Search results for "22"
showing 10 items of 13984 documents
The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system
2019
International audience; Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-l…
Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma.
2018
Patient-derived xenografts (PDX) and the Avatar, a single PDX mirroring an individual patient, are emerging tools in preclinical cancer research. However, the consequences of intratumor heterogeneity for PDX modeling of biomarkers, target identification, and treatment decisions remain under-explored. In this study, we undertook serial passaging and comprehensive molecular analysis of neuroblastoma orthotopic PDXs, which revealed strong intrinsic genetic, transcriptional, and phenotypic stability for more than 2 years. The PDXs showed preserved neuroblastoma-associated gene signatures that correlated with poor clinical outcome in a large cohort of patients with neuroblastoma. Furthermore, we…
Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells
2018
Background It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with tumor cells and other stroma cells in the complex network of the tumor microenvironment. We characterized MSCs isolated and expanded from tumor tissues of pediatric patients diagnosed with neuroblastomas (NB-MSCs) to define interactions with the tumor microenvironment. Methods Specimens were obtained from 7 pediatric patients diagnosed with neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression of stemness and neural differentiation markers were evaluated. Moreover, the ability of cells to modulate the immune response, i.e. …
DNA methylation changes and somatic mutations as tumorigenic events in Lynch syndrome-associated adenomas retaining mismatch repair protein expression
2018
Background: DNA mismatch repair (MMR) defects are a major factor in colorectal tumorigenesis in Lynch syndrome (LS) and 15% of sporadic cases. Some adenomas from carriers of inherited MMR gene mutations have intact MMR protein expression implying other mechanisms accelerating tumorigenesis. We determined roles of DNA methylation changes and somatic mutations in cancer-associated genes as tumorigenic events in LS-associated colorectal adenomas with intact MMR. Methods: We investigated 122 archival colorectal specimens of normal mucosae, adenomas and carcinomas from 57 LS patients. MMR-deficient (MMR-D, n 49) and MMR-proficient (MMR-P, n 18) adenomas were of particular interest and were inter…
DRH1 - a novel blood-based HPV tumour marker.
2020
Abstract Background To date, no studies have successfully shown that a highly specific, blood-based tumour marker to detect clinically relevant HPV-induced disease could be used for screening, monitoring therapy response or early detection of recurrence. This study aims to assess the clinical performance of a newly developed HPV16-L1 DRH1 epitope-specific serological assay. Methods In a multi-centre study sera of 1486 patients (301 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, 12 HIV+ anal cancer patients, 80 HIV-positive patients, 29 Gardasil-9-vaccinees, 1064 healthy controls) were tested for human HPV16-L1 DRH1 antibodies. Analytical specificity was determined using WHO referen…
Longitudinal Analysis of Serum Autoantibody-Reactivities in Patients with Primary Open Angle Glaucoma and Optic Disc Hemorrhage.
2015
Background The aim of our current investigation was to analyze the autoantibody-reactivities of primary open angle glaucoma patients with optic disc hemorrhage as possibly correlated to disease progression by means of a protein microarray approach. Methods Sera of patients with primary open angle glaucoma and optic disc hemorrhage (n = 16) were collected directly after study inclusion (0 weeks) and after 2 weeks, 4 weeks and 12 weeks. As a control group patients with primary open angle glaucoma (n = 18) were used (0 weeks and 12 weeks). Microarrays were incubated and occurring antibody-antigen-reactions were visualized with fluorescence labeled anti-human-IgG secondary antibodies. To detect…
The clinical relevance of adiposity when assessing muscle health in men treated with androgen deprivation for prostate cancer
2019
Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) may prospectively decrease absolute lean mass (LM) and increase absolute fat mass (FM). Given that estimates of LM by dual‐energy X‐ray absorptiometry may be overestimated in obese people, this study examined the influence of adiposity on muscle health in men treated with ADT for PCa. Methods: This cross‐sectional study examined the influence of adiposity on total and appendicular LM (ALM), muscle cross‐sectional (CSA), and muscle strength in 70 men treated with ADT [mean (standard deviation) age, 71 (6) years] for PCa compared with age‐matched PCa (n = 52) and healthy controls (n = 70). Total body LM, FM and ALM, and …
Objective Assessment of Nuclear and Cortical Cataracts through Scheimpflug Images: Agreement with the LOCS III Scale.
2016
Purpose To assess nuclear and cortical opacities through the objective analysis of Scheimpflug images, and to check the correlation with the Lens Opacity Classification System III (LOCS III). Methods Nuclear and cortical opacities were graded according to the LOCS III rules after pupil dilation. The maximum and average pixel intensity values along an elliptical mask within the lens nucleus were taken to analyse nuclear cataracts. A new metric based on the percentage of opaque pixels within a region of interest was used to analyse cortical cataracts. The percentage of opaque pixels was also calculated for half, third and quarter areas from the region of interest’s periphery. Results The maxi…
Epidemiology of rare cancers and inequalities in oncologic outcomes
2019
Rare cancers epidemiology is better known compared to the other rare diseases. Thanks to the long history of the European population-based cancer registries and to the EUROCARE huge database, the burden of rare cancers has been estimated the European (EU28) population. A considerable fraction of all cancers is represented by rare cancers (24%). They are a heterogeneous group of diseases, but they share similar problems: uncertainty of diagnosis, lack of therapies, poor research opportunities, difficulties in clinical trials, lack of expertise and of centres of reference. This paper analyses the major epidemiological indicators of frequency (incidence and prevalence) and outcome (5-year surv…
Mast cells are associated with the onset and progression of celiac disease
2017
Background Celiac disease (CD) is an immune-mediated disorder characterized by an accumulation of immune cells in the duodenal mucosa as a consequence of both adaptive and innate immune responses to undigested gliadin peptides. Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa. Although MCs have previously been associated with CD, functional studies have never been performed. Objective We aimed at evaluating the role of MCs in the pathogenesis of CD. Methods Intestinal biopsy specimens of patients with CD were scored according to the Marsh classification and characterized for leukocyte infiltration a…