Search results for "Nap"

Immune checkpoint inhibitors in lung cancer: the holy grail has not yet been found…

2017

Lung cancer is rich in molecular complexities and driven by different abnormal molecular pathways. Personalised medicine has begun to bring new hope for the treatment of patients with lung cancer, especially non-small cell lung cancer (NSCLC). The development of molecularly targeted therapy (small molecules and monoclonal antibodies) has significantly improved outcomes in the metastatic setting for patients with NSCLC whose tumours harbour activated oncogenes such as epidermal growth factor receptor (EGFR) and translocated genes like anaplastic lymphoma kinase (ALK). In addition, immune checkpoint inhibitors have also dramatically changed the therapeutic landscape of NSCLC. In particular, m…

Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC

2017

[EN] Background Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods Clinically annotated, resected stage I¿III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is¿>1% for most of the ~150 (13 genes) mutations covered in the multiplex test.…

A narrative review of MET inhibitors in non-small cell lung cancer with MET exon 14 skipping mutations

2021

Treatment of advanced non-small cell lung cancer (NSCLC) has radically improved in the last years due to development and clinical approval of highly effective agents including immune checkpoint inhibitors (ICIs) and oncogene-directed therapies. Molecular profiling of lung cancer samples for activated oncogenes, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and BRAF, is routinely performed to select the most appropriate up-front treatment. However, the identification of new therapeutic targets remains a high priority. Recently, MET exon 14 skipping mutations have emerged as novel actionable oncogenic alterations in NSCLC, sensiti…

IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells

2016

Background Cutaneous exposure to food allergens predisposes to food allergy, which is commonly associated with atopic dermatitis (AD). Levels of the epithelial cytokine IL-33 are increased in skin lesions and serum of patients with AD. Mast cells (MCs) play a critical role in food-induced anaphylaxis and express the IL-33 receptor ST2. The role of IL-33 in patients with MC-dependent food anaphylaxis is unknown. Objective We sought to determine the role and mechanism of action of IL-33 in patients with food-induced anaphylaxis in a model of IgE-dependent food anaphylaxis elicited by oral challenge of epicutaneously sensitized mice. Methods Wild-type, ST2-deficient, and MC-deficient Kit W-sh/…

Subchronic administration of auranofin reduced amyloid-β plaque pathology in a transgenic APPNL-G-F/NL-G-F mouse model

2020

Abstract Alzheimer’s disease (AD) is the most common cause of dementia. Neuropathological processes, including the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles, and neuroinflammation, lead to cognitive impairment at middle and eventually later stages of AD progression. Over the last decade, focused efforts have explored repurposed drug approaches for AD pathophysiological mechanisms. Recently, auranofin, an anti-inflammatory drug, was shown to have therapeutic potential in a number of diseases in addition to rheumatoid arthritis. Surprisingly, no data regarding the effects of auranofin on cognitive deficits in AD mice or the influence of auranofin on Aβ pathology and n…

Contribution of cholesterol and oxysterols to the pathophysiology of Parkinson's disease

2016

International audience; Neurodegenerative diseases are a major public health issue worldwide. Some countries, including France, have engaged in research into the causes of Parkinson's disease, Alzheimer's disease, and multiple sclerosis and the management of these patients. It should lead to a better understanding of the mechanisms leading to these diseases including the possible involvement of lipids in their pathogenesis. Parkinson's disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein (Lewy bodies). Several in vivo studies have shown a relationship between the lipid profile [chole…

Actinin-4 splice variant - a complementary diagnostic and prognostic marker of pancreatic neuroendocrine neoplasms.

2019

Introduction: For pathological diagnosis of pancreatic neuroendocrine neoplasms (pNENs) the routinely used immunohistochemical markers are chromogranin A (CgA) and synaptophysin (Syn). Their ability as prognostic markers is not well established. A splice variant of actinin-4 (Actn-4sv) was recently found to be an excellent biomarker of neuroendocrine neoplasms of the lung. We aimed to investigate the expression of Actn-4sv in pNENs and evaluate its quality as a biomarker of pNENs. Methods: Paraffin-embedded and frozen tissues specimens from 122 pNENs were analyzed. Western blots were performed to prove and compare the relative amount of Actn-4sv expression in pNENs tissue homogenates. For c…

Cytotoxicity and mode of action of a naturally occurring naphthoquinone, 2-acetyl-7-methoxynaphtho[2,3-b]furan-4,9-quinone towards multi-factorial dr…

2017

Abstract Introduction Malignacies are still a major public concern worldwide and despite the intensive search of new chemotherapeutic agents, treatment still remains a challenging issue. The present study was designed to evaluate the cytotoxicity of 2-acetyl-7-methoxynaphtho[2,3-b]furan-4,9-quinone (AMNQ) isolated from the bark of Milletia versicolor towards a panel of drug-sensitive and multidrug-resistant (MDR) cancer cell lines. Methods The resazurin reduction assay was used to evaluate the cytotoxicity of AMNQ against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species were all analyze…

Cocaine-induced changes in CX3CL1 and inflammatory signaling pathways in the hippocampus: Association with IL1β

2020

Cocaine induces neuroinflammatory response and interleukin-1 beta (IL1β) is suggested a final effector for many cocaine-induced inflammatory signals. Recently, the chemokine fractalkine (CX3CL1) has been reported to regulate hippocampus-dependent neuroinflammation and synaptic plasticity via CX3C-receptor 1 (CX3CR1), but little is known about the impact of cocaine. This study is mainly focused on the characterization of CX3CL1, IL1β and relevant inflammatory signal transduction pathways in the hippocampus in acute and repeated cocaine-treated male mice. Complementarily, the rewarding properties of cocaine were also assessed in Cx3cr1-knockout (KO) mice using a conditioned place preference (…

2018

Haplotypes of the Gabra2 gene encoding the α2-subunit of the GABAA receptor (GABAAR) are associated with drug abuse, suggesting that α2-GABAARs may play an important role in the circuitry underlying drug misuse. The genetic association of Gabra2 haplotypes with cocaine addiction appears to be evident primarily in individuals who had experienced childhood trauma. Given this association of childhood trauma, cocaine abuse and the Gabra2 haplotypes, we have explored in a mouse model of early life adversity (ELA) whether such events influence the behavioral effects of cocaine and if, as suggested by the human studies, α2-GABAARs in the nucleus accumbens (NAc) are involved in these perturbed beha…