Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients' overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis

Concern about the spread of the invader seaweed Caulerpa taxifolia var. distichophylla (Chlorophyta: Caulerpales) towards the West Mediterranean

The new Australian alien seaweed Caulerpa taxifolia var. distichophylla, after being established along the Turkish Mediterranean coast in 2006, was recorded in Southern Sicily in 2007. Since then local fishermen claimed support to counteract the effects of entanglement of large amounts of the alien strain wrack in their trammel nets, causing the gear to become ineffective. The further northward and westward spread of the new alien strain is supposed to be limited by winter temperature. We present novel data confirming that the new alien strain is fully naturalized in Central Mediterranean and is expanding its range beyond such limit (i.e. the 15°C February isotherm), thus becoming potentially able to colonize the western basin. By means of a preliminary estimation of effects on native polychaete assemblages, and considering some peculiarities of Sicily (mostly linked to its geographical position in the Mediterranean Sea), the risk linked to the increasing range of distribution of the invasive algae is highlighted

Reducing the data-deficiency of threatened European habitats: Spatial variation of sabellariid worm reefs and associated fauna in the Sicily Channel, Mediterranean Sea

Biogenic reefs, such as those produced by tube-dwelling polychaetes of the genus Sabellaria, are valuable marine habitats which are a focus of protection according to European legislation. The achievement of this goal is potentially hindered by the lack of essential empirical data, especially in the Mediterranean Sea. This study addresses some of the current knowledge gaps by quantifying and comparing multi-scale patterns of abundance and distribution of two habitat-forming species (Sabellaria alveolata and S. spinulosa) and their associated fauna along 190 km of coast on the Italian side of the Sicily Channel. While the abundance of the two sabellariids and the total number of associated taxa did not differ at any of the examined scales (from tens of centimetres to tens-100 of kilometres), the structure (composition in terms of both the identity and the relative abundance of constituting taxa) of the associated fauna and the abundance of several taxa (the polychaetes Eulalia ornata, Syllis pulvinata, S. garciai, Nereis splendida and Arabella iricolor, and the amphipods Apolochus neapolitanus, Tethylembos viguieri and Caprella acanthifera) varied among locations established ~50e100 km apart. Syllis pulvinata also showed significant variation between sites (hundreds of metres apart), analogously to the other syllid polychaetes S. armillaris and S. gracilis, the nereidid polychaete Nereis rava, and the amphipod Gammaropsis ulrici. The largest variance of S. spinulosa, of the structure of the whole associated fauna and of 56% of taxa analysed individually occurred at the scale of replicates (metres apart), while that of the dominant bio-constructor S. alveolata and of 25% of taxa occurred at the scale of sites. The remaining 19% and the total richness of taxa showed the largest variance at the scale of locations. Present findings contribute to meet a crucial requirement of any future effective protection strategy, i.e., identifying relevant scales of variation to be included in protection schemes aiming at preserving representative samples not only of target habitats and organisms, but also of the processes driving such variabilit

Year-round variation in the isotopic niche of Scopoli's shearwater (Calonectris diomedea) breeding in contrasting sea regions of the Mediterranean Sea

Top marine predators are key components of marine food webs. Among them, long-distance migratory seabirds, which travel across different marine ecosystems over the year, may experience important year-round changes in terms of oceanographic conditions and availability of trophic resources. We tested whether this was the case in the Scopoli's shearwater (Calonectris diomedea), a trans-equatorial migrant and top predator, by sampling birds breeding in three environmentally different regions of the Mediterranean Sea. The analysis of positional data and stable isotopes (δ1³C and δ15N) of target feathers revealed that birds from the three regions were spatially segregated during the breeding period while they shared non-breeding areas in the Atlantic Ocean. Isotopic baseline levels of N and C (meso-zooplankton) were significantly different among marine regions during breeding. Such variation was reflected at the higher trophic levels of pelagic and demersal fish muscles as well as in shearwater feathers grown in the Mediterranean. δ15N- and δ13C-adjusted values of shearwaters were significantly different among populations suggesting that birds from different breeding areas relied on prey species from different trophic levels. Conversely, the non-breeding spatial and isotopic niches overlapped greatly among the three populations. Shearwater trophic niches during breeding were narrower and segregated compared to the non-breeding period, revealing a high plasticity in trophic resource use. Overall, this study highlights seasonal and region-specific use of trophic resources by Scopoli's shearwater, suggesting a broad trophic plasticity and possibly a high adaptability to environmental changes

Microplastics impair the feeding performance of a Mediterranean habitat-forming coral

none9siThe impact of plastic debris, and in particular of microplastics (here referred as particles smaller than 5 mm) on aquatic environments has now become a topic of raising concern. Microplastics are particularly abundant in the Mediterranean Sea, potentially exerting substantial pressures on marine organisms at different levels of organization. Ingestion of microplastics has been observed in a large number of marine species. The aim of this work is to test if microplastics produce a feeding impairment in Astroides calycularis, a shallow water, habitat-forming coral endemic to the Mediterranean Sea. Our findings suggest a lack of any avoidance mechanism allowing the polyps to discern between food items and microplastics when occurring simultaneously. Moreover, polyps spend a considerable amount of time on handling microplastic particles. As a consequence, microplastics impair the feeding efficiency in A. calycularis, since polyps may not be fully able to profit from the drifting plankton aggregations. Therefore, we suggest that microplastics can cause a reduction of fitness in A. calycularis, and presumably also in other species characterized by suspension feeding strategy.embargoed_20220123Savinelli B.; Vega Fernandez T.; Galasso N.M.; D'Anna G.; Pipitone C.; Prada F.; Zenone A.; Badalamenti F.; Musco L.Savinelli, B.; Vega Fernandez, T.; Galasso, N. M.; D'Anna, G.; Pipitone, C.; Prada, F.; Zenone, A.; Badalamenti, F.; Musco, L

Interactive effects of fishing effort reduction and climate change in a central Mediterranean fishing area: Insights from bio-economic indices derived from a dynamic food-web model

Disentangling the effects of mixed fisheries and climate change across entire food-webs requires a description of ecosystems using tools that can quantify interactive effects as well as bio-economic aspects. A calibrated dynamic model for the Sicily Channel food web, made up of 72 functional groups and including 13 fleet segments, was developed. A temporal simulation until 2050 was conducted to evaluate the bio-economic interactive effects of the reduction of bottom trawling fishing effort by exploring different scenarios that combine fishery and climate change. Our results indicate that direct and indirect effects produce a net increase in biomass of many functional groups with immediate decline of trawlers’ catches and economic incomes, followed by a long term increase mainly due to biomass rebuilding of commercial species which lasts 5-10 years after fishing reduction. Synergistic and antagonistic effects caused by changes in the fishing effort and in climate characterize a specific functional group’s response in biomass which, in turn, modulate also the catch and income of the other fleets, and especially of those sharing target resources. However, trawler’s intra-fleet competition is higher than the others fleet effects. In the medium term, the effects of fishing effort reduction are higher than those of climate change and seem to make exploitation of marine resources more sustainable over time and fishery processes more efficient by improving ecosystem health

Lack of Correlation between Liver Tests Abnormalities and Trabectedin Efficacy in the Treatment of Soft Tissue Sarcoma: A Retrospective Study

Elevation in liver transaminases is common in patients treated with the marine antitumor agent trabectedin. However, the impact of trabectedin-related transaminase elevations on treatment outcomes is unclear. This retrospective study investigated the correlation between liver tests abnormalities and treatment outcomes in patients with unresectable advanced or metastatic soft tissue sarcomas (STS) treated with trabectedin 1.5 mg/m2 once every 3 weeks at three reference centers in Italy. The effect of grade 3/4 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) during the first two cycles and at any time during trabectedin treatment on progression-free survival (PFS) and overall survival (OS) were analyzed. Liver tests abnormalities during the first two cycles of chemotherapy or at any time during trabectedin treatment did not significantly affect PFS or OS. Nor were survival outcomes significantly different in the subgroups of patients with or without ALT/AST increases or with ALT/AST elevations ≥15 × the upper limit of normal (ULN) versus those with ALT/AST elevation <15 × ULN. Although liver tests abnormalities are common in patients treated with trabectedin, elevations in ALT and AST are usually transient, occur during the first two cycles of treatment, and do not appear to affect survival

Assessment of the Sabellaria alveolata reefs’ structural features along the Southern coast of Sicily (Strait of Sicily, Mediterranean Sea)

The honeycomb worm Sabellaria alveolata is a gregarious tube-dwelling polychaete that builds remarkable biogenic reefs in marine coastal waters. Sabellaria alveolata reefs are considered valuable marine habitats requiring protection measures for their conservation, as they play a key role in the functioning of coastal ecosystems. Sabellarid reefs are extensively developed along the Atlantic coasts of Europe and reported for the Mediterranean Sea and the Italian coasts, where large reefs have been recorded in several localities. Fragmentary information is available on their health status, Sabellaria reefs thus being listed as “Data Deficient” in the Red List of Marine Habitats. To fill this knowledge gap, this study focused on the analysis of the structure of three reefs found along the southern coast of Sicily. In particular, we aimed to assess their phases with respect to the natural cycle that characterizes the sabellarid reefs. Reef features were analyzed both on the macroscale, based on the bioconstruction size (diameter and thickness) and degree of fragmentation, and on the microscale, based on the measurement of worm density, opercular length and sand porch presence. This study reveals relevant differences among reefs of the studied locations. These differences we attribute to the temporal shift linked to the natural reef phases, albeit further analyses are needed to understand the possible effect of natural and anthropogenic sources of variation on the Southern Sicilian reefs. In conclusion, Sabellaria reefs are a unique and persistent habitat along the Sicilian coast requiring proper management and conservation measures

Recent advances in desmoid tumor therapy

The desmoid tumor is a locally aggressive proliferative disease within the family of soft-tissue sarcomas. Despite its relatively good prognosis, the clinical management of desmoid tumors requires constant multidisciplinary evaluation due to its highly variable clinical behavior. Recently, active surveillance has being regarded as the appropriate strategy at diagnosis, as indolent persistence or spontaneous regressions are not uncommon. Here, we review the most recent advances in desmoid tumor therapy, including low-dose chemotherapy and treatment with tyrosine kinase inhibitors. We also explore the recent improvements in our knowledge of the molecular biology of this disease, which are leading to clinical trials with targeted agents

Type and gene location of kit mutations predict progression-free survival to first-line imatinib in gastrointestinal stromal tumors: A look into the exon

In previous studies on localized GISTs, KIT exon 11 deletions and mutations involving codons 557/558 showed an adverse prognostic influence on recurrence-free survival. In the metastatic setting, there are limited data on how mutation type and codon location might contribute to progression-free survival (PFS) variability to first-line imatinib treatment. We analyzed the type and gene location of KIT and PDGFRA mutations for 206 patients from a GIST System database prospectively collected at an Italian reference center between January 2005 and September 2020. By describing the mutational landscape, we focused on clinicopathological characteristics according to the critical mutations and investigated the predictive role of type and gene location of the KIT exon 11 mutations in metastatic patients treated with first-line imatinib. Our data showed a predictive impact of KIT exon 11 pathogenic variant on PFS to imatinib treatment: patients with deletion or insertion/deletion (delins) in 557/558 codons had a shorter PFS (median PFS: 24 months) compared to the patients with a deletion in other codons, or duplication/insertion/SNV (median PFS: 43 and 49 months, respectively) (p &lt; 0.001). These results reached an independent value in the multivariate model, which showed that the absence of exon 11 deletions or delins 557/558, the female gender, primitive tumor diameter (≤5 cm) and polymorphonuclear leucocytosis (&gt;7.5 109/L) were significant prognostic factors for longer PFS. Analysis of the predictive role of PDGFRA PVs showed no significant results. Our results also confirm the aggressive biology of 557/558 deletions/delins in the metastatic setting and allow for prediction at the baseline which GIST patients would develop resistance to first-line imatinib treatment earlier