Hypoxia-driven heterogeneous expression of α5 integrin in glioblastoma stem cells is linked to HIF-2α.

Despite numerous molecular targeted therapies tested in glioblastoma (GBM), no significant progress in patient survival has been achieved in the last 20 years in the overall population of GBM patients except with TTfield setup associated with the standard of care chemoradiotherapy. Therapy resistance is associated with target expression heterogeneity and plasticity between tumors and in tumor niches. We focused on α5 integrin implicated in aggressive GBM in preclinical and clinical samples.

Dietary supplementation with nacre reduces cortical bone loss in aged female mice.

Aging is associated with detrimental bone loss leading to fragility fractures in both men and women. Notably, a majority of bone loss with aging is cortical, as well as a large number of fractures are non-vertebral and at the non-hip sites. Nacre is a product of mollusks composed of calcium carbonate embedded in organic components.

Stronger than Ever: Multifilament Fiberglass Posts Boost Maxillary Premolar Fracture Resistance.

This paper investigates the influence of cavity configuration and post-endodontic restoration on the fracture resistance, failure mode and stress distribution of premolars by using a method of fracture failure test and finite elements analysis (FEA) coupled to Weibull analysis (WA). One hundred premolars were divided into one control group (G) ( = 10) and three experimental groups, according to the post-endodontic restoration ( = 30), G, restored using composite, G, restored using single fiber post and G, restored using multifilament fiberglass posts (m-FGP) without post-space preparation. Each experimental group was divided into three subgroups according to the type of coronal cavity configuration ( = 10): G, G and G with occlusal (O) cavity configuration; G, G, and G with mesio-occlusal (MO); and G, G, and G with mesio-occluso-distal (MOD).

Treatment of HCC with claudin-1-specific antibodies suppresses carcinogenic signaling and reprograms the tumor microenvironment.

Background & Aims: Despite recent approvals, the response to treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) remain poor. Claudin-1 (CLDN1) is a membrane protein that is expressed at tight junctions, but it can also be exposed non-junctionally, such as on the basolateral membrane of the human hepatocyte. While CLDN1 within tight junctions is well characterized, the role of non-junctional CLDN1 and its role as a therapeutic target in HCC remains unexplored.

Comparison of the [F]-FDG and [F]-FLT PET Tracers in the Evaluation of the Preclinical Proton Therapy Response in Hepatocellular Carcinoma.

Purpose: The main objective of the present study was to compare the 2-deoxy-2-[F]fluoro-D-glucose ([F]-FDG) and 3'-[F]fluoro-3'-deoxythymidine ([F]-FLT) PET imaging biomarkers for the longitudinal follow-up of small animal proton therapy studies in the context of hepatocellular carcinoma (HCC).

Procedures: SK-HEP-1 cells were injected into NMRI nude mice to mimic human HCC. The behavior of [F]-FDG and [F]-FLT tumor uptake was evaluated after proton therapy procedures.

Biological Relevance of RGD-Integrin Subtype-Specific Ligands in Cancer.

Integrins are heterodimeric transmembrane proteins able to connect cells with the micro-environment. They represent a family of receptors involved in almost all the hallmarks of cancer. Integrins recognizing the Arg-Gly-Asp (RGD) peptide in their natural extracellular matrix ligands have been particularly investigated as tumoral therapeutic targets.

Imaging thrombosis with Tc-labeled RAM.1-antibody in vivo.

Introduction: Platelets play a major role in thrombo-embolic diseases, notably by forming a thrombus that can ultimately occlude a vessel. This may provoke ischemic pathologies such as myocardial infarction, stroke or peripheral artery diseases, which represent the major causes of death worldwide. The aim of this study was to evaluate the specificity of radiolabeled Rat-Anti-Mouse antibody (RAM.

O-(2-F-fluoroethyl)-l-tyrosine (F-FET) uptake in insulinoma: first results from a xenograft mouse model and from human.

Introduction: Herein we have evaluated the uptake of O-(2-F-fluoroethyl)-l-tyrosine (F-FET) in insulinoma in comparison with those of 6-F-fluoro-3,4-dihydroxy-l-phenylalanine (F-FDOPA) providing first data from both murine xenograft model and one patient with proved endogenous hyperinsulinemic hypoglycemia.

Methods: Dynamic F-FET and carbidopa-assisted F-FDOPA PET were performed on tumor-bearing nude mice after subcutaneous injection of RIN-m5F murine beta cells and on a 30-year-old man with type-1 multiple endocrine neoplasia and hyperinsulinemic hypoglycemia defined by a positive fasting test.

Results: Seven and three nude mice bearing a RIN-m5F insulinoma xenograft were respectively studied by F-FET and F-FDOPA μPET.

Strontium-Substituted Bioceramics Particles: A New Way to Modulate MCP-1 and Gro-α Production by Human Primary Osteoblastic Cells.

Background: To avoid morbidity and limited availability associated with autografts, synthetic calcium phosphate (CaP) ceramics were extensively developed and used as bone filling materials. Controlling their induced-inflammatory response nevertheless remained a major concern. Strontium-containing CaP ceramics were recently demonstrated for impacting cytokines' secretion pattern of human primary monocytes.

Physicochemical regulation of TGF and VEGF delivery from mesoporous calcium phosphate bone substitutes.

Aim: Determination of the physicochemical parameters governing growth factors (GFs) adsorption and release from mesoporous calcium phosphate ceramics.

Materials & Methods: Six mesoporous calcium phosphate ceramics prepared by soft and hard templating were loaded with two different physiological concentrations of TGF-β1 or VEGF and their in vitro kinetics of adsorption/release were studied.

Results: This low GF loading promotes adsorption on the highest binding sites.

Hemidesmosome integrity protects the colon against colitis and colorectal cancer.

Objective: Epidemiological and clinical data indicate that patients suffering from IBD with long-standing colitis display a higher risk to develop colorectal high-grade dysplasia. Whereas carcinoma invasion and metastasis rely on basement membrane (BM) disruption, experimental evidence is lacking regarding the potential contribution of epithelial cell/BM anchorage on inflammation onset and subsequent neoplastic transformation of inflammatory lesions. Herein, we analyse the role of the α6β4 integrin receptor found in hemidesmosomes that attach intestinal epithelial cells (IECs) to the laminin-containing BM.

Inhibition of primary breast tumor growth and metastasis using a neuropilin-1 transmembrane domain interfering peptide.

The transmembrane domains (TMD) in membrane receptors play a key role in cell signaling. As previously shown by us a peptide targeting the TMD of neuropilin-1 (MTP-NRP1), blocks cell proliferation, cell migration and angiogenesis in vitro, and decreases glioblastoma growth in vivo. We now explored the clinical potential of MTP-NRP1 on breast cancer models and demonstrate that MTP-NRP1 blocks proliferation of several breast cancer lines including the MDA-MB-231, a triple negative human breast cancer cell line.

Automated and efficient radiosynthesis of [(18)F]FLT using a low amount of precursor.

Introduction: Since 1991 until now, many radiosyntheses of [(18)F]FLT have been published. Most of them suffer from side reactions and/or difficult purification related to the large amount of precursor necessary for the labeling step. A fully automated synthesis using only commercial and unmodified materials with a reduced amount of precursor would be desirable.

A fast experimental beam hardening correction method for accurate bone mineral measurements in 3D μCT imaging system.

Bone mineral density plays an important role in the determination of bone strength and fracture risks. Consequently, it is very important to obtain accurate bone mineral density measurements. The microcomputerized tomography system provides 3D information about the architectural properties of bone.

In vitro and in vivo evaluation of the inflammatory potential of various nanoporous hydroxyapatite biomaterials.

Aim: To discriminate the most important physicochemical parameters for bone reconstruction, the inflammatory potential of seven nanoporous hydroxyapatite powders synthesized by hard or soft templating was evaluated both in vitro and in vivo.

Materials & Methods: After physical and chemical characterization of the powders, we studied the production of inflammatory mediators by human primary monocytes after 4 and 24 h in contact with powders, and the host response after 2 weeks implantation in a mouse critical size defect model.

Results: In vitro results highlighted increases in the secretion of TNF-α, IL-1, -8, -10 and proMMP-2 and -9 and decreases in the secretion of IL-6 only for powders prepared by hard templating.

Phosphonated chelates for nuclear imaging.

A series of bis-, tris- and tetra-phosphonated pyridine ligands is presented. In view of their potential use as chelates for radiopharmaceutical applications, the physico-chemical properties of the ligands and of their Co(II), Ni(II), Cu(II), and Zn(II) complexes were studied by means of potentiometry and UV-Vis absorption spectroscopy. The pKa values of the ligands and of the complexes, as well as the stability constants for the formation of the complexes, are presented.

Transmembrane domain targeting peptide antagonizing ErbB2/Neu inhibits breast tumor growth and metastasis.

Breast cancer is still a deadly disease despite major achievements in targeted therapies designed to block ligands or ligand-binding subunits of major tyrosine kinase receptors. Relapse is significant and metastases deleterious, which demands novel strategies for fighting this disease. Here, we report a proof-of-concept experiment demonstrating that small peptides interfering with the transmembrane domain of the tyrosine kinase epidermal growth factor receptor ErbB2 exhibit anticancer properties when used at micromolar dosages in a genetically engineered mouse model of breast cancer.

Potent calcium phosphate nanoparticle surface coating for in vitro and in vivo siRNA delivery: a step toward multifunctional nanovectors.

The present study describes hybrid nanoparticles, built by alternate deposition of siRNA and modified polyethyleneimine (tyrosine-grafted PEI or tyrosine/galactose-grafted PEI) on calcium phosphate nanoparticles. These "easy to produce" nanoparticles (NPs) present an efficient gene silencing effect demonstrated in vitro in a luciferase expressing cell culture model and in vivo in a tumour xenograft mouse model. The luciferase gene silencing percentage reached up to 95% in vitro with biocompatible doses of siRNA.

Inflammatory cell response to calcium phosphate biomaterial particles: an overview.

Bone is a metabolically active and highly organized tissue consisting of a mineral phase of hydroxyapatite (HA) and amorphous calcium phosphate (CaP) crystals deposited in an organic matrix. One objective of bone tissue engineering is to mimic the chemical and structural properties of this complex tissue. CaP ceramics, such as sintered HA and beta-tricalcium phosphate, are widely used as bone substitutes or prosthesis coatings because of their osteoconductive properties.

A clinical assessment of the Mucus Shaver: a device to keep the endotracheal tube free from secretions.

Objective: : We evaluated a new device designed to clean the endotracheal tube in mechanically ventilated patients, the Mucus Shaver.

Design: : Prospective, randomized trial.

Setting: : University hospital intensive care unit.

A new insight into the dissociating effect of strontium on bone resorption and formation.

Calcium phosphates are widely used as biomaterials and strontium (Sr) is known to have the ability to modify the bone balance towards osteosynthesis. In the present study we investigated the capacity of Sr-substituted sol-gel calcium phosphate to modify the expression of genes and proteins involved in extracellular matrix synthesis by primary bone cells. We first determined the most effective concentration of strontium using human primary bone cells.

The effect of zinc on hydroxyapatite-mediated activation of human polymorphonuclear neutrophils and bone implant-associated acute inflammation.

Hydroxyapatite (HA) is widely used as coating biomaterial for prosthesis metal parts and as bone substitute. The release of HA particles induces an inflammatory response and, if uncontrolled, could result in implant loss. At the inflamed site, the polymorphonuclear cells (PMNs) represent the earliest phagocytic cells that predominate the cellular infiltrate.

Polymorphonuclear neutrophil response to hydroxyapatite particles, implication in acute inflammatory reaction.

Hydroxyapatite (HA) is widely used as a bone substitute or coating biomaterial in bone diseases or prosthesis metal parts. The release of HA particles induces an inflammatory response and, if uncontrolled, could result in implant loss. Among the hallmarks of such inflammatory response is early recruitment of the polymorphonuclear cells (PMNs).

Cryo-X-ray analysis-A novel tool to better understand the physicochemical reactions at the bioglass/biological fluid interface.

The present study deals with the short-term physicochemical reactions at the interface between bioactive glass particles [55SiO(2)-20CaO-9P(2)O(5)-12Na(2)O-4MgO. mol%] and biological fluid (Dulbecco Modified Eagle's Medium (DMEM)). The physicochemical reactions within the interface are characterized by scanning transmission electron microscopy (TEM) (STEM) associated with Energy-dispersive X-ray spectroscopy (EDXS).

Antimicrobial-coated endotracheal tubes: an experimental study.

Objective: Antibiotic-resistant bacterial biofilm may quickly form on endotracheal tubes (ETTs) and can enter the lungs, potentially causing pneumonia. In an attempt to prevent bacterial colonization, we developed and tested in an in-vitro study and animal study several antibacterial-coated ETTs (silver sulfadiazine with and without carbon in polyurethane, silver sulfadiazine and chlorhexidine with and without carbon in polyurethane, silver-platinum with and without carbon in polyurethane, chlorhexidine in polyurethane, and rose bengal for UV light). DESIGN, SETTING, ANIMALS, INTERVENTIONS: After preliminary studies, silver sulfadiazine in polyurethane (SSD-ETT) was selected among the coatings to be challenged every 24 h with 10(4)-10(6) Pseudomonas aeruginosa/ml and evaluated at 6 h, 24 h, and 72 h with standard microbiological studies, scanning electron microscopy, and confocal scanning microscopy.