Search results for "MUC1"
showing 10 items of 80 documents
Antibody Induction Directed against the Tumor-Associated MUC4 Glycoprotein
2015
Mucin glycoproteins are important diagnostic and therapeutic targets for cancer treatment. Although several strategies have been developed to explore anti-tumor vaccines based on MUC1 glycopeptides, only few studies have focused on vaccines directed against the tumor-associated MUC4 glycoprotein. MUC4 is an important tumor marker overexpressed in lung cancer and uniquely expressed in pancreatic ductual adenocarcinoma. The aberrant glycosylation of MUC4 in tumor cells results in an exposure of its peptide backbone and the formation of tumor-associated glycopeptide antigens. Due to the low immunogenicity of these endogenous structures, their conjugation with immune stimulating peptide or prot…
Microarray analysis of antibodies induced with synthetic antitumor vaccines : specificity against diverse mucin core structures
2017
Glycoprotein research is pivotal for vaccine development and biomarker discovery. Many successful methodologies for reliably increasing the antigenicity toward tumor-associated glycopeptide structures have been reported. Deeper insights into the quality and specificity of the raised polyclonal, humoral reactions are often not addressed, despite the fact that an immunological memory, which produces antibodies with cross-reactivity to epitopes exposed on healthy cells, may cause autoimmune diseases. In the current work, three MUC1 antitumor vaccine candidates conjugated with different immune stimulants are evaluated immunologically. For assessment of the influence of the immune stimulant on a…
Morphogenetic (Mucin Expression) as Well as Potential Anti-Corona Viral Activity of the Marine Secondary Metabolite Polyphosphate on A549 Cells
2020
The mucus layer of the nasopharynx and bronchial epithelium has a barrier function against inhaled pathogens such as the coronavirus SARS-CoV-2. We recently found that inorganic polyphosphate (polyP), a physiological, metabolic energy (ATP)-providing polymer released from blood platelets, blocks the binding of the receptor binding domain (RBD) to the cellular ACE2 receptor in vitro. PolyP is a marine natural product and is abundantly present in marine bacteria. Now, we have approached the in vivo situation by studying the effect of polyP on the human alveolar basal epithelial A549 cells in a mucus-like mucin environment. These cells express mucins as well as the ectoenzymes alkaline phospha…
Synthetic Antitumor Vaccines from Tetanus Toxoid Conjugates of MUC1 Glycopeptides with the Thomsen-Friedenreich Antigen and a Fluorine-Substituted An…
2010
A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting Macrophages and Dendritic Cells
2017
A MUC1 anticancer vaccine equipped with covalently linked divalent mannose ligands was found to improve the antigen uptake and presentation by targeting mannose-receptor-positive macrophages and dendritic cells. It induced much stronger specific IgG immune responses in mice than the non-mannosylated reference vaccine. Mannose coupling also led to increased numbers of macrophages, dendritic cells, and CD4+ T cells in the local lymph organs. Comparison of di- and tetravalent mannose ligands revealed an increased binding of the tetravalent version, suggesting that higher valency improves binding to the mannose receptor. The mannose-coupled vaccine and the non-mannosylated reference vaccine ind…
Nanoscale Mapping of the Physical Surface Properties of Human Buccal Cells and Changes Induced by Saliva
2019
International audience; The mucosal pellicle, also called salivary pellicle, is a thin biological layer made of salivary and epithelial constituents, lining oral mucosae. It contributes to their protection against microbiological, chemical, or mechanical insults. Pellicle formation depends on the cells’ surface properties, and in turn the pellicle deeply modifies such properties. It has been reported that the expression of the transmembrane mucin MUC1 in oral epithelial cells improves the formation of the mucosal pellicle. Here, we describe an approach combining classical and functionalized tip atomic force microscopy and scanning microwave microscopy to characterize how MUC1 induces change…
Understanding retention and metabolization of aroma compounds using an in vitro model of oral mucosa.
2020
International audience; The mechanism leading to aroma persistence during eating is not fully described. This study aims at better understanding the role of the oral mucosa in this phenomenon. Release of 14 volatile compounds from different chemical classes was studied after exposure to in vitro models of oral mucosa, at equilibrium by Gas-Chromatography-Flame Ionization Detection (GC-FID) and in dynamic conditions by Proton Transfer Reaction- Mass Spectrometry (PTR-MS). Measurements at equilibrium showed that mucosal hydration reduced the release of only two compounds, pentan-2-one and linalool (p < 0.05), and suggested that cells could metabolize aroma compounds from different chemical fa…
Implicación de MUC1 como marcador de corticorresistencia en la Enfermedad Pulmonar Obstructiva Crónica
2017
La mayoría de pacientes con Enfermedad Pulmonar Obstructiva Crónica (EPOC) son resistentes incluso a altas dosis de corticosteroides inhalados u orales. Han sido estudiadas varias mucinas (MUCAC y MUC5B) en las vías aéreas principales de pacientes con EPOC pero el potencial papel de MUC1 en la patología como en la aparición de corticorresistencia estaba aún por demostrar. Se conocen propiedades de MUC1 en inflamación de las vías aéreas por estar relacionada con su capacidad para inhibir varios TLR, en particular a través MyD88. Esta inhibición evita diversas cascadas de señalización, que daría lugar a la transcripción de diferentes genes pro-inflamatorios. Además MUC1 también se conoce por …
The development of synthetic antitumour vaccines from mucin glycopeptide antigens.
2013
Based on important cell-biological and biochemical results concerning the structural difference between membrane glycoproteins of normal epithelial cells and epithelial tumour cells, tumour-associated glycopeptide antigens have been chemically synthesised and structurally confirmed. Glycopeptide structures of the tandem repeat sequence of mucin MUC1 of epithelial tumour cells constitute the most promising tumour-associated antigens. In order to generate a sufficient immunogenicity of these endogenous structures, usually tolerated by the immune system, these synthetic glycopeptide antigens were conjugated to immune stimulating components: in fully synthetic two-component vaccines either with…
Synthesis of Fluorinated Glycosyl Amino Acid Building Blocks for MUC1 Cancer Vaccine Candidates by Microreactor-Assisted Glycosylation
2012
Abstract MUC1-type glycopeptides have already shown their potential as possible cancer vaccine candidates. In addition, first examples of fluorinated antigen structures, especially containing the Thomsen–Friedenreich antigen, with similar antibody recognition have been reported. Using microreactor techniques for improvement of the crucial step, the complex glycosylation reactions, is an efficient way to find optimized reaction parameter as well as to circumvent well-known scale-up drawbacks. Besides, this is the first report of continuous flow glycosylations of glycosyl amino acids, in particular with fluorinated glycosyl building blocks.