The effects of zoledronate on monocyte-derived dendritic cells from melanoma patients differ depending on the clinical stage of the disease.

Zoledronic acid has shown indirect anticancer effects on angiogenesis, the tumor microenvironment and immune responses. Its immunological action is exerted, at least in part, via its modulating properties. The aim of this study was to investigate the in vitro effects of zoledronic acid on the dendritic cells of melanoma patients. Peripheral blood samples were collected from 26 patients with melanoma and 11 healthy donors. Dendritic cells were derived from purified monocytes, and zoledronic acid (ZA) was added on the first day of culture. The phenotype and function of the generated cells were evaluated by flow cytometry. The ZA-treated monocytes from patients with early-stage disease generated DCs characterized by reduced endocytic activity and increased allostimulatory capacity compared with the untreated samples, allowing restoration of the DC function observed in normal subjects. In contrast, the ZA-treated monocytes from patients at stage III generated cells with higher CD14 antigen expression and endocytosis than the untreated samples. Therefore, in melanoma patients, the in vitro ZA effects differ according to the progression of the disease. In addition, our preliminary results appear to suggest that ZA effects are also influenced by the expression of CD14 antigen, indicating that the DC phenotype together with clinical characteristics must be considered in the choice of patients to be treated with ZA. Our work focus on the effect of ZA on monocyte-derived DCs from melanoma patients, showing that the effects of therapeutic doses of this drug might be mediated at least in part by modulation of myeloid cell function

Adsorption Capabilities of Fungoid Chitosan Toward Organic Acids in Model Solutions and White Wine

In oenology, fungoid chitosan (CH) can be used as an adjuvant for microbial control, haziness prevention, metal chelation, and ochratoxin removal. In acidic media (such as wine), CH can ionise and interact with charged compounds, giving rise to a series of adsorption and/or removal phenomena, some of which potentially impairing the overall quality of wines. In this context, it is worth noting that the interaction between CH and acidic components of wines has been poorly studied so far, and detailed information on this subject is still lacking. To study those interactions, different doses of chitosan (0.5; 1.0; 2.0 g/L) were dispersed in hydro-alcoholic solution (HS), synthetic wine solution (SW), and white wine (W). Results demonstrated that the remotion of tartaric acid and the change of pH were strongly affected by the matrix and dosage. In W and SW, chitosan was found to adsorb tartaric acid up to about 200 mg/g and 350 mg/g CH, respectively. Accordingly, pH values increased; however, the magnitude depended on the matrix as a consequence of different buffer capacities. Interestingly, even in the absence of tartaric acid (e.g. in HS samples) CH addition caused a pH increase (up to 1.2 units for 2 g/L CH addition) which demonstrated that pH variations may not only depend on the amount of organic acids adsorbed. The chitosan dispersed in W showed the highest average diameter D [3,2] (127.96 μm) compared to the ones dispersed in SW (120.81 μm) and in HS (116.26 μm), probably due to the presence of organic acids on the polymer surface. The minor removal of tartaric acid in W compared to SW could probably depend on the competitive adsorption onto chitosan of other families of compounds present in wine such as polyphenols. The data suggested that chitosan addition could affect the pH and organic acid concentration of all matrices, depending on the doses and composition of the solutions

EFSUMB Recommendations and Guidelines for Gastrointestinal Ultrasound - Part 1: Examination Techniques and Normal Findings (Short version)

Abstract ▼ In October 2014 the European Federation of Societies for Ultrasound in Medicine and Biology formed a Gastrointestinal Ultrasound (GIUS) task force group to promote the use of GIUS in a clinical setting. One of the main objectives of the task force group was to develop clinical recommendations and guidelines for the use of GIUS under the auspices of EFSUMB. The first part, gives an overview of the examination techniques for GIUS recommended by experts in the field. It also presents the current evidence for the interpretation of normal sonoanatomical and physiological features as examined with different ultrasound modalities

SKI-1 and Furin Generate Multiple RGMa Fragments that Regulate Axonal Growth

SummaryThe nervous system is enormously complex, yet the number of cues that control axonal growth is surprisingly meager. Posttranslational modifications amplify diversity, but the degree to which they are employed is unclear. Here, we show that Furin and SKI-1 combine with autocatalytic cleavage and a disulfide bridge to generate four membrane-bound and three soluble forms of the repulsive guidance molecule (RGMa). We provide in vivo evidence that these proprotein convertases are involved in axonal growth and that RGMa cleavage is essential for Neogenin-mediated outgrowth inhibition. Surprisingly, despite no sequence homology, N- and C-RGMa fragments bound the same Fibronectin-like domains in Neogenin and blocked outgrowth. This represents an example in which unrelated fragments from one molecule inhibit outgrowth through a single receptor domain. RGMa is a tethered membrane-bound molecule, and proteolytic processing amplifies RGMa diversity by creating soluble versions with long-range effects as well

Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy.

The expression of epidermal growth factor receptor (EGFR), oestrogen receptor (ER) and progesterone receptor (PR) was assayed by a radioreceptor method in 117 primary ovarian cancers. EGFR was not significantly related to any of the clinicopathological parameters examined. In patients with stage II-IV disease who underwent second-look surgery after primary chemotherapy, a significant correlation between high EGFR levels and poor response to chemotherapy was demonstrated (P = 0.031). Moreover, post-operative residual tumour showed an independent role in predicting chemotherapy response (P = 0.0007) and EGFR status showed a borderline significance (P = 0.052) in the multivariate analysis. No correlation between steroid hormone receptors and clinicopathological parameters was observed. Whereas a significant relationship was shown between EGFR positivity and a shorter overall survival (OS) (P = 0.0022) and progression-free survival (PFS) (P = 0.0033), patient survival was not related to steroid hormone receptor status. Among the parameters tested only stage, ascites and EGFR status retained an independent prognostic value in the multivariate analysis

Identification of plasma microRNAs as new potential biomarkers with high diagnostic power in human cutaneous melanoma

Melanoma is a devastating disease with few therapeutic options in the advanced stage and with the urgent need of reliable biomarkers for early detection. In this context, circulating microRNAs are raising great interest as diagnostic biomarkers. We analyzed the expression profiles of 21 selected microRNAs in plasma samples from melanoma patients and healthy donors to identify potential diagnostic biomarkers. Data analysis was performed using global mean normalization and NormFinder algorithm. Linear regression followed by receiver operating characteristic analyses was carried out to evaluate whether selected plasma miRNAs were able to discriminate between cases and controls. We found five microRNAs that were differently expressed among cases and controls after Bonferroni correction for multiple testing. Specifically, miR-15b-5p, miR-149-3p, and miR-150-5p were up-regulated in plasma of melanoma patients compared with healthy controls, while miR-193a-3p and miR-524-5p were down-regulated. Receiver operating characteristic analyses of these selected microRNAs provided area under the receiver operating characteristic curve values ranging from 0.80 to 0.95. Diagnostic value of microRNAs is improved when considering the combination of miR-149-3p, miR-150-5p, and miR-193a-3p. The triple classifier had a high capacity to discriminate between melanoma patients and healthy controls, making it suitable to be used in early melanoma diagnosis

Melanoma in the Italian population and regional environmental influences: A national retrospective survey on 2001–2008 hospitalization records

Objective: To assess the burden of regional environmental factors influencing the incidence of Melanoma in the Italian population and overcome the problem of partial population coverage by local cancer registries and thematic archives. Methods: We analyzed the Italian national hospitalization records from 2001 to 2008 provided by the Ministry of Health, excluding hospital re-admissions of the same patients, in order to assess the occurrence of Melanoma over a 8-year period. Data were presented by age groups (absolute number of cases from 20 to ≥80 years old) and per Region (rates per 100,000 inhabitants) for each year. Results: The overall number of new hospitalizations due to malignant Melanoma increased by 16.8% from 2001 (n = 4846) to 2008 (n = 5823), with the rate per 100,000 inhabitants passing from 10.5 to almost 12.0 at a national level. The majority of new diagnoses of malignant Melanoma was observed in two age groups: 61–70 years old (from 979 in 2001 up to 2109 in 2008, corresponding to 15.1 and 18.1 new cases per 100,000 inhabitants, respectively) and 71–80 years old (from 954 in 2001 up to 1141 in 2008, corresponding to 19.5 and 21.8 new cases per 100,000 inhabitants, respectively). The number of hospitalizations due to Melanoma increased in all age groups with the only exception of the youngest patients aged 20–30 years old. The highest increases over the 8-year period were observed in people aged ≥81 years old (+34%), 61–70 years old (+20%) and surprisingly in the age group 31–40 years old (+17%). Southern Regions showed lower hospitalization rates compared to Northern Italy and Region Lazio. The highest increases between 2001 and 2008 were observed in Trentino/Alto Adige, Friuli Venezia Giulia, Valla d’Aosta and Veneto Region. Conclusions: Hospitalizations due to malignant Melanoma in Italy seem to be influenced by environmental or population-related factors showing a decreasing incidence rate from the Northern to Southern Regions

Structure and reorientational dynamics of 1-F-adamantane

The polymorphism and the dynamics of a simple rigid molecule (1-fluoro-adamantane) have been studied by means of X-ray powder diffraction and broadband dielectric spectroscopy. At temperatures below the melting point, the molecule forms an orientationally disordered Phase I with a cubic-centered structure (Phase I, Fm (3) over barm, Z = 4). This phase possesses eight equilibrium positions for the fluorine atom, with equal occupancy factors of 1/8. A solid-solid phase transition to a low-temperature tetragonal phase (Phase II, P (4) over bar2(1)c, Z = 2) reduces the statistical disorder to only four possible equivalent sites for the fluorine atom, with fractional occupancies of 1/4. The dynamics has been rationalized under the constraints imposed by the space group of the crystal structure determined by powder X-ray diffraction. The dielectric spectroscopy study reveals that the statistical disorder in Phase II is dynamic in character and is associated with reorientational jumps along the two-and three-fold axes. In the dielectric loss spectra, the cooperative (alpha) relaxation exhibits a shoulder on the high-frequency side. This remarkable finding clearly reveals the existence of two intrinsic reorientational processes associated with the exchange of the F atom along the four sites. In addition to suchPeer ReviewedPostprint (published version