Search results for "testi"
showing 10 items of 4607 documents
Gut Microbiota Condition the Therapeutic Efficacy of Trastuzumab in HER2-Positive Breast Cancer.
2021
Abstract Emerging evidence indicates that gut microbiota affect the response to anticancer therapies by modulating the host immune system. In this study, we investigated the impact of gut microbiota on immune-mediated trastuzumab antitumor efficacy in preclinical models of HER2-positive breast cancer and in 24 patients with primary HER2-positive breast cancer undergoing trastuzumab-containing neoadjuvant treatment. In mice, the antitumor activity of trastuzumab was impaired by antibiotic administration or fecal microbiota transplantation from antibiotic-treated donors. Modulation of the intestinal microbiota was reflected in tumors by impaired recruitment of CD4+ T cells and granzyme B–posi…
Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver
2021
Metastasis is facilitated by the formation of a "premetastatic niche," which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC. We report that tumor-resident bacteria Escherichia coli disrupt the gut vascular barrier (GVB), an anatomical structure controlling bacterial dissemination along the gut-liver axis, depending on the virulence regulator VirF. Upon GVB impairment, bacteria disseminate to the liver, boost the formation of a premetastatic niche, and favor the recruitment of metastatic cells. In training and validation cohorts of C…
Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts
2020
International audience; Treatment with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1) can generate durable responses in various cancer types, but only in a subset of patients. The use of predictive biomarkers for response to PD-1/PD-L1 inhibitors is critical for patient selection. Expression of PD-L1 has demonstrated utility in patient selection. Tumour mutational burden (TMB) is an emerging biomarker for response to PD-1/PD-L1 inhibitors. The evaluation of this biomarker is based on the hypothesis that a high number of mutations in somatic exonic regions will lead to an increase in neoantigen production, which could then be recognised by…
Breast Cancer Organoids Model Patient-Specific Response to Drug Treatment
2020
Tumor organoids are tridimensional cell culture systems that are generated in vitro from surgically resected patients&rsquo
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…
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…
Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis
2019
Summary MyD88, an adaptor molecule downstream of innate pathways, plays a significant tumor-promoting role in sporadic intestinal carcinogenesis of the Apcmin/+ model, which carries a mutation in the Apc gene. Here, we show that deletion of MyD88 in intestinal mesenchymal cells (IMCs) significantly reduces tumorigenesis in this model. This phenotype is associated with decreased epithelial cell proliferation, altered inflammatory and tumorigenic immune cell infiltration, and modified gene expression similar to complete MyD88 knockout mice. Genetic deletion of TLR4, but not interleukin-1 receptor (IL-1R), in IMCs led to altered molecular profiles and reduction of intestinal tumors similar to …
Tight Junctions as a Key for Pathogens Invasion in Intestinal Epithelial Cells
2021
Tight junctions play a major role in maintaining the integrity and impermeability of the intestinal barrier. As such, they act as an ideal target for pathogens to promote their translocation through the intestinal mucosa and invade their host. Different strategies are used by pathogens, aimed at directly destabilizing the junctional network or modulating the different signaling pathways involved in the modulation of these junctions. After a brief presentation of the organization and modulation of tight junctions, we provide the state of the art of the molecular mechanisms leading to permeability breakdown of the gut barrier as a consequence of tight junctions’ attack by pathogens, including…
Transcytosis of Bacillus subtilis extracellular vesicles through an in vitro intestinal epithelial cell model
2020
Bacterial EVs have been related to inter-kingdom communication between probiotic/pathogenic bacteria and their hosts. Our aim was to investigate the transcytosis process of B. subtilis EVs using an in vitro intestinal epithelial cell model. In this study, using Confocal Laser Scanning Microscopy, we report that uptake and internalization of CFSE-labeled B. subtilis EVs (115 nm ± 27 nm) by Caco-2 cells are time-dependent. To study the transcytosis process we used a transwell system and EVs were quantified in the lower chamber by Fluorescence and Nanoparticle Tracking Analysis measurements. Intact EVs are transported across a polarized cell monolayer at 60–120 min and increased after 240 min …