Search results for " patologia"
showing 10 items of 779 documents
Cancer stem cell-based models of colorectal cancer reveal molecular determinants of therapy resistance
2016
Abstract Colorectal cancer (CRC) therapy mainly relies on the use of conventional chemotherapeutic drugs combined, in a subset of patients, with epidermal growth factor receptor [EGFR]-targeting agents. Although CRC is considered a prototype of a cancer stem cell (CSC)-driven tumor, the effects of both conventional and targeted therapies on the CSC compartment are largely unknown. We have optimized a protocol for colorectal CSC isolation that allowed us to obtain CSC-enriched cultures from primary tumor specimens, with high efficiency. CSC isolation was followed by in vitro and in vivo validation, genetic characterization, and drug sensitivity analysis, thus generating panels of CSC lines w…
PI3K-driven HER2 expression is a potential therapeutic target in colorectal cancer stem cells
2020
ObjectiveCancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy.DesignA collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional…
SPARC regulation of PMN clearance protects from pristane-induced lupus and rheumatoid arthritis
2021
Summary The secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein with unexpected immunosuppressive function in myeloid cells. We investigated the role of SPARC in autoimmunity using the pristane-induced model of lupus that, in mice, mimics human systemic lupus erythematosus (SLE). Sparc−/− mice developed earlier and more severe renal disease, multi-organ parenchymal damage, and arthritis than the wild-type counterpart. Sparc+/- heterozygous mice showed an intermediate phenotype suggesting Sparc gene dosage in autoimmune-related events. Mechanistically, reduced Sparc expression in neutrophils blocks their clearance by macrophages, through defective delivery of don'…
Vascular ageing and endothelial cell senescence: Molecular mechanisms of physiology and diseases
2016
Ageing leads to a progressive deterioration of structure and function of all organs over the time. During this process endothelial cells undergo senescence and manifest significant changes in their properties, resulting in impairment of the vascular functionality and neo-angiogenic capability. This ageing-dependent impairment of endothelial functions is considered a key factor contributing to vascular dysfunctions, which is responsible of several age-related diseases of the vascular system and other organs. Several mechanisms have been described to control ageing-related endothelial cell senescence including microRNAs, mitochondrial dysfunction and micro environmental stressors, such as hyp…
Diagnostic and Prognostic Relevance of Red Blood Cell Distribution Width for Vascular Aging and Cardiovascular Diseases.
2019
Evidence suggests association of red blood cell distribution width (RDW) with cardiovascular diseases (CVDs). On the contrary, we underline that the sole RDW values cannot represent a valid CVD biomarker. High RDW values are expression of biological effects of a lot of both endogenous and exogenous factors (i.e., age, sex, genetic background, inflammation, hormones, drugs, diet, exercise, hematological analyzers, and ranges of values), modulating the biology and physiology of erythrocytes. Thus, the singular monitoring of RDW cannot be used to predict cardiovascular disorders. Accordingly, we have reviewed the evidence for potential relationship of RDW values with alterations in the cardiov…
Mediterranean nutraceutical foods: Strategy to improve vascular ageing.
2015
Ageing is characterized by a decline in all systemic functions. A greater susceptibility to apoptosis and senescence may contribute to proliferative and functional impairment of endothelial progenitor cells. They play an important role in neo-angiogenesis and endothelial repair. Vascular ageing is associated with changes in the structure and functions of vessels' wall. There are many possible causes of this damage. For sure, inflammation and oxidative stress play a fundamental role in the pathogenesis of endothelial dysfunction, commonly attributed to a reduced availability of nitric oxide. Inflammageing, the chronic low-grade inflammation that characterizes elderly people, aggravates vascu…
Ageing: from inflammation to cancer.
2018
Abstract Ageing is the major risk factor for cancer development. Hallmark of the ageing process is represented by inflammaging, which is a chronic and systemic low-grade inflammatory process. Inflammation is also a hallmark of cancer and is widely recognized to influence all cancer stages from cell transformation to metastasis. Therefore, inflammaging may represent the biological phenomena able to couple ageing process with cancer development. Here we review the molecular and cellular pathway involved in age-related chronic inflammation along with its potential triggers and their connection with cancer development.
Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience
2020
The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, mye…
HLA and killer cell immunoglobulin-like receptor (KIRs) genotyping in patients with acute viral encephalitis
2018
// Antonino Tuttolomondo 1 , Claudia Colomba 2 , Danilo Di Bona 6 , Alessandra Casuccio 4 , Domenico Di Raimondo 1 , Giuseppe Clemente 1 , Valentina Arnao 5 , Rosaria Pecoraro 1 , Paolo Ragonese 5 , Anna Aiello 3 , Giulia Accardi 3 , Rosario Maugeri 5 , Carlo Maida 1 , Irene Simonetta 1 , Vittoriano Della Corte 1 , Domenico Gerardo Iacopino 5 , Calogero Caruso 3 , Antonio Cascio 2 and Antonio Pinto 1 on behalf of KIRIIND (KIR Infectious and Inflammatory Diseases) Collaborative Group 1 U.O.C di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Universita degli Studi di Palermo, Palermo, Italy 2 U.O.C di Malattie Infettive, Dipartiment…
Th17 skewing in the GALT of a Crohn disease patient upon Lactobacillus rhamnosus GG consumption.
2015
We wish to report on a recent observation we made and that might represent a useful hint for the employment of the so called probiotics in the management of some pathological immune reactions of the gut. By analyzing GALT-associated T cells upon consumption of L. rhamnosus-GG, we obtained some hints that probiotics might have locoregional immunological effects mainly when administered in patients with IBDs rather than in individuals with non-inflamed gut mucosa.