223 research outputs found

    Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis.

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    Barretts esophagus (BE) involves a metaplastic replacement of native esophageal squamous epithelium (Sq) by columnar-intestinalized mucosa, and it is the main risk factor for Barrett-related adenocarcinoma (BAc). Ultra-conserved regions (UCRs) are a class non-coding sequences that are conserved in humans, mice and rats. More than 90% of UCRs are transcribed (T-UCRs) in normal tissues, and are altered at transcriptional level in tumorigenesis. To identify the T-UCR profiles that are dysregulated in Barretts mucosa transformation, microarray analysis was performed on a discovery set of 51 macro-dissected samples obtained from 14 long-segment BE patients. Results were validated in an independent series of esophageal biopsy/surgery specimens and in two murine models of Barretts esophagus (i.e. esophagogastric-duodenal anastomosis). Progression from normal to BE to adenocarcinoma was each associated with specific and mutually exclusive T-UCR signatures that included up-regulation of uc.58-, uc.202-, uc.207-, and uc.223- and down-regulation of uc.214+. A 9 T-UCR signature characterized BE versus Sq (with the down-regulation of uc.161-, uc.165-, and uc.327-, and the up-regulation of uc.153-, uc.158-, uc.206-, uc.274-, uc.472-, and uc.473-). Analogous BE-specific T-UCR profiles were shared by human and murine lesions. This study is the first demonstration of a role for T-UCRs in the transformation of Barretts mucosa

    Depth‐Distribution Patterns of Soil Organic Matter in the Tidal Marshes of the Venice Lagoon (Italy): Signatures of Depositional and Environmental Conditions

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    Salt marshes are depositional landforms lying at the upper margin of intertidal environments. They provide a diverse range of valuable ecosystem services and yet are exceptionally vulnerable to climate change and human pressure. Salt marshes are intrinsically dynamic environments, shaped by complex feedback between hydrodynamic, morphological, and biological processes. Soil Organic Matter (SOM) has a crucial role within salt marsh environments, as on the one hand, its accumulation contributes to the build-up of marsh elevation which is necessary for marshes to keep pace with sea-level rise, and on the other it supports the high carbon sink potential of wetlands. To better understand variations in SOM depth distribution and further comprehend SOM drivers, we analyzed soil organic content in 10 salt marshes of the microtidal Venice Lagoon from 60 sediment cores to the depth of 1 m, relating SOM spatial and vertical patterns to the temporal and spatial variability of depositional sub-environments recorded in the study deposits. Our results suggest that changes in the depositional environment are of primary importance in determining organic matter depth distribution and caution is needed in SOM prediction at unsampled soil depths. We observed relationships between SOM vertical patterns and factors such as autochthonous and allochthonous organic inputs, sediment properties, relative sea level rise, fluvial inputs and wave action. Our findings emphasize the considerable carbon storage potential of marshes in intertidal environments and provide a conceptual framework for understanding the dynamics of SOM and their drivers, which can inform and enhance coastal management strategies

    Modello di gestione dei prodotti medicinali di terapia cellulare avanzata CAR-T

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    Today, the medicine has largely abandoned the traditional chemical-physical characteristics of a simple molecule, sometimes assuming different forms as those of a cell: this requires a different management approach. The Chimeric Antigen Receptor T cells (CAR-T) are considered advanced therapy medicinal products and represent the last frontier of immunotherapy in oncology. The main objective of this work is the implementation of the CAR-T product management operational instruction by Hospital Pharmacy in collaboration with Transfusion Medicine. At the same time, a second objective has been defined: an analysis of the first case study of patients treated at the first Veneto’s Center with the aim of evaluating the clinical impact of this therapy. Materials and methods. For the realization of the main objective of this work the organizational, structural and technological characteristics of the cryobiological room of Hospital were analyzed and were used information programs such as the computerized system of prescription and administration and the warehouse management system. For the realization of the second objective, the information has been acquired through the NFS management system with the combined consultation of the AIFA monitoring register. Results. Starting from a pathway already defined for the management of an apheretic cell product, a pathway has been prepared that applies as a management model for the advanced cell therapy product obtained from lymphocytoapheresis or other cellular product autologous or allogeneic, genetically modified, classified as “drug” and administered to the patient. The data obtained from the analysis of the first infused patients shows that 38% went through complete remission of the disease while 31% died, showing a variability in the response to treatment. Conclusions. The increasing number of new cell-based therapies may require significant changes in the organization of Hospital Pharmacy, in terms of space and equipment. Faced with this therapeutic innovation, the hospital pharmacist is not excluded but is called to develop new skills and make its contribution with specific training as a health professional within multidisciplinary teams involved in the complete and safe management of medicinal products advanced therapy

    the isolpharm project a new isol production method of high specific activity beta emitting radionuclides as radiopharmaceutical precursors

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    The ISOLPHARM project explores the feasibility of exploiting an innovative technology to produce extremely high specific activity beta-emitting radionuclides as radiopharmaceutical precursors. This technique is expected to produce radiopharmaceuticals that are virtually mainly impossible to obtain in standard production facilities, at lower cost and with less environmental impact than traditional techniques. The groundbreaking ISOLPHARM method investigated in this project has been granted an international patent (INFN). As a component of the SPES (Selective Production of Exotic Species) project at the Istituto Nazionale di Fisica Nucleare–Laboratori Nazionali di Legnaro (INFN–LNL), a new facility will produce radioactive ion beams of neutron-rich nuclei with high purity and a mass range of 80–160 amu. The radioactive isotopes will result from nuclear reactions induced by accelerating 40 MeV protons in a cyclotron to collide on a target of UC[Formula: see text]. The uranium in the target material will be [Formula: see text]U, yielding radioactive isotopes that belong to elements with an atomic number between 28 and 57. Isotope separation on line (ISOL) is adopted in the ISOLPHARM project to obtain pure isobaric beams for radiopharmaceutical applications, with no isotopic contaminations in the beam or subsequent trapping substrate. Isobaric contaminations may potentially affect radiochemical and radionuclide purity, but proper methods to separate chemically different elements can be developed

    Improvement and extension of anti-EGFR targeting in breast cancer therapy by integration with the Avidin-Nucleic-Acid-Nano-Assemblies

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