A5071912049- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Nanoplatforms for cancer theranostics
- Virus-based gene therapy research
- Tendon Structure and Treatment
- Cancer Cells and Metastasis
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Animal Genetics and Reproduction
- Neuroinflammation and Neurodegeneration Mechanisms
- Cystic Fibrosis Research Advances
- Exercise and Physiological Responses
- Neurogenesis and neuroplasticity mechanisms
- Muscle Physiology and Disorders
- Sports injuries and prevention
- Advanced Biosensing Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- 3D Printing in Biomedical Research
- Multiple Sclerosis Research Studies
- Silk-based biomaterials and applications
- RNA regulation and disease
- Neuroscience and Neural Engineering
- Ultrasound Imaging and Elastography
- Chemokine receptors and signaling
Novartis (Switzerland)
2014-2025
Novartis Institutes for BioMedical Research
2014-2023
Transgene (France)
1994-2014
Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). While multiple effective immunomodulatory therapies for MS exist today, they lack scope of promoting CNS repair, in particular remyelination. Microglia play pivotal role regulating myelination processes, and colony-stimulating factor 1 (CSF-1) pathway key regulator microglia differentiation survival. Here, we investigated effects CSF-1 receptor kinase inhibitor, BLZ945, on processes 5-week...
Abstract Resistance to therapy and lack of curative treatments for metastatic breast cancer suggest that current therapies may be missing the subpopulation chemoresistant radioresistant stem cells (CSC). The ultimate success any treatment well rest on CSC eradication, but specific anti-CSC are still limited. A comparison transcriptional profiles murine Her2+ tumor TUBO their derived CSC-enriched tumorspheres has identified xCT, functional subunit cystine/glutamate antiporter system xc−, as a...
Ad CFTR, a replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator (CFTR), was administered by aerosolization in single escalating dose to three pairs (cohorts) of (CF) patients. Buffer only nose and lungs 9–14 days before nasal instillation virus followed day after CFTR lung. Nasal doses (defined terms viral plaque forming units, pfu) were 105, 107, 4 × 108, whereas aerosolized 5.4 108 for each cohort, respectively. No acute toxic effects...
Abstract Hydrogels are under active development for controlled drug delivery, but their clinical translation is limited by low loading capacity, deficiencies in mechanical toughness and storage stability, poor control over the release that often results burst short duration. This work reports a design of composite clay hydrogels, which simultaneously achieve spectrum mechanical, storage, loading/releasing properties to address critical needs from translational perspectives. The nanoparticles...
Abstract A key to enhance the low translatability of preclinical drug discovery are in vitro human three-dimensional (3D) microphysiological systems (MPS). Here, we show a new method for automated engineering 3D skeletal muscle models microplates and functional compound screening address lack wasting disease medication. To this end, adapted our recently described 24-well plate bioprinting platform with printhead cooling system allow microvalve-based drop-on-demand printing cell-laden...
Objective Colony‐stimulating factor 1 receptor (CSF‐1R) essentially modulates monocyte proliferation, migration, and activation, which are considered important for the pathogenesis of rheumatoid arthritis (RA). We undertook this study to determine CSF‐1R expression in human RA as well efficacy a specific anti–CSF‐1R monoclonal antibody (AFS98) 2 different animal models RA. Methods was examined blood, synovium, bone samples from patients, osteoarthritis (OA) healthy subjects. The AFS98 by...
Tumor progression is promoted by Tumor-Associated Macrophages (TAMs) and metastasis-induced bone destruction osteoclasts. Both myeloid cell types depend on the CD115-CSF-1 pathway for their differentiation function. We used 3 different mouse cancer models to study effects of targeting host cells with a monoclonal antibody (mAb) capable blocking CSF-1 binding murine CD115. In mice bearing sub-cutaneous EL4 tumors, which are CD115-negative, anti-CD115 mAb depleted F4/80+ CD163+ M2-type TAMs...
Age-related loss of skeletal muscle innervation by motor neurons leads to impaired neuromuscular function and is a well-established clinical phenomenon. However, the underlying pathogenesis remains unclear. Studying mice, we find that number units (MUs) can be maintained counteracting neurotoxic microglia in aged spinal cord. We observe marked changes, detected unit estimation (MUNE), occur prior mice. This coincides with gene expression changes indicative neuronal remodeling microglial...
Objectives Tendinopathy is a frequent clinical problem and represents an extraordinary health economic socioeconomic burden with high unmet medical needs. Recent evidence suggests blockade of interleukin 17A (IL-17A) for tendinopathy therapy. The present preclinical study elucidates the biological mechanisms IL-17A pathway stimulation in tendinopathy. Methods We explored whether other IL-17 family members are differentially expressed biopsies healthy, early-stage late-stage tendinopathic...
Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity alveolar surface area, secondary to epithelial cell injury, reactive inflammation, proliferation fibroblasts, deposition extracellular matrix. The effects oropharyngeal aspiration bleomycin in Sprague-Dawley rats C57BL/6 mice, as well intratracheal administration ovalbumin actively sensitized Brown Norway on total volume assessed noninvasively magnetic resonance imaging (MRI) were...
Oncolytic virotherapy is an emergent promising therapeutic approach for the treatment of cancer. We have constructed a vaccinia virus (WR strain) deleted thymidine kinase (TK) and ribonucleotide reductase (RR) genes that expressed fusion suicide gene FCU1 derived from yeast cytosine deaminase uracil phosphoribosyltransferase genes. evaluated this construct (VV-FCU1) in orthotopic model renal carcinoma (RenCa). Systemic administration VV-FCU1 resulted tumor growth inhibition, despite...
Assessment of myelin integrity in peripheral nerve injuries and pathologies has largely been limited to post-mortem analysis owing the difficulty obtaining biopsies without affecting function. This is further encumbered by small size tissue its location. Therefore, development robust, non-invasive methods highly attractive. In this study, we used magnetic resonance imaging (MRI) techniques, including magnetization transfer ratio (MTR), longitudinally non-invasively characterize both sciatic...
Primary cutaneous lymphomas (CLs), characterized by an accumulation of clonal T or B lymphocytes preferentially localized in the skin, have been successfully treated with interferons (IFNs) which counterbalance Th2-immunosuppressive state associated this pathology. In a phase I/II clinical trial, we correlated local immune infiltrate and anti-tumor effects repeated intralesional administrations adenovirus vector expressing human interferon-gamma (IFN-g) termed TG1042, patients advanced...
Abstract The objective of this work was to assess the consequences repeated intra-articular injection monosodium urate (MSU) crystals with inflammasome priming by lipopolysaccharide (LPS) in order simulate recurrent bouts gout rats. Translational imaging applied simultaneously detect and quantify injury different areas knee joint. MSU/LPS induced joint swelling, synovial membrane thickening, fibrosis infrapatellar fat pad, tidemark breaching, cartilage invasion inflammatory cells. A higher...
Organ-specific cell types are maintained by tissue homeostasis and may vary in nature and/or frequency pathological situations. Moreover, within a lineage, some sub-populations, defined combinations of cell-surface markers, have specific functions. Dendritic cells the epitome such population as they be subdivided into discrete sub-groups with functions compartments various organs. Technically, to study distribution DC it involves performing multiparametric immunofluorescence on...
To redress the immune imbalances created by pathologies such as cancer, it would be beneficial to create novel cytokine molecules, which combine desired activities with reduced toxicities. Due their divergent but complementary activities, is of interest interleukin-2 (IL-2) and IL-18 into one recombinant molecule for immunotherapy. Evaluation a fusokine protein that combines murine IL-2/IL-18 shows stable, maintains IL-2 bioactivities, has notably associated toxicities,...
A novel type of synthetic vector, termed solvoplex, is described that can greatly enhance gene expression in lung after intrapulmonary delivery. Solvoplexes consist plasmid DNA and organic solvents. Several solvents were analyzed, luciferase reporter was observed delivery solvoplexes containing DPSO (di-n-propylsulfoxide), TMU (tetramethylurea), or BMSO (butylmethylsulfoxide). Expression levels correlated with the amount solvent used at constant amounts. Highest obtained intratracheal...
The chicken chorioallantoic membrane (CAM) assay represents one of the most widely used in vivo screening for genes with angiogenic (blood vessel-inducing) or angiostatic (inhibition vessel formation their destruction) activities. Here we show that adenovirus gene transfer vectors infect cells CAM and lead to expression viral transgene. Furthermore, infection an vector containing human vascular endothelial growth factor induced new blood vessels. This improved method saves a considerable...