Deciphering Natural Killer Cell Cytotoxicity Against Medulloblastoma in vitro and in vivo: Implications for Immunotherapy.

Purpose: Medulloblastoma (MB) is the most prevalent paediatric brain tumour. Despite improvements in patient survival with current treatment strategies, the quality of life of these patients remains poor owing to the sequelae and relapse risk. An alternative, or, in addition to the current standard treatment, could be considered immunotherapy, such as Natural Killer cells (NK).

Tissue-specific collagen hydroxylation at GEP/GDP triplets mediated by P4HA2.

Collagen, the most abundant organic compound of vertebrate organisms, is a supramolecular, protein-made polymer. Details of its post-translational maturation largely determine the mechanical properties of connective tissues. Its assembly requires massive, heterogeneous prolyl-4-hydroxylation (P4H), catalyzed by Prolyl-4-hydroxylases (P4HA1-3), providing thermostability to its elemental, triple helical building block.

Characterization of an Innovative Biomaterial Derived From Human Wharton's Jelly as a New Promising Coating for Tissue Engineering Applications.

The extracellular matrix (ECM) offers the opportunity to create a biomaterial consisting of a microenvironment with interesting biological and biophysical properties for improving and regulating cell functions. Animal-derived ECM are the most widely used as an alternative to human tissues that are of very limited availability. However, incomplete decellularization of these tissues presents a high risk of immune rejection and disease transmission.

A versatile strategy to synthesize -methyl-anthranilic acid-labelled glycoprobes for fluorescence-based screening assays.

Here we propose a general strategy to label carbohydrates with N-methyl-anthranilic acid at the anomeric position. Through two examples, we demonstrate that the generated glycoprobes are suitable for fluorescence-based binding/competition assays. Our approach is expected to readily generate series of glycoprobes dedicated to screening assays for the discovery of drugs targeting carbohydrate-protein interactions.

ATDC5 cells as a model of cartilage extracellular matrix neosynthesis, maturation and assembly.

Fibrillar collagens and proteoglycans (PGs) are quantitatively the major constituents of extracellular matrices (ECM). They carry numerous crucial post-translational modifications (PTMs) that tune the resulting biomechanical properties of the corresponding tissues. The mechanisms determining these PTMs remain largely unknown, notably because available established cell lines do not recapitulate much of the complexity of the machineries involved.

Label-free relative quantification of secreted proteins as a non-invasive method for the quality control of chondrogenesis in bioengineered substitutes for cartilage repair.

Cartilage tissue engineering is making progress, but the competing available strategies still leave room for improvement and consensual overviews regarding the best combinations of scaffolds and cell sources are limited by the capacity to compare them directly. In addition, because most strategies involve autologous cell transfer, once these are optimized, the resulting implants require individual quality control prior to grafting in order to emphasize patient-to-patient differential responsiveness to engineering processes. Here, cartilage substitutes prepared from human mesenchymal stem cells undergoing chondrogenic differentiation within distinct scaffolds were used as pilot samples to investigate the pertinence of a novel method with the aim of characterizing the implants.

Effect of nicotine on the proliferation and chondrogenic differentiation of the human Wharton's jelly mesenchymal stem cells.

Background: Osteoarthritis (OA) is a chronic joint disease characterized by a progressive and irreversible degeneration of articular cartilage. Among the environmental risk factors of OA, tobacco consumption features prominently, although, there is a great controversy regarding the role of tobacco smoking in OA development. Among the numerous chemicals present in cigarette smoke, nicotine is one of the most physiologically active molecules.

Albumin as a carrier for NO delivery: preparation, physicochemical characterization, and interaction with gold nanoparticles.

Background: Nitric oxide (NO) is a gaseous transmitter playing numerous physiological roles and characterized by a short half-life. Its binding to endogenous thiols increases its stability, facilitating its storage and transport. The purpose of this study was to investigate the nitrosated serum albumin (SA-SNO) and to provide a reference for its easy preparation for further use in in vitro studies.

In malignant cartilagenous tumors, immunohistochemical expression of procollagen PC1CP peptide is higher and that of PC2CP lower than in benign cartilaginous lesions.

Few studies on oncogenesis of chondrosarcoma (CS) are available in the literature. Our previously published experimental evidence suggests that while the C-propeptide of procollagen Iα1 (PC1CP), a component of cartilage, favors tumor progression, the C-propeptide of procollagen IIα1 (PC2CP) exerts antitumor properties. In this study, we analyzed expression of PC1CP and PC2CP by immunohistochemistry in a series of enchondromas and CS.

Label-free relative quantification applied to LC-MALDI acquisition for rapid analysis of chondrocyte secretion modulation.

Unlabelled: Proteomics users enjoy the rapid development of LC-MS-based label-free relative quantification methods but in practice these remain restricted to mass spectrometers using electrospray ionization. Here, tools dedicated to ion chromatogram extraction, time alignment, signal normalization and statistical analysis were used to interpret label-free relative difference between primary human chondrocyte secretomes and dilutions thereof, analyzed successively by LC-MALDI. The analysis of secretomes diluted into culture medium demonstrated that abundant proteins could be relatively quantified within 1.

Chondrocalcin is internalized by chondrocytes and triggers cartilage destruction via an interleukin-1β-dependent pathway.

Chondrocalcin is among the most highly synthesized polypeptides in cartilage. This protein is released from its parent molecule, type II pro-collagen, after secretion by chondrocytes. A participation of extracellular, isolated chondrocalcin in mineralization was proposed more than 25 years ago, but never demonstrated.

The cucurbitacins E, D and I: investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver.

Cucurbitacins are a class of natural compounds known for their numerous potential pharmacological effects. The purpose of this work was to compare the cytotoxicity of three cucurbitacins I, D, E on the chondrosarcoma SW 1353 cancer cell line and to investigate their biotransformation in man. Cucurbitacins I and D showed a very strong cytotoxicity, which was higher than that of cytochalasin D, used as a drug reference.

Matrilin-3 switches from anti- to pro-anabolic upon integration to the extracellular matrix.

The extracellular matrix (ECM) has long been viewed primarily as an organized network of solid-phase ligands for integrin receptors. During degenerative processes, such as osteoarthritis, the ECM undergoes deterioration, resulting in its remodeling and in the release of some of its components. Matrilin-3 (MATN3) is an almost cartilage specific, pericellular protein acting in the assembly of the ECM of chondrocytes.

Alternative for anti-TNF antibodies for arthritis treatment.

Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, plays a key role in the pathogenesis of many inflammatory diseases, including arthritis. Neutralization of this cytokine by anti-TNF-α antibodies has shown its efficacy in rheumatoid arthritis (RA) and is now widely used. Nevertheless, some patients currently treated with anti-TNF-α remain refractory or become nonresponder to these treatments.

C-propeptides of procollagens I alpha 1 and II that differentially accumulate in enchondromas versus chondrosarcomas regulate tumor cell survival and migration.

Chondrogenic tumors that exhibit benign or malignant behaviors synthesize variable amounts of cartilage-like extracellular matrix. To define the regulators of these phenotypes, we performed a proteomic comparison of multiple human chondrogenic tumors, which revealed differential accumulation of the C-propeptides of procollagens Ialpha1 and II (PC1CP and PC2CP) in malignant versus benign tumors, respectively. Expression patterns of PC1CP correlated with levels of tumor vascularization, whereas expression patterns of PC2CP suggested its susceptibility to immobilization within the extracellular matrix.

Increased expression of matrilin-3 not only in osteoarthritic articular cartilage but also in cartilage-forming tumors, and down-regulation of SOX9 via epidermal growth factor domain 1-dependent signaling.

Objective: To identify regulators of the cartilaginous phenotype, on the basis of their differential expression in human conventional chondrogenic tumors compared with articular cartilage.

Methods: Differential proteomics analysis revealed matrilin-3 (MATN3) as a candidate regulator of the cartilaginous phenotype. Its capacity to modulate gene expression was investigated in human HCS-2/8 chondrosarcoma cells and transfected chondrocytes, using cell culture fractionation, reverse transcription-polymerase chain reaction, and Western blot analyses.

Establishment of a reliable method for direct proteome characterization of human articular cartilage.

Articular cartilage consists mainly of extracellular matrix, mostly made of collagens and proteoglycans. These macromolecules have so far impaired the detailed two-dimensional electrophoresis-based proteomic analysis of articular cartilage. Here we describe a method for selective protein extraction from cartilage, which excludes proteoglycans and collagen species, thus allowing direct profiling of the protein content of cartilage by two-dimensional electrophoresis.

Molecular and functional characterization of SLC26A11, a sodium-independent sulfate transporter from high endothelial venules.

Lymphocyte emigration from the blood into most secondary lymphoid organs and chronically inflamed tissues occurs at the level of high endothelial venules (HEV). A unique characteristic of HEV endothelial cells (HEVEC) is their capacity to incorporate large amounts of sulfate into sialomucin-type counter-receptors for the lymphocyte homing receptor L-selectin. We have previously shown that sulfate uptake into HEVEC is mediated by two distinct functional classes of sulfate transporters: Na+-coupled transporters and sulfate/anion exchangers.

Molecular cloning of SLC26A7, a novel member of the SLC26 sulfate/anion transporter family, from high endothelial venules and kidney.

A unique characteristic of endothelial cells from high endothelial venules (HEVEC) in lymphoid organs and chronically inflamed tissues is their capacity to incorporate large amounts of sulfate into sialomucin-type counter-receptors for the lymphocyte homing receptor L-selectin. We have previously shown that HEVEC express two functional classes of sulfate transporters: sodium/sulfate cotransporters and sulfate/anion exchangers. Here, we report the molecular cloning from human HEVEC of a 2.