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

Speckle observations of the binary asteroid (22) Kalliope with C2PU/PISCO

We present new speckle measurements of the position of Linus, the satellite of the asteroid (22) Kalliope, obtained at the 1m C2PU-Epsilon telescope on the Plateau de Calern, France. Observations were made in the visible domain with the speckle camera PISCO. We obtained 122 measurements in February-March 2022 and April 2023, with a mean uncertainty close to 10 milli-arcseconds on the angular separation

Raman spectroscopy reveals that biochemical composition of breast microcalcifications correlates with histopathologic features

Breast microcalcifications are a common mammographic finding. Microcalcifications are considered suspicious signs of breast cancer and a breast biopsy is required, however, cancer is diagnosed in only a few patients. Reducing unnecessary biopsies and rapid characterization of breast microcalcifications are unmet clinical needs. In this study, 473 microcalcifications detected on breast biopsy specimens from 56 patients were characterized entirely by Raman mapping and confirmed by X-ray scattering. Microcalcifications from malignant samples were generally more homogeneous, more crystalline, and characterized by a less substituted crystal lattice compared with benign samples. There were significant differences in Raman features corresponding to the phosphate and carbonate bands between the benign and malignant groups. In addition to the heterogeneous composition, the presence of whitlockite specifically emerged as marker of benignity in benign microcalcifications. The whole Raman signature of each microcalcification was then used to build a classification model that distinguishes microcalcifications according to their overall biochemical composition. After validation, microcalcifications found in benign and malignant samples were correctly recognized with 93.5% sensitivity and 80.6% specificity. Finally, microcalcifications identified in malignant biopsies, but located outside the lesion, reported malignant features in 65% of in situ and 98% of invasive cancer cases, respectively, suggesting that the local microenvironment influences microcalcification features. This study confirms that the composition and structural features of microcalcifications correlate with breast pathology and indicates new diagnostic potentialities based on microcalcifications assessment. Significance: Raman spectroscopy could be a quick and accurate diagnostic tool to precisely characterize and distinguish benign from malignant breast microcalcifications detected on mammography

Establishment and Morphological Characterization of Patient-Derived Organoids from Breast Cancer

Background: Patient-derived organoids (PDO) technology represents an emerging tool for the study of tumor biology and drug responsiveness, thus being useful to design personalized medicine approaches. Despite several studies and clinical trials are ongoing using PDO from colorectal and pancreatic cancer, only few research papers have been published exploiting PDO from breast cancer. Here, we have developed a new protocol to establish PDO from surgical and biopsy samples. Furthermore, we have set up also the methodologies adopted for culture and morphological evaluations. Results: Surgical and core biopsy specimens collected from 33 patients with diagnosis of breast cancer have been processed using the protocols here described obtaining PDO from cancerous and healthy mammary tissue (when available) in a quick and easy way with good yields. The more critical aspects influencing the yield were the characteristic of the tissue of origin (healthy vs tumor tissue) and the amount of material obtained after enzymatic digestion process. Success rate from healthy samples was about 20,83%, while this percentage was higher in samples from cancer tissue (i.e. 87,5%). Also the morphological characterization of breast cancer PDO by brightfield and transmission electron microscopy has been reported. Conclusions: Despite obtaining some organoids from a surgical or biopsy specimen is not a difficult procedure, the establishment of a stable organoid line able to grow and replicate, suitable for long-term biobank storage, is not so obvious. A novel, simple and quick procedure to obtain PDO from surgical and biopsy samples is here proposed to achieve high success rate

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

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.

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

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.

Munc18b is an essential gene in mice whose expression is limiting for secretion by airway epithelial and mast cells

Airway mucin secretion and MC (mast cell) degranulation must be tightly controlled for homoeostasis of the lungs and immune system respectively. We found the exocytic protein Munc18b to be highly expressed in mouse airway epithelial cells and MCs, and localized to the apical pole of airway secretory cells. To address its functions, we created a mouse with a severely hypomorphic Munc18b allele such that protein expression in heterozygotes was reduced by∼50%. Homozygous mutant mice were not viable, but heterozygotes showed a ∼50% reduction in stimulated release of mucin from epithelial cells and granule contents from MCs. The defect in MCs affected only regulated secretion and not constitutive or transporter-mediated secretion. The severity of passive cutaneous anaphylaxiswas also reduced by ∼50%, showing that reduction of Munc18b expression results in an attenuation of physiological responses dependent on MC degranulation. The Munc18b promoter is controlled by INR (initiator), Sp1 (specificity protein 1), Ets, CRE (cAMP-response element), GRE (glucocorticoid-response element), GATA and E-box elements in airway epithelial cells; however, protein levels did not change during mucous metaplasia induced by allergic inflammation. Taken together, the results of the present study identifyMunc18b as an essential gene that is a limiting component of the exocytic machinery of epithelial cells and MCs

Influence of Temperature and Humidity on Bakelite Resistivity

Presentation made at RPC99 and submitted to Elsevier PreprintThe use of phenolic or melaminic bakelite as RPC electrodes is widespread. The electrode resistivity is an important parameter for the RPC performance. As recent studies have pointed out, the bakelite resistivity changes with temperature and is influenced by humidity. In order to gain a quantitative understanding on the influence of temperature and humidity on RPC electrodes, we assembled an apparatus to measure resistivity in well-controlled conditions. A detailed description of the experimental set-up as well as the first resistivity measurements for various laminates in different environmental conditions are presented