Theranostic application of miR-429 in HER2+ breast cancer

Human epidermal growth factor receptor 2 (HER2) is overexpressed/amplified in one third of breast cancers (BCs), and is associated with the poorer prognosis and the higher metastatic potential in BC. Emerging evidences highlight the role of microRNAs (miRNAs) in the regulation of several cellular processes, including BC. Methods: Here we identified, by in silico approach, a group of three miRNAs with central biological role (high degree centrality) in HER2+ BC. We validated their dysregulation in HER2+ BC and we analysed their functional role by in vitro approaches on selected cell lines and by in vivo experiments in an animal model. Results: We found that their expression is dysregulated in both HER2+ BC cell lines and human samples. Focusing our study on the only upregulated miRNA, miR-429, we discovered that it acts as an oncogene and its upregulation is required for HER2+ cell proliferation. It controls the metastatic potential of HER2+ BC subtype by regulating migration and invasion of the cell. Conclusions: In HER2+ BC oncogenic miR-429 is able to regulate HIF1\u3b1 pathway by directly targeting VHL mRNA, a molecule important for the degradation of HIF1\u3b1. The overexpression of miR-429, observed in HER2+ BC, causes increased proliferation and migration of the BC cells. More important, silencing miR-429 succeeds in delaying tumor growth, thus miR-429 could be proposed as a therapeutic probe in HER2+ BC tumors

P132 Uncovering blood biomarkers of Inflammatory Bowel Diseases by Raman spectroscopy and FAP dosage: toward a noninvasive triage of patients in first care diagnostic

Abstract Background Currently, a major point of concern in the management of Inflammatory Bowel Diseases (IBD) is the absence of accurate and specific circulating biomarkers able to drive diagnosis in a timely and noninvasive manner. Aim of the present study was to explore blood biomarkers of IBD by coupling the targeted detection of circulating fibroblast activation protein (FAP), a recognized valuable marker of bowel lesion in IBD, and Raman spectroscopy (RS), a quick and label-free metabolomic technique that provides a real-time biochemical characterization of plasma samples without any previously known target. Methods Blood samples were collected from over 140 patients with IBD and 170 control subjects matched for gender and age. Isolated plasma was analysed by enzyme-linked immunosorbent assay for quantitative detection of circulating form of FAP. RS was performed on dry droplets of plasma, with the aim to decipher specific fingerprint of IBD in peripheral blood. A predictive model was built on FAP and Raman data separately, to determine specificity, sensitivity and accuracy of the two approaches in patients classification. Supervised multivariate model was applied on a subset of 203 patients to discriminate IBD and control subjects based on combined datasets. Results FAP levels were reduced in patients with IBD as compared to controls (p<0.0001). The sensitivity and specificity of FAP were 70% and 84% based on the optimal cutoff (57.6 ng mL-1, AUC=0.78). Raman spectra of IBD plasma revealed significant differences in peaks corresponding to carotenoids, proteins with β-sheet secondary structure, lipids and aromatic amino-acids. A machine learning model was applied on a subset of patients reaching an accuracy of 85% in classifying IBD and control subjects. No statistically significant differences were observed so far between the discriminative performance of the sole RS or the combination of RS and FAP. Conclusion RS and FAP dosage enable new discoveries in the biological fingerprint of IBD plasma and provide novel candidate biomarkers of IBD. Our preliminary results strongly suggest that novel blood-based approaches could represent a fast noninvasive way to triage patents with suspected IBD in first care diagnostic, to be applied prior to further specific evaluation

Quartz fiber calorimetry

The fundamentals of a new electromagnetic and hadronic sampling calorimetry based on the detection of Cherenkov light generated in quartz optical fibers are presented. Optical fibers transport light only in a selected angular range which results in a non-obvious and absolutely unique characteristic for this new technique: showers of very narrow visible energy. In addition, the technique is characterized by radiation resistance measured in Gigarads and nanosecond signal duration. Combined, these properties make quartz fiber calorimetry a very promising technique for high intensity heavy ion experiments and for the high pseudorapidity regions of high intensity collider experiments. The results of beam tests and simulations are used to illustrate the basic properties and peculiar characteristics of this recent development

A new measurement of J/psi suppression in Pb-Pb collisions at 158 GeV per nucleon

We present a new measurement of J/psi production in Pb-Pb collisions at 158 GeV/nucleon, from the data sample collected in year 2000 by the NA50 Collaboration, under improved experimental conditions with respect to previous years. With the target system placed in vacuum, the setup was better adapted to study, in particular, the most peripheral nuclear collisions with unprecedented accuracy. The analysis of this data sample shows that the (J/psi)/Drell-Yan cross-sections ratio measured in the most peripheral Pb-Pb interactions is in good agreement with the nuclear absorption pattern extrapolated from the studies of proton-nucleus collisions. Furthermore, this new measurement confirms our previous observation that the (J/psi)/Drell-Yan cross-sections ratio departs from the normal nuclear absorption pattern for semi-central Pb-Pb collisions and that this ratio persistently decreases up to the most central collisions.Comment: 19 pages, 10 figures. Submitted to Eur. Phys. J.

J/psi azimuthal anisotropy relative to the reaction plane in Pb-Pb collisions at 158 GeV per nucleon

The J/$\psi$ azimuthal distribution relative to the reaction plane has been measured by the NA50 experiment in Pb-Pb collisions at 158 GeV/nucleon. Various physical mechanisms related to charmonium dissociation in the medium created in the heavy ion collision are expected to introduce an anisotropy in the azimuthal distribution of the observed J/$\psi$ mesons at SPS energies. Hence, the measurement of J/$\psi$ elliptic anisotropy, quantified by the Fourier coefficient v$_2$ of the J/$\psi$ azimuthal distribution relative to the reaction plane, is an important tool to constrain theoretical models aimed at explaining the anomalous J/$\psi$ suppression observed in Pb-Pb collisions. We present the measured J/$\psi$ yields in different bins of azimuthal angle relative to the reaction plane, as well as the resulting values of the Fourier coefficient v$_{2}$ as a function of the collision centrality and of the J/$\psi$ transverse momentum. The reaction plane has been estimated from the azimuthal distribution of the neutral transverse energy detected in an electromagnetic calorimeter. The analysis has been performed on a data sample of about 100 000 events, distributed in five centrality or p$_{\rm T}$ sub-samples. The extracted v$_{2}$ values are significantly larger than zero for non-central collisions and are seen to increase with p$_{\rm T}$.Comment: proceedings of HP08 conference corrected a typo in one equatio

The dependence of the anomalous J/psi suppression on the number of participant nucleons

The observation of an anomalous J/psi suppression in Pb-Pb collisions by the NA50 Collaboration can be considered as the most striking indication for the deconfinement of quarks and gluons at SPS energies. In this Letter, we determine the J/psi suppression pattern as a function of the forward hadronic energy E-ZDC measured in a Zero Degree Calorimeter (ZDC). The direct connection between EZDC and the geometry of the collision allows us to calculate, within a Glauber approach, the precise relation between the number of participant nucleons N-part and E-ZDC. Then, we check if the experimental data can be better explained by a sudden or a smooth onset of the anomalous J/psi suppression as a function of the number of participants. (C) 2001 Elsevier Science B.V. All rights reserved.info:eu-repo/semantics/publishedVersio

The ALICE Zero Degree Calorimeters

In the ALICE experiment at Cern LHC, a set of hadron calorimeters will be used to determine the centrality of the Pb-Pb collision. The spectator protons and neutrons, will be separated from the ion beams, using the separator magnet (D1) of the LHC beam optics and respectively detected by a proton (ZP) and a neutron (ZN) "Zero-degree Calorimeter" (ZDC). The detectors will be placed in front of the separator D2 magnet, 115 meters away from the beam intersection point. The ZDCs are quartz-fiber spaghetti calorimeters that exploit the Cherenkov light produced by the shower particles in silica optical fibers.This technique offers the advantages of high radiation hardness (up to several Grad), fast response and reduced lateral dimension of the detectable shower. In addition, quartz-fiber calorimeters are intrinsically insensitive to radio-activation background, which produces particles below the Cherenkov threshold.The ALICE ZDC should have an energy resolution comparable with the intrinsic energy fluctuations, which range from about 20 0.000000or central events to about 5 0.000000or peripheral ones, according to simulations that use HIJING as event generator. The fiber-to-absorber filling ratio must be chosen as a good compromise between the required energy resolution and the fiber cost.The design of the proposed calorimeter will be discussed, together with the expected performances. Whenever possible, the simulated results will be compared with the experimental ones, obtained with the built prototypes and with the NA50 ZDC, which can be considered as a working prototype for the ALICE neutron calorimeter

Bottomonium and Drell-Yan production in p-A collisions at 450 GeV

The NA50 Collaboration has measured heavy-quarkonium production in p-A collisions at 450 GeV incident energy (sqrt(s) = 29.1 GeV). We report here results on the production of the Upsilon states and of high-mass Drell-Yan muon pairs (m > 6 GeV). The cross-section at midrapidity and the A-dependence of the measured yields are determined and compared with the results of other fixed-target experiments and with the available theoretical estimates. Finally, we also address some issues concerning the transverse momentum distributions of the measured dimuons.Comment: 18 pages, 9 figures, to be published in Phys. Lett.

Zero degree Cherenkov calorimeters for the ALICE experiment

International audienceThe collision centrality in the ALICE experiment will be determined by the Zero Degree Calorimeters (ZDCs) that will measure the spectator nucleons energy in heavy ion collisions. The ZDCs detect the Cherenkov light produced by the fast particles in the shower that cross the quartz fibers, acting as the active material embedded in a dense absorber matrix. Test beam results of the calorimeters are presented