Amplifies the Oxidative Stress Signal in Melanoma

Francesco De Logu / Daniel Souza Monteiro de Araujo / Filippo Ugolini / Luigi Francesco Iannone / Margherita Vannucchi / Francesca Portelli / Lorenzo Landini / Mustafa Titiz / Vincenzo De Giorgi / Pierangelo Geppetti / Daniela Massi / Romina Nassini

Cells, Vol 10, Iss 3131, p

2021 Volume 3131

Abstract: Macrophages (MΦs) and reactive oxygen species (ROS) are implicated in carcinogenesis. The oxidative stress sensor, transient receptor potential ankyrin 1 (TRPA1), activated by ROS, appears to contribute to lung and breast cancer progression. Although ... ...

Abstract	Macrophages (MΦs) and reactive oxygen species (ROS) are implicated in carcinogenesis. The oxidative stress sensor, transient receptor potential ankyrin 1 (TRPA1), activated by ROS, appears to contribute to lung and breast cancer progression. Although TRPA1 expression has been reported in melanoma cell lines, and oxidative stress has been associated with melanocytic transformation, their role in melanoma remains poorly known. Here, we localized MΦs, the final end-product of oxidative stress, 4-hydroxynonenal (4-HNE), and TRPA1 in tissue samples of human common dermal melanocytic nevi, dysplastic nevi, and thin (pT1) and thick (pT4) cutaneous melanomas. The number (amount) of intratumoral and peritumoral M2 MΦs and 4-HNE staining progressively increased with tumor severity, while TRPA1 expression was similar in all samples. Hydrogen peroxide (H 2 O 2 ) evoked a TRPA1-dependent calcium response in two distinct melanoma cell lines (SK-MEL-28 and WM266-4). Furthermore, H 2 O 2 induced a TRPA1-dependent H 2 O 2 release that was prevented by the TRPA1 antagonist, A967079, or Trpa1 gene silencing (siRNA). ROS release from infiltrating M2 MΦs may target TRPA1-expressing melanoma cells to amplify the oxidative stress signal that affects tumor cell survival and proliferation.
Keywords	oxidative stress ; melanoma ; macrophages ; TRPA1 ; image analysis ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Droplet digital PCR (ddPCR) vs quantitative real-time PCR (qPCR) approach for detection and quantification of Merkel cell polyomavirus (MCPyV) DNA in formalin fixed paraffin embedded (FFPE) cutaneous biopsies

Arvia, Rosaria / Mauro Sollai / Federica Pierucci / Carmelo Urso / Daniela Massi / Krystyna Zakrzewska

Journal of virological methods. 2017,

2017

Abstract: Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma and high viral load in the skin was proposed as a risk factor for the occurrence of this tumour. MCPyV DNA was detected, with lower frequency, in different skin cancers but since ... ...

Abstract	Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma and high viral load in the skin was proposed as a risk factor for the occurrence of this tumour. MCPyV DNA was detected, with lower frequency, in different skin cancers but since the viral load was usually low, the real prevalence of viral DNA could be underestimated.To evaluate the performance of two assays (qPCR and ddPCR) for MCPyV detection and quantification in formalin fixed paraffin embedded (FFPE) tissue samples.Both assays were designed to simultaneous detection and quantification of both MCPyV as well as house-keeping DNA in clinical samples. The performance of MCPyV quantification was investigated using serial dilutions of cloned target DNA. We also evaluated the applicability of both tests for the analysis of 76 FFPE cutaneous biopsies.The two approaches resulted equivalent with regard to the reproducibility and repeatability and showed a high degree of linearity in the dynamic range tested in the present study. Moreover, qPCR was able to quantify â¥105 copies per reaction, while the upper limit of ddPCR was 104 copies. There was not significant difference between viral load measured by the two methods The detection limit of both tests was 0,15 copies per reaction, however, the number of positive samples obtained by ddPCR was higher than that obtained by qPCR (45% and 37% respectively).The ddPCR represents a better method for detection of MCPyV in FFPE biopsies mostly these containing low copies number of viral genome.
Keywords	DNA ; Polyomavirus ; biopsy ; formalin ; genome ; quantitative polymerase chain reaction ; risk factors ; skin neoplasms ; viral load
Language	English
Size	p. .
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2017.04.003
Database	NAL-Catalogue (AGRICOLA)

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