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

Beyond evidence-based data: Scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma

The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: Planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition. Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidencebased data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC

Carbon stock increases up to old growth forest along a secondary succession in Mediterranean island ecosystems

The occurrence of old-growth forests is quite limited in Mediterranean islands, which have been subject to particularly pronounced human impacts. Little is known about the carbon stocks of such peculiar ecosystems compared with different stages of secondary succession. We investigated the carbon variation in aboveground woody biomass, in litter and soil, and the nitrogen variation in litter and soil, in a 100 years long secondary succession in Mediterranean ecosystems. A vineyard, three stages of plant succession (high maquis, maquis-forest, and forest-maquis), and an old growth forest were compared. Soil samples at two soil depths (0-15 and 15-30 cm), and two litter types, relatively undecomposed and partly decomposed, were collected. Carbon stock in aboveground woody biomass increased from 6 Mg ha-1 in the vineyard to 105 Mg ha-1 in old growth forest. Along the secondary succession, soil carbon considerably increased from about 33 Mg ha-1 in the vineyard to about 69 Mg ha-1 in old growth forest. Soil nitrogen has more than doubled, ranging from 4.1 Mg ha-1 in the vineyard to 8.8 Mg ha-1 in old growth forest. Both soil parameters were found to be affected by successional stage and soil depth but not by their interaction. While the C/N ratio in the soil remained relatively constant during the succession, the C/N ratio of the litter strongly decreased, probably following the progressive increase in the holm oak contribution. While carbon content in litter decreased along the succession, nitrogen content slightly increased. Overall, carbon stock in aboveground woody biomass, litter and soil increased from about 48 Mg ha-1 in the vineyard to about 198 Mg ha-1 in old growth forest. The results of this study indicate that, even in Mediterranean environments, considerable amounts of carbon may be stored through secondary succession processes up to old growth forest.The occurrence of old-growth forests is quite limited in Mediterranean islands, which have been subject to particularly pronounced human impacts. Little is known about the carbon stocks of such peculiar ecosystems compared with different stages of secondary succession. We investigated the carbon variation in aboveground woody biomass, in litter and soil, and the nitrogen variation in litter and soil, in a 100 years long secondary succession in Mediterranean ecosystems. A vineyard, three stages of plant succession (high maquis, maquis-forest, and forest-maquis), and an old growth forest were compared. Soil samples at two soil depths (0-15 and 15-30 cm), and two litter types, relatively undecomposed and partly decomposed, were collected. Carbon stock in aboveground woody biomass increased from 6 Mg ha(-1) in the vineyard to 105 Mg ha(-1) in old growth forest. Along the secondary succession, soil carbon considerably increased from about 33 Mg ha(-1) in the vineyard to about 69 Mg ha(-1) in old growth forest. Soil nitrogen has more than doubled, ranging from 4.1 Mg ha(-1) in the vineyard to 8.8 Mg ha(-1) in old growth forest. Both soil parameters were found to be affected by successional stage and soil depth but not by their interaction. While the C/N ratio in the soil remained relatively constant during the succession, the C/N ratio of the litter strongly decreased, probably following the progressive increase in the holm oak contribution. While carbon content in litter decreased along the succession, nitrogen content slightly increased. Overall, carbon stock in aboveground woody biomass, litter and soil increased from about 48 Mg ha(-1) in the vineyard to about 198 Mg ha(-1) in old growth forest. The results of this study indicate that, even in Mediterranean environments, considerable amounts of carbon may be stored through secondary succession processes up to old growth forest

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

Hairy garlic (Allium subhirsutum) from Sicily (Italy): LC-DAD-MSn analysis of secondary metabolites and in vitro biological properties

Allium subhirsutum, known as hairy garlic, is a bulbous plant widespread in the Mediterranean area and locally used as a food and spice. In the present study, the chemical profile of the ethanolic extracts from bulbs (BE) and aerial parts (APE) were analyzed by HPLC-ESI-MSn, and antioxidant properties were evaluated by DPPH, ABTS and TEAC assays. The traditional use in the diet, and the well documented biological activity of Allium species suggest a potential as a new nutraceutical. For this reason, the potential usefulness of this food can be considered in the treatment and prevention of degenerative Alzheimer disease. For this reason, acetylcholinesterase inhibitory property was investigated. Furthermore, due to the observed presence of sulfur-containing and phenolic constituents, the cytotoxicity on tumor cells line was investigated. Results revealed significant AChE inhibitory activity for BE and APE. Both extracts exhibited also moderate antioxidant properties in the in vitro assays. Finally, limited cytotoxic activity was observed towards Human colon carcinoma and adenocarcinoma cell line, with differences between the individual parts tested. HPLC-ESI-MSn analysis showed that hairy garlic is a good source of sulphur compounds, flavonoids and phenylpropanoids derivatives, thus being a valid alternative to the common garlic (A. sativum). This work opens new opportunities for the application of A. subhirsutum as a health-promoting food

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

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

Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy

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