Search results for " Targeted therapy"
showing 10 items of 198 documents
Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours
2019
BACKGROUND: Interferon-induced expression of programmed cell death ligands (PD-L1/PD-L2) may sustain tumour immuneevasion. Patients featuring MET amplification, a genetic lesion driving transformation, may benefit from anti-MET treatment. We explored if MET-targeted therapy interferes with Interferon-gamma modulation of PD-L1/PD-L2 in MET-amplified tumours.METHODS: PD-L1/PD-L2 expression and signalling pathways downstream of MET or Interferon-gamma were analysed in MET-amplified tumour cell lines and in patient-derived tumour organoids, in basal condition, upon Interferon-gamma stimulation, and after anti-MET therapy.RESULTS: PD-L1 and PD-L2 were upregulated in MET-amplified tumour cells up…
Neutrophil Extracellular Traps as a Drug Target to Counteract Chronic and Acute Inflammation
2019
Neutrophil extracellular traps (NET), extruded decondensated chromatin entangled with neutrophil proteases, have been first identified in neutrophils stimulated with bacteria or phorbol myristate acetate (PMA) via activation of NADPH oxidase and the generation of reactive oxygen species. Although the first findings demonstrated the beneficial role of NET formation by trapping the bacteria and limiting their dissemination, numerous studies in the recent decade revealed the multifunctional aspects of NET formation which manifests itself not only in the context of anti-microbial effect but also as a pathological trigger. Uncontrolled and exaggerated NET formation or inability to digest and rem…
Multi-output Model with Box-Jenkins Operators of Quadratic Indices for Prediction of Malaria and Cancer Inhibitors Targeting Ubiquitin- Proteasome Pa…
2016
The ubiquitin-proteasome pathway (UPP) is the primary degradation system of short-lived regulatory proteins. Cellular processes such as the cell cycle, signal transduction, gene expression, DNA repair and apoptosis are regulated by this UPP and dysfunctions in this system have important implications in the development of cancer, neurodegenerative, cardiac and other human pathologies. UPP seems also to be very important in the function of eukaryote cells of the human parasites like Plasmodium falciparum, the causal agent of the neglected disease Malaria. Hence, the UPP could be considered as an attractive target for the development of compounds with Anti-Malarial or Anti-cancer properties. R…
An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.
2016
Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub…
Translational Approaches In Cardiovascular Diseases by Omics.
2017
Cardiovascular diseases are among the leading causes of morbidity and mortality. Despite scientific and technical progress in risk prediction, diagnostics, prognostication and therapy of cardiovascular pathologies, new biomarkers and therapeutic targets remain the subject of intense research to reduce the burden of these diseases. High throughput analyses, termed "omics", are a promising avenue of research. These recently developed technical fields have revolutionized biological and medical research in a very short time. By their interdisciplinary nature, these new methods have already provided a wide vision of cell and tissue pathways and functions. Here, we review how these methods can he…
Extracellular Heat Shock Proteins as Therapeutic Targets and Biomarkers in Fibrosing Interstitial Lung Diseases.
2021
Interstitial lung diseases (ILDs) include a large number of diseases and causes with variable outcomes often associated with progressive fibrosis. Although each of the individual fibrosing ILDs are rare, collectively, they affect a considerable number of patients, representing a significant burden of disease. Idiopathic pulmonary fibrosis (IPF) is the typical chronic fibrosing ILD associated with progressive decline in lung. Other fibrosing ILDs are often associated with connective tissues diseases, including rheumatoid arthritis-ILD (RA-ILD) and systemic sclerosis-associated ILD (SSc-ILD), or environmental/drug exposure. Given the vast number of progressive fibrosing ILDs and the dispariti…
Novel therapeutical approaches to managing atherosclerotic risk
2021
Atherosclerosis is a multifactorial vascular disease that leads to inflammation and stiffening of the arteries and decreases their elasticity due to the accumulation of calcium, small dense Low Density Lipoproteins (sdLDL), inflammatory cells, and fibrotic material. A review of studies pertaining to cardiometabolic risk factors, lipids alterations, hypolipidemic agents, nutraceuticals, hypoglycaemic drugs, atherosclerosis, endothelial dysfunction, and inflammation was performed. There are several therapeutic strategies including Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) inhibitors, inclisiran, bempedoic acid, Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RAs), and nutraceuticals t…
Unmet needs and challenges in gastric cancer: The way forward
2014
AbstractAlthough the incidence of gastric cancer has fallen steadily in developed countries over the past 50years, outcomes in Western countries remain poor, primarily due to the advanced stage of the disease at presentation. While earlier diagnosis would help to improve outcomes for patients with gastric cancer, better understanding of the biology of the disease is also needed, along with advances in therapy. Indeed, progress in the treatment of gastric cancer has been limited, mainly because of its genetic complexity and heterogeneity. As a result, there is an urgent need to apply precision medicine to the management of the disease in order to ensure that individuals receive the most appr…
QSAR multi-target in drug discovery: a review.
2013
The main purpose of the present review is to summarize the most significant works up to date in the field of multi-target QSAR (mt-QSAR), in order to emphasize the importance that this technique has acquired over the last decade. Unlike traditional QSAR techniques, mt-QSAR permits to calculate the probability of activity of a given compound against different biological or pharmacological targets. In simple terms, a single equation for multiple outputs. To emphasize more the importance of the mt-QSAR in the field of drug discovery, we also present a novel mt-QSAR model, made on purpose by our research group, for the prediction of the susceptibility of Gram + and Gram - anaerobic bacteria.
Caveolin-1, breast cancer and ionizing radiation
2015
Breast cancer (BC) recovery has increased in recent years thanks to efforts of Omics-based research in this field. However, despite the important results obtained, BC remains a complex multifactorial pathology that is difficult to treat appropriately. Caveolin-1 (CAV1), the basic constituent protein of specialized plasma membrane invaginations called caveolae, is emerging as a potential therapeutic biomarker in BC. This factor may modulate BC response to chemotherapy and radiation therapy. In addition, recent reports describe the key role of CAV1 during cell response to oxidative stress. The aim of the present review was to describe the biological roles of CAV1 in BC considering its contras…