Search results for "STING"
showing 10 items of 3756 documents
Rationale for stimulator of interferon genes-targeted cancer immunotherapy
2017
International audience; The efficacy of checkpoint inhibitor therapy illustrates that cancer immunotherapy, which aims to foster the host immune response against cancer to achieve durable anticancer responses, can be successfully implemented in a routine clinical practice. However, a substantial proportion of patients does not benefit from this treatment, underscoring the need to identify alternative strategies to defeat cancer. Despite the demonstration in the 1990's that the detection of danger signals, including the nucleic acids DNA and RNA, by dendritic cells (DCs) in a cancer setting is essential for eliciting host defence, the molecular sensors responsible for recognising these dange…
An International Proficiency Study with the Tumor Marker CA 125
1990
A strict and adequate quality assurance program is the only real guarantee of the reliability of laboratory test results. Such proficiency testing was carried out for the CA 125 test system in five university laboratories over a period of three years (1984 - 1987) using five different reference materials (BIOREF, FRG). A concentration-dependent performance profile could thus be established evaluating a total of 301 assays. Intra-assay precision of the test ranged between 4.8 and 11.5%, and interassay precision between 13.6 and 19.1%. Laboratory specific average values of the individual reference materials ranged between 26 and 32 U/ml for reference 1, 51 and 59 U/ml for reference 2, 109 an…
Hereditary breast and ovarian cancer in families from southern Italy (Sicily)—Prevalence and geographic distribution of pathogenic variants in BRCA1/…
2020
Recent advances in the detection of germline pathogenic variants (PVs) in BRCA1/2 genes have allowed a deeper understanding of the BRCA-related cancer risk. Several studies showed a significant heterogeneity in the prevalence of PVs across different populations. Because little is known about this in the Sicilian population, our study was aimed at investigating the prevalence and geographic distribution of inherited BRCA1/2 PVs in families from this specific geographical area of Southern Italy. We retrospectively collected and analyzed all clinical information of 1346 hereditary breast and/or ovarian cancer patients genetically tested for germline BRCA1/2 PVs at University Hospital Policlini…
Moderate Exercise Improves Experimental Cancer Cachexia by Modulating the Redox Homeostasis
2019
Cachexia is a debilitating syndrome that complicates the management of cancer patients. Muscle wasting, one of the main features of cachexia, is associated with hyper-activation of protein degradative pathways and altered mitochondrial function that could both result from impaired redox homeostasis. This study aimed to investigate the contribution of oxidative stress to cancer-induced cachexia in the presence or in the absence of moderate exercise training. Mice bearing the colon C26 carcinoma, either sedentary or exercised, were used. The former showed muscle wasting and redox imbalance, with the activation of an antioxidant response and with upregulation of markers of proteasome-dependent…
Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)
2017
Background and aims: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). Methods: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationw…
Signalling strength determines proapoptotic functions of STING
2017
Mammalian cells use cytosolic nucleic acid receptors to detect pathogens and other stress signals. In innate immune cells the presence of cytosolic DNA is sensed by the cGAS–STING signalling pathway, which initiates a gene expression programme linked to cellular activation and cytokine production. Whether the outcome of the STING response varies between distinct cell types remains largely unknown. Here we show that T cells exhibit an intensified STING response, which leads to the expression of a distinct set of genes and results in the induction of apoptosis. Of note, this proapoptotic STING response is still functional in cancerous T cells and delivery of small molecule STING agonists prev…
Disease–Genes Must Guide Data Source Integration in the Gene Prioritization Process
2019
One of the main issues in detecting the genes involved in the etiology of genetic human diseases is the integration of different types of available functional relationships between genes. Numerous approaches exploited the complementary evidence coded in heterogeneous sources of data to prioritize disease-genes, such as functional profiles or expression quantitative trait loci, but none of them to our knowledge posed the scarcity of known disease-genes as a feature of their integration methodology. Nevertheless, in contexts where data are unbalanced, that is, where one class is largely under-represented, imbalance-unaware approaches may suffer a strong decrease in performance. We claim that …
High fat diets for weight loss among subjects with elevated fasting glucose levels: The PREDIMED study
2020
Abstract Aim We studied fasting plasma glucose (FPG) as a determinant of weight change on high-fat diets in the PREDIMED trial. Methods A total of 3,622 participants were randomized to receive one of two Mediterranean diets (n = 2,616) or a control diet (n = 1,006) for 5 years and had complete data for baseline FPG and body-weight development. Weight change by pre-treatment FPG categories ( Results The two Mediterranean diets contained 41.5 E% fat, 16.5 E% protein, and 40 E% carbohydrate whereas the control diet contained 37.8 E% fat, 16.8 E% protein and 43.2 E% carbohydrate. In the Mediterranean diet groups, participants with FPG≥115 lost 1.04 kg (95% CI 0.68; 1.41, n = 1115) whereas parti…
Reducing sample size in experiments with animals: historical controls and related strategies
2015
Reducing the number of animal subjects used in biomedical experiments is desirable for ethical and practical reasons. Previous reviews of the benefits of reducing sample sizes have focused on improving experimental designs and methods of statistical analysis, but reducing the size of control groups has been considered rarely. We discuss how the number of current control animals can be reduced, without loss of statistical power, by incorporating information from historical controls, i.e. subjects used as controls in similar previous experiments. Using example data from published reports, we describe how to incorporate information from historical controls under a range of assumptions that mig…
Network-Wide Adaptive Burst Detection Depicts Neuronal Activity with Improved Accuracy
2017
Neuronal networks are often characterized by their spiking and bursting statistics. Previously, we introducedan adaptive burst analysis methodwhich enhances the analysis power for neuronal networks with highly varying firing dynamics. The adaptation is based on single channels analyzing each element of a network separately. Such kind of analysis was adequate for the assessment of local behavior, where the analysis focuses on the neuronal activity in the vicinity of a single electrode. However, the assessment of the whole network may be hampered, if parts of the network are analyzed using different rules. Here, we test how using multiple channels and measurement time points affect adaptive b…