Search results for "TYR"
showing 10 items of 2017 documents
Cirrhotic patients with minimal hepatic encephalopathy have increased capacity to eliminate superoxide and peroxynitrite in lymphocytes, associated w…
2018
Patients with minimal hepatic encephalopathy (MHE) show increased oxidative stress in blood. We aimed to assess whether MHE patients show alterations in different types of blood cells in (a) basal reactive oxygen and nitrogen species levels; (b) capacity to metabolise these species. To assess the mechanisms involved in the altered capacity to metabolise these species we also analysed: (c) peroxynitrite formation and d) peroxynitrite reaction with biological molecules. Levels of reactive oxygen and nitrogen species were measured by flow cytometry in blood cell populations from cirrhotic patients with and without MHE and controls, under basal conditions and after adding generators of superoxi…
Genetic susceptibility of increased intestinal permeability is associated with progressive liver disease and diabetes in patients with non-alcoholic …
2020
Abstract Background and aim Increased intestinal permeability plays a key role in the pathogenesis of fat deposition in the liver. The aim of our study was to assess whether a single nucleotide polymorphism of protein tyrosine phosphatase non-receptor type 2 (PTPN2) (rs2542151 T→G), involved in intestinal permeability, may be associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods and results We recruited a prospective cohort of NAFLD subjects and matched controls. Clinical data, PTPN2 genotype and laboratory data were collected for each patient. Results were stratified according to liver histology and diabetes. We enrolled 566 cases and 377 co…
Mer Tyrosine Kinase (MERTK) modulates liver fibrosis progression and hepatocellular carcinoma development.
2022
BackgroundMerTK is a tyrosine kinase receptor that belongs to the TAM (Tyro3/Axl/Mer) receptor family. It is involved in different processes including cellular proliferation/survival, cellular adhesion/migration, and release of the inflammatory/anti-inflammatory cytokines. Although it is reported that MERTK polymorphisms affect the severity of viral and metabolic liver diseases, being able to influence fibrosis progression and hepatocellular carcinoma development, the mechanisms remain unknown. Methods: using a microarray approach, we evaluated the liver expression of genes involved in fibrogenesis and hepatocarcinogenesis in patient with chronic hepatitis C (CHC), stratified for MERTK geno…
Optimizing systemic therapy for advanced hepatocellular carcinoma: the key role of liver function
2022
The number of effective systemic therapies for the treatment of advanced hepatocellular carcinoma (HCC) is rapidly increasing, and the advent of immunotherapy has changed the treatment paradigm for these patients, leading to significantly improved survival outcomes. However, many patients with HCC will continue to receive tyrosine kinase inhibitors, partly because of contraindications to immune checkpoint inhibitors. Currently, the best sequential first- and second-line systemic treatment remains elusive. Maintenance of optimal liver function is crucial, it is likely to impinge on temporary or permanent treatment discontinuation, and should also be considered when defining the treatment seq…
Stationary–mobile phase distribution coefficient for polystyrene standards
2002
The measured shifts of the retention volume V R of polystyrene (PS) towards lower values in benzene–methanol (Bz–MeOH), and towards higher values in butanone–heptane (But–Hep) are in agreement with our theoretical model, in which both MeOH and But are adsorbed on Lichrospher. This paved way for us to model the chromatographic stationary (s)-phase as MeOH and the mobile (m)-phase as Bz–MeOH, and to calculate the distribution coefficients for PS. For But–Hep, the s-phase has been modeled as But, and the m-phase as But–Hep. A linear relation for the experimental equilibrium distribution P sm of PS is shown between the s- and m- phases in Bz–MeOH and But–Hep vs. the logarithm of the molecular m…
Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study
2002
A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was prese…
Synthetic (glyco-)peptides of the homophilic recognition domain of E-cadherin lead to increased E-cadherin mRNA synthesis and are inductors of cell d…
2010
E-cadherin is one of the critical molecules involved in the metastatic process in many types of cancer. Once combined, E-cadherin exceeds the amount of membranous E-cadherin on the cellular surface by activation of intracellular signaling cascades. Studies on transformed keratinocytes of the HaCat cell line showed induction of differentiation by synthetical partial structures of the homophilic binding region of E-cadherin. The knowledge of effects in lung cancer cells is sparse. Therefore, the effects in primary lung cancer cell lines were investigated. Four primary lung cancer cell lines were incubated for 3, 6, 12, 15, 18, and 24h with synthetic partial structures (peptide and glycopeptid…
Driver mutations and differential sensitivity to targeted therapies: a new approach to the treatment of lung adenocarcinoma
2010
The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as "driver mutations". These are responsible for both the initiation and maintenance of the malignancy. The epidermal growth factor receptor (EGFR) pathway is the main regulator of cell function and cancer development. It has a widely defined role in the occurrence of driver mutations. Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma. In th…
The role of cMET in non-small cell lung cancer resistant to EGFR-Inhibitors: Did we really find the target?
2014
Abstract: The advent of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represented the most important innovation in NSCLC treatment over the last years. However, despite a great initial activity, secondary mutations in the same target, or different alterations in other molecular pathways, inevitably occur, leading to the emergence of acquired resistance, in median within the first year of treatment. In this scenario, the mesenchymal-epidermal transition (cMET) tyrosine kinase receptor and its natural ligand, the hepatocyte growth factor (HGF), seem to play an important role. Indeed either the overexpression or the amplification of cMET, as well as the overexpr…
UV resonance Raman spectroscopy: a process analytical tool for host cell DNA and RNA dynamics in mammalian cell lines
2014
BACKGROUND Recent advances in Raman spectroscopy have resulted in the development of rapid, in situ Raman probes that can identify and allow the assessment of the quality of complex constituents in mammalian cell culture. One specific Raman technique, UV resonance Raman (UVRR) spectroscopy, has potential as a probe for residual cellular DNA and RNA in mammalian cell culture medium. RESULTS Variations in DNA and RNA UVRR spectral profiles of medium-cellular footprint samples were identified and related to time of harvest and increased cell lysis that is associated with a loss in cell viability. Increased DNA and RNA were also observed in the cell culture supernatant in response to sodium but…