1,128 research outputs found

    Commentary on "a case of paratesticular leiomyosarcoma successfully treated with orchiectomy and chemotherapy"

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    We have read with great interest the article written by Ko and colleagues on a particularly rare type of malignant mesenchymal tumor that is paratesticular leiomyosarcoma and we did appreciate the argumentation on the utility of adjuvant chemotherapy as treatment of stage III disease. As for our experience, we would like to shed light on a very rare and little-known aspect surrounding this neoplasm, which is the capability of dedifferentiation exerted in order to recur or metastasize

    The Italian Business Cycle; Coincident and Leading Indicators and Some Stylized Facts

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    This paper analyses the business cycle properties of 183 time series relevant to the Italian economy, including real, monetary and international variables. We propose new monthly coincident and leading composite indicators for the Italian business cycle; the leading indicator anticipates the turning points of the coincident indicator on average by six months. On the methodological side, the study provides a scheme for constructing cyclical indicators on a sound statistical basis through iterative steps, combining the use of traditional NBER methods with that of more recent techniques of cyclical analysis. A number of stylized facts of the Italian business cycle emerge. Among them, money and financial variables are found to lead the cycle, chronologically, by an average of between one year and sixteen months. There is also strong evidence of synchronization of international cycles, with the US and UK cycles leading the Italian cycle by two to three quarters. The main linking channel seems to be trade, with Italian exports to EU countries leading the cycle by six months on average.business cycles, cyclical indicators, leading indicators, Italian stylized fact

    Ion channel expression in human melanoma samples. in silico identification and experimental validation of molecular targets

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    Expression of 328 ion channel genes was investigated, by in silico analysis, in 170 human melanoma samples and controls. Ninety-one members of this gene-family (i.e., about 28%) show a significant (p 0.90 and p 90% in most cases). Such five genes (namely, SCNN1A, GJB3, KCNK7, GJB1, KCNN2) are novel potential melanoma markers or molecular targets, never previously related to melanoma. The “druggable genome” analysis was then carried out. Miconazole, an antifungal drug commonly used in clinics, is known to target KCNN2, the best candidate among the five identified genes. Miconazole was then tested in vitro in proliferation assays; it dose-dependently inhibited proliferation up to 90% and potently induced cell-death in A-375 and SKMEL-28 melanoma cells, while it showed no effect in control cells. Moreover, specific silencing of KCNN2 ion channel was achieved by siRNA transfection; under such condition miconazole strongly increases its anti-proliferative effect. In conclusion, the present study identified five ion channels that can potentially serve as sensitive and specific markers in human melanoma specimens and demonstrates that the antifungal drug miconazole, known to target one of the five identified ion channels, exerts strong and specific anti-melanoma effects in vitro

    adding pertuzumab to adjuvant therapy for high risk her2 positive early breast cancer in aphinity a grade analysis

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    Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population

    Agnostic evaluation of ipilimumab and nivolumab association: a metanalysis

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    Background: Ipilimumab and Nivolumab, targeting the molecules CTLA-4, PD-1, respectively,have shown efficacy against several types of cancer. Despite these results, only a small percentage of patients maintains a long-lasting effect. Even Ipilimumab, in combination with nivolumab, has demonstrated a significant clinical benefit in multiple tumor types. However, no trial has been designed with the primary endpoint to compare the efficacy of nivolumab plus ipilimumab combined, compared to nivolumab alone. Hence, the added value of ipilimumab in the combination has not clearly been established yet. The aim of this study was to demonstrate the superiority of the combination strategy compared to the single agent therapy. Materials and methods: We performed a meta-analysis of Phase I-II-III Clinical Trials, published from 2010 up to 2020, in which the combination of ipilimumab plus nivolumab was compared to nivolumab alone. We extracted ORR, OS and PFS HR on the basis of treatment from the subgroup analysis of each trial. Results: A total of 7 trials were included in the present meta-analysis. Overall, 1313 patients were treated with the nivolumab plus ipilimumab combination compared to 1110 patients treated with nivolumabalone. All trials reported the Objective response rate(ORR), no heterogeneity was found among studies and the pooled Odds Ratio was highly in favor of the nivolumab plus ipilimumab combination with respect to nivolumab alone (1.683; 95% CI: 1.407-2.012; P < 0.0001). Three studies were considered for Progression free survival (PFS) analysis, and the pooled Hazard Ratio favored the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.807; 95% CI: 0.719-0.907; P < 0.0001). The Overall survival(OS) endpoint was considered only in 2 trials, and the pooled HR favored, also in this case, the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.87; 95% CI: 0.763-0.997; P = 0.045)

    Observations on the Enamel of Odontomas

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    The morphological study of odontomas provides an alternative model for observing the formation of dental tissues, since different maturing stages are present simultaneously. Investigations were performed on decalcified samples (using light microscopy and transmission electron microscopy) and on undecalcified samples of complex odontoma enamel (using transmission electron microscopy). Simultaneous presence of prismatic enamel at various maturing stages with different structural characteristics was observed. Such enamel was sometimes associated with layers of ameloblastic cells with characteristics of cells in functional activity. In other sites, the enamel did not present a prismatic structure but it appeared as unstructured material clusters with abundant organic component. It was concluded that the theory according to which an ecto-mesenchymal inductive failure occurs in odontomas is not confirmed. The defect seen at the beginning of the differentiated and anomalous tissue maturation may be related to latest events in the development of the enamel organ. In this regard, it was concluded that such events involve the efficiency of the ameloblasts and the possible alterations in the organic matrix

    Degradation rate of 5-fluorouracil in metastatic colorectal cancer. A new predictive outcome biomarker?

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    BACKGROUND: 5-FU based chemotherapy is the most common first line regimen used for metastatic colorectal cancer (mCRC). Identification of predictive markers of response to chemotherapy is a challenging approach for drug selection. The present study analyzes the predictive role of 5-FU degradation rate (5-FUDR) and genetic polymorphisms (MTHFR, TSER, DPYD) on survival. MATERIALS AND METHODS: Genetic polymorphisms of MTHFR, TSER and DPYD, and the 5-FUDR of homogenous patients with mCRC were retrospectively studied. Genetic markers and the 5-FUDR were correlated with clinical outcome. RESULTS: 133 patients affected by mCRC, treated with fluoropyrimidine-based chemotherapy from 2009 to 2014, were evaluated. Patients were classified into three metabolic classes, according to normal distribution of 5-FUDR in more than 1000 patients, as previously published: poor-metabolizer (PM) with 5-FU-DR ≤ 0,85 ng/ml/106 cells/min (8 pts); normal metabolizer with 0,85 < 5-FU-DR < 2,2 ng/ml/106 cells/min (119 pts); ultra-rapid metabolizer (UM) with 5-FU-DR ≥ 2,2 ng/ml/106 cells/min (6 pts). PM and UM groups showed a longer PFS respect to normal metabolizer group (14.5 and 11 months respectively vs 8 months; p = 0.029). A higher G3-4 toxicity rate was observed in PM and UM, respect to normal metabolizer (50% in both PM and UM vs 18%; p = 0.019). No significant associations between genes polymorphisms and outcomes or toxicities were observed. CONCLUSION: 5-FUDR seems to be significantly involved in predicting survival of patients who underwent 5-FU based CHT for mCRC. Although our findings require confirmation in large prospective studies, they reinforce the concept that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes

    Recovery of Cork Manufacturing Waste within Mortar and Polyurethane: Feasibility of Use and Physical, Mechanical, Thermal Insulating Properties of the Final Green Composite Construction Materials

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    The valorization of industrial waste is a hot topic toward circular economy and sustainability. Several wastes have been proposed as resources for different production processes; however, others are still disposed to landfill or waste-to-energy plants. For the first time, this work suggests a sustainable alternative to managing cork waste from bottle caps manufacturing; this is generated by a local company at about 220,000 m3/year. The powder waste has a 0.063–1 mm particle size and is mainly composed of cork, polyurethane adhesive, and paraffin. Its valorization is proposed as filler in construction materials such as lime-based mortar (1–4 wt%) and polyurethane (5–15 wt%). Thermal, spectroscopic, and physical characterizations are performed on the cork waste, and mainly result in a low apparent density (340 kg/m3) and high-water absorption (177%). Cork properties allow consideration of extra water in the mortar mix and improve lightness without significantly affecting compressive, bending strength, and thermal insulation. Cork waste in polyurethanes promotes a color change, slightly increases the density (up to 12.5%), and still results in producing a thermally insulating material (&lt;0.06 W/mK). Considering the promising results, this study demonstrates the feasibility of using the manufacturing waste from cork bottle caps to produce green construction materials, thus upgrading it from waste to secondary raw material
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