High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: pathogenic and clinical relevance

BACKGROUND: Engagement of CD40 promotes survival of undifferentiated nasopharyngeal carcinoma (UNPC) cells and similar effects are induced by the EBV oncoprotein LMP-1 that is expressed in a fraction of cases. Considering that CD40 may be activated also by the soluble isoform of CD40L (sCD40L), we investigated the serum levels of sCD40L in a series of 61 UNPC patients from Italy, a non-endemic area for this disease. RESULTS: At diagnosis, serum samples of UNPC patients contained significantly higher levels of sCD40L than age-matched healthy controls (p < 0.001). High levels of sCD40L (i.e., >18 ng/ml) were more frequently found in patients <40 years of age (p = 0.03) and with distant metastases at presentation (p = 0.03). Serum levels of sCD40L were inversely associated with the expression of the EBV oncoprotein LMP-1 (p = 0.03), which mimics a constitutively activated CD40. The amount of sCD40L decreased in a fraction of patients treated with local radiotherapy alone. Moreover, CD40L(+ )lymphoid cells admixed to neoplastic UNPC cells were detected in cases with high serum levels of sCD40L, suggesting that sCD40L is probably produced within the tumor mass. CONCLUSION: sCD40L may contribute to CD40 activation in UNPC cells, particularly of LMP-1-negative cases, further supporting the crucial role of CD40 signalling in the pathogenesis of UNPC. sCD40L levels may be useful to identify UNPC patients with occult distant metastases at presentation

Unexpected High Response Rate to Traditional Therapy after Dendritic Cell-Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis

We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8–33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy

Stability Program in Dendritic Cell Vaccines: A “Real-World” Experience in the Immuno-Gene Therapy Factory of Romagna Cancer Center

Advanced therapy medical products (ATMPs) are rapidly growing as innovative medicines for the treatment of several diseases. Hence, the role of quality analytical tests to ensure consistent product safety and quality has become highly relevant. Several clinical trials involving dendritic cell (DC)-based vaccines for cancer treatment are ongoing at our institute. The DC-based vaccine is prepared via CD14+ monocyte differentiation. A fresh dose of 10 million DCs is administered to the patient, while the remaining DCs are aliquoted, frozen, and stored in nitrogen vapor for subsequent treatment doses. To evaluate the maintenance of quality parameters and to establish a shelf life of frozen vaccine aliquots, a stability program was developed. Several parameters of the DC final product at 0, 6, 12, 18, and 24 months were evaluated. Our results reveal that after 24 months of storage in nitrogen vapor, the cell viability is in a range between 82% and 99%, the expression of maturation markers remains inside the criteria for batch release, the sterility tests are compliant, and the cell costimulatory capacity unchanged. Thus, the data collected demonstrate that freezing and thawing do not perturb the DC vaccine product maintaining over time its functional and quality characteristics

The 1928 eruption of Mount Etna (Italy): Reconstructing lava flow evolution and the destruction and recovery of the town of Mascali

Abstract Mount Etna in Sicily (Italy) shows more than 2,500 years of interactions between volcanic eruptions and human activity, and these are well documented in historical sources. During the last 400 years, flank eruptions have had major impacts on the urban fabric of the Etna region, especially in 1651, 1669, 1923 and 1928, and it is the last of these which is the focus of this paper. In this paper a detailed field and historical reconstruction of the 1928 eruption is presented which allows three themes to be discussed: the evolution of the flow field, lava volume and average magma discharge rate trend; the eruption's human impact, particularly the destruction of the town of Mascali; and the recovery of the region with re-construction of Mascali in a new location. Detailed mapping of lava flows allowed the following dimensions to be calculated: total area, 4.38 x 106 m2; maximum length, 9.4 km; volume, 52.91 ± 5.21 × 106m3 and an average effusion rate of 38.5 m3 s-1. Time-averaged discharged rates are calculated allowing the reconstruction of their temporal variations during the course of the eruption evidencing a high maximum effusion rate of 374 m3 s-1. These trends, in particular with regard to the Lower Fissure main phase of the eruption, are in accordance with the ‘idealized discharge model’ of Wadge (1981), proposed for basaltic eruptions driven by de-pressurization of magma sources, mainly through reservoir relaxation (i.e. elastic contraction of a magma body). The eruption took place when Italy was governed by Mussolini and the fascist party. The State response both, during and in the immediate aftermath of the eruption and in the years that followed during which Mascali was reconstructed, was impressive. This masked a less benign legacy, however, that can be traced for several subsequent decades of using responses to natural catastrophes to manufacture State prestige by reacting to, rather than planning for, disasters

The large earthquake of 8 August 1303 in Crete: seismic scenario and tsunami in the Mediterranean area

By conducting a historical review of this large seismic event in the Mediterranean, it has been possible to identify both the epicentral area and the area in which its effects were principally felt. Ever since the nineteenth century, the seismological tradition has offered a variety of partial interpretations of the earthquake, depending on whether the main sources used were Arabic, Greek or Latin texts. Our systematic research has involved the analysis not only of Arab, Byzantine and Italian chronicle sources, but also, and in particular, of a large number of never previously used official and public authority documents, preserved in Venice in the State Archive, in the Marciana National Library and in the Library of the Museo Civico Correr. As a result, it has been possible to establish not only chronological parameters for the earthquake (they were previously uncertain), but also its overall effects (epicentral area in Crete, Imax XI MCS). Sources containing information in 41 affected localities and areas were identified. The earthquake also gave rise to a large tsunami, which scholars have seen as having certain interesting elements in common with that of 21 July, 365, whose epicentre was also in Crete. As regards methodology, this research made it clear that knowledge of large historical earthquakes in the Mediterranean is dependent upon developing specialised research and going beyond the territorial limits of current national catalogues.Published55-723T. Storia SismicaJCR Journa

The “exceptional” earthquake of 3 January 1117 in the Verona area (northern Italy): A critical time review and detection of two lost earthquakes (lower Germany and Tuscany)

In the seismological literature the 3 January 1117 earthquake represents an interesting case study, both for the sheer size of the area in which that event is recorded by the monastic sources of the 12th century, and for the amount of damage mentioned. The 1117 event has been added to the earthquake catalogues of up to five European countries (Italy, France, Belgium, Switzerland, the Iberian peninsula), and it is the largest historical earthquake for northern Italy. We have analyzed the monastic time system in the 12th century and, by means of a comparative analysis of the sources, have correlated the two shocks mentioned (in the night and in the afternoon of 3 January) to territorial effects, seeking to make the overall picture reported for Europe more consistent. The connection between the linguistic indications and the localization of the effects has allowed us to shed light, with a reasonable degree of approximation, upon two previously little known earthquakes, probably generated by a sequence of events. A first earthquake in lower Germany (I0 (epicentral intensity) VII–VIII MCS (Mercalli, Cancani, Sieberg), M 6.4) preceded the far more violent one in northern Italy (Verona area) by about 12–13 hours. The second event is the one reported in the literature. We have put forward new parameters for this Veronese earthquake (Io IX MCS, M 7.0). A third earthquake is independently recorded in the northwestern area of Tuscany (Imax VII-VIII MCS), but for the latter event the epicenter and magnitude cannot be evaluated.PublishedB123093T. Storia SismicaJCR Journa

Le città venete e i terremoti: il caso di Padova (1348-1491).

Volume monografico. Atti del I convegno nazionale di studio. Verona, 14-16 dicembre 1995. In Storia dell'Urbanistica/Veneto !, Quaderni di "Storia dell'Urnanistica" diretti da Enrico Guidoni

Comment on \u201cThe Curious Case of the 1346 Earthquake Recorded Only by Very Young Chroniclers\u201d by Romano Camassi and Viviana Castelli

The article by Camassi and Castelli (2013) (hereinafter CC13) deals with the 1346, northern Italy earthquake, one of hundreds of medieval earthquakes that were investigated in Italy from 1983 to 2007. Regrettably, the article does not add any new data but only proposes a revision and a reinterpretation of published materials. CC13 first criticized the variability of magnitude estimates assigned to this earthquake in catalogs published in Italy over the past 20 years, then went so far as to question whether the 1346 earthquake actually occurred. Their analysis, however, is fraught with demonstrable mistakes in the analysis of medieval texts, such that their conclusions are objectionable both from the point of view of historical criticism and from that of historical seismology. Such conclusions may critically affect the assessment of seismic hazard in a heavily populated and industrialized portion of the Po Plain (northern Italy), right at a time when the threat posed by strong earthquakes in this region is being rediscovered by the citizens and by their administrators following the 20 and 29 May 2012, Emilia events (Mw 6.0 and 5.9). As the coauthors of the catalogs being questioned, we feel an obligation to re-establish what is the evidence supporting 1346 being a real major earthquake and why its magnitude is still uncertain

Encoding and computer analysis of macroseismic effects

We propose a method for the encoding and the computer analysis of the macroseismic effects deduced from historical sources allowing the complete formalization of the process of seismic intensity assessment. In the framework of historical sismology we make use of a multi-criteria decisions-support algorithm, based on the theory of the Fuzzy Sets. By analyzing the texts of the available sources for the 1919 Mugello and 1920 Garfagnana earthquakes, we followed a classification criterion which is independent of any macroseismic scale: we “disarrange” each sentence reported on the sources into 5 syntactic elementary components and represent it by a set of alphanumeric codes. This allows us to retain the maximum adherence to the original sources and to avoid forced interpretations and losses of information due to the need of fitting a given description to each observed effect. Moreover this scheme also allows to gather equivalent effects by reassigning them the same code, and to use this new classification in further processing. This procedure could even be seen as an attempt to define a new macroseismic scale on the basis of a statistical counting of different effects occurrences.Published505-5104T. Sismicità dell'ItaliaN/A or not JC