Search results for " PATOLOGIA"
showing 10 items of 779 documents
Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma
2016
Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. We show that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, is expressed at low levels, possibly owing to epigenetic silencing. In LAC cells including the cancer stem cell compartment, we show that GLI1 is activated noncanonically by MAPK/ERK signaling. Different mechanisms can trigger the MAPK/ERK/GLI1 cascade including KRAS mutation and stimulation of NRP2 by VEGF produced by the cancer cells themselves in an autocrin…
PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer
2017
AbstractCombined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoprote…
Identification of plasma biomarkers for discrimination between tuberculosis infection/disease and pulmonary non tuberculosis disease.
2018
We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon γ Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells. The diagnostic accuracies of the markers detected were evaluated by ROC curve analysis and by the co…
Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms
2019
AbstractAneurysms and dissections affecting thoracic aorta are associated with smooth muscle cell (SMC) dysfunction. NO/cGMP signaling pathway in smooth muscle cells has been shown to be affected in sporadic thoracic aortic aneurysms. We analyzed the mRNA levels of PDE5, a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs, that regulates arterious vascular tone by lowering cGMP levels. We found that aortic tissue obtained from Marfan, tricuspid and bicuspid thoracic aneurysms expressed lower levels of PDE5 mRNA compared to control aortas. In particular, we found that affected aortas showed lower levels of all the PDE5A isoforms, compared to control aortas. Transfection of vascular SMC…
Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells
2018
Background It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with tumor cells and other stroma cells in the complex network of the tumor microenvironment. We characterized MSCs isolated and expanded from tumor tissues of pediatric patients diagnosed with neuroblastomas (NB-MSCs) to define interactions with the tumor microenvironment. Methods Specimens were obtained from 7 pediatric patients diagnosed with neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression of stemness and neural differentiation markers were evaluated. Moreover, the ability of cells to modulate the immune response, i.e. …
HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus.
2017
Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detecti…
The LuxR Regulators PcoR and RfiA Co-regulate Antimicrobial Peptide and Alginate Production in Pseudomonas corrugata
2018
Cyclic lipopeptides (CLPs) are considered as some of the most important secondary metabolites in different plant-associated bacteria, thanks to their antimicrobial, cytotoxic, and surfactant properties. In this study, our aim was to investigate the role of the Quorum Sensing (QS) system, PcoI/PcoR, and the LuxR-type transcriptional regulator RfiA in CLP production in the phytopatogenic bacterium, Pseudomonas corrugata based on our previous work where we reported that the pcoR and rfiA mutants were devoid of the CLPs cormycin and corpeptin production. Due to the close genetic link between the QS system and the RfiA (rfiA is co-transcribed with pcoI), it was difficult to ascertain the specifi…
Local adaptation in populations of Mycobacterium tuberculosis endemic to the Indian Ocean Rim
2021
24 páginas, 3 figuras, 1 tabla. The sequence data generated by this study has been deposited on SRA (https://www.ncbi.nlm.nih.gov/sra) under the accession number PRJNA670836. Extended data is available here: https://github.com/fmenardo/MTBC_L1_L3. DOI: https://doi.org/10.5281/zenodo.4609804 (Menardo, 2021).
Stem Cells and Other Emerging Agents as Innovative "Drugs" in Neurodegenerative Diseases: Benefits and Limitations.
2018
The brain has a limited process of repair/regeneration linked to the restricted and localized activity of neuronal stem cells. Consequently, it shows a reduced capacity to counteract the age-related loss of neural and glial cells and to repair the consequent injuries/lesions of nervous system. This progressively determines nervous dysfunction and onset/progression of neurodegenerative diseases, which represent a serious social (and economic) problem of our populations. Thus, the research of efficient treatments is encouraged. Stem cell therapy might represent a solution. Today, it, indeed, represents the object of intensive research with the hope of using it, in a near future, as effective …
Carnosine protects pancreatic beta cells and islets against oxidative stress damage
2018
Abstract Islet transplantation is a valid therapeutic option for type 1 diabetes treatment. However, in this procedure one of the major problems is the oxidative stress produced during pancreatic islet isolation. The aim of our study was to evaluate potential protective effects of L-carnosine and its isomer D-carnosine against oxidative stress. We evaluated the carnosine effect on cell growth, cell death, insulin production, and the main markers of oxidative stress in rat and murine stressed beta cell lines as well as in human pancreatic islets. Both isomers clearly inhibited hydrogen peroxide induced cytotoxicity, with a decrease in intracellular reactive oxygen and nitrogen species, preve…