A5028008959- Glioma Diagnosis and Treatment
- Brain Metastases and Treatment
- Ferroptosis and cancer prognosis
- Radiopharmaceutical Chemistry and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Cytokine Signaling Pathways and Interactions
- Multiple Sclerosis Research Studies
- Systemic Lupus Erythematosus Research
- Advanced MRI Techniques and Applications
- Nanoplatforms for cancer theranostics
- Diet and metabolism studies
- Chemical Reactions and Isotopes
- Cancer, Hypoxia, and Metabolism
- Cell Adhesion Molecules Research
- Epilepsy research and treatment
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Parkinson's Disease Mechanisms and Treatments
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Cancer, Stress, Anesthesia, and Immune Response
- Eicosanoids and Hypertension Pharmacology
- Brain Tumor Detection and Classification
- MicroRNA in disease regulation
- Nanoparticle-Based Drug Delivery
University of Nottingham
2016-2025
Medical Research Council
2011-2024
Cancer Research UK
2011-2024
Churchill Hospital
2008-2024
University of Oxford
2013-2024
Nottingham Biomedical Research Centre
2023
Queen's Medical Centre
2023
National Institute for Health Research
2023
Versus Arthritis
2023
CRUK/MRC Oxford Institute for Radiation Oncology
2008-2019
Abstract Aims According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads brain through vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) humans can progress with emergence of pathogenic α‐synuclein (α‐syn) gastrointestinal tract midbrain dopaminergic neurons. Methods We have analysed gut ventral from subjects previously diagnosed IBD form a DSS‐based rat model inflammation terms...
Abstract Background and Objective Inflammatory bowel disease (IBD) fatigue aetiology is poorly understood. This study quantified body composition physical function alongside proton magnetic resonance imaging (1H MRI) spectroscopy (31P MRS) measures of organ structure in quiescent Crohn’s patients (CD) healthy volunteers (HVs), to identify a physiological basis for IBD fatigue. Methods Body was determined using dual-energy X-ray absorptiometry 1H MRI. Knee extensor isometric strength...
Initial recruitment of leukocytes in inflammation associated with diseases such as multiple sclerosis (MS), ischemic stroke, and HIV-related dementia, takes place across intact, but activated brain endothelium. It is therefore undetectable to symptom-based diagnoses cannot be observed by conventional imaging techniques, which rely on increased permeability the blood-brain barrier (BBB) later stages disease. Specific visualization early-activated cerebral endothelium would provide a powerful...
Metastasis to the brain is a leading cause of cancer mortality. The current diagnostic method gadolinium-enhanced MRI sensitive only larger tumors, when therapeutic options are limited. Earlier detection metastases critical for improved treatment. We have developed targeted contrast agent based on microparticles iron oxide that enables imaging endothelial vascular cell adhesion molecule-1 (VCAM-1). Our objectives here were determine whether VCAM-1 up-regulated vessels associated with...
Cellular adhesion molecules (CAMs), which are normally associated with leukocyte trafficking, have also been shown to play an essential role in tumor metastasis non-CNS sites. However, the played by CAMs brain is largely unexplored. It known that recruitment very atypical and mechanisms of disease peripheral tissues cannot be extrapolated brain. Here, we established spatiotemporal expression 12 key initial phases seeding 2 different models metastasis. BALB/c or SCID mice were injected...
The potential association between microbial infection and reactivation of a multiple sclerosis (MS) lesion is an important issue that remains unresolved, primarily because the absence suitable animal models imaging techniques. Here, we have evaluated this question in empirical manner using immunohistochemistry magnetic resonance (MRI), before after induction systemic inflammatory response two distinct MS. In pattern-II-type focal myelin oligodendrocyte glycoprotein-experimental autoimmune...
Hyperpolarised MRI with Dynamic Nuclear Polarisation overcomes the fundamental thermodynamic limitations of conventional magnetic resonance, and is translating to human studies several early-phase clinical trials in progress including early reports that demonstrate utility technique observe lactate production brain cancer patients. Owing coupling metabolism tissue function, metabolic neuroimaging hyperpolarised [1-
Diagnosis of multiple sclerosis (MS) currently requires lesion identification by gadolinium (Gd)-enhanced or T2-weighted magnetic resonance imaging (MRI). However, these methods only identify late-stage pathology associated with blood-brain barrier breakdown. There is a growing belief that more widespread, but undetectable, present in the MS brain. We have previously demonstrated an anti-VCAM-1 antibody conjugated to microparticles iron oxide (VCAM-MPIO) enables vivo detection VCAM-1 MRI....
Article27 May 2016Open Access Source DataTransparent process SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and medulloblastoma development Madalina Raducu Cancer Research UK Medical Council Institute for Radiation Oncology, Department University Oxford, Search more papers by this author Ella Fung Sébastien Serres Paola Infante Center Life [email protected], Istituto Italiano di Tecnologia, Rome, Italy Alessandro Barberis Roman Fischer Target Discovery Institute, Nuffield...
Abstract Ligand-conjugated microparticles of iron oxide (MPIO) have the potential to provide high sensitivity contrast for molecular magnetic resonance imaging (MRI). However, accumulation and persistence non-biodegradable micron-sized particles in liver spleen precludes their clinical use limits translational MPIO-based agents. Here we show that ligand-targeted MPIO derived from multiple nanoparticles may be coupled covalently through peptide linkers are designed cleaved by intracellular...
Carbon metabolism in the rat brain was studied animals anesthetized with a light dose of pentobarbital and awake under morphine, which were infused either [1- 13 C]glucose+acetate or glucose+[2- C]acetate for various periods time. Brain amino-acid enrichments tissue extracts determined by nuclear magnetic resonance (NMR) spectroscopy their time evolution analyzed automatic fitting. Acetyl-coenzyme A C2 enrichment ratio between pyruvate carboxylase dehydrogenase activity (PC/PDH) from...
Abstract The role of Notch signaling and its ligand JAGGED1 (JAG1) in tumor biology has been firmly established, making them appealing therapeutic targets for cancer treatment. Here, we report the development characterization human/rat-specific JAG1-neutralizing mAbs. Epitope mapping identified their binding to receptor interaction site within JAG1 Delta/Serrate/Lag2 domain, where E228D substitution prevented effective murine Jag1 ortholog. These antibodies were able specifically inhibit...
IL-17 is argued to play an important role in the multiple sclerosis-like disease experimental autoimmune encephalitis (EAE). We investigated therapeutic effects of anti-IL-17A a chronic relapsing EAE ABH mouse model using conventional scoring, quantitative behavioral outcomes, and novel vascular cell adhesion molecule 1 (VCAM-1)-targeted magnetic resonance imaging (MRI) contrast agent [anti-VCAM-microparticles iron oxide (MPIO)] identify conventionally undetectable neuropathology. Mice were...
Metastatic spread of cancer cells to the brain is associated with high mortality, primarily because current diagnostic tools identify only well-advanced metastases. Brain metastases have been shown induce a robust glial response, including both astrocyte and microglial activation. On basis these findings, we hypothesized that this stromal response may provide sensitive biomarker tumor burden, in particular through use SPECT/PET imaging agents targeting translocator protein (TSPO) upregulated...
Neuroinflammation has been identified as a potential therapeutic target in amyotrophic lateral sclerosis (ALS), but relevant biomarkers are needed. The superoxide dismutase (SOD1) G93A transgenic mouse model of ALS offers unique opportunity to study and potentially manipulate presymptomatic pathology. While T 2 -weighted magnetic resonance imaging (MRI) shown be sensitive pathologic changes at symptom onset, no earlier were previously the underlying histopathologic correlates remain...
Astrocytes are thought to play a pivotal role in coupling neural activity and cerebral blood flow. However, it has been shown that astrocytes undergo morphologic changes response brain metastasis, switching reactive phenotype, which the potential significantly compromise cerebrovascular function contribute neurological sequelae associated with metastasis. Given STAT3 is key regulator of astrocyte reactivity, we aimed here determine impact STAT3-mediated reactivity on neurovascular Rat models...
Abstract Purpose: Despite optimal local therapy, tumor cell invasion into normal brain parenchyma frequently results in recurrence patients with solid tumors. The aim of this study was to determine whether microvascular inflammation can be targeted better delineate the tumor-brain interface through vascular adhesion molecule-1 (VCAM-1)-targeted MRI. Experimental Design: Intracerebral xenograft rat models MDA231Br-GFP (breast cancer) metastasis and U87MG (glioblastoma) were used...
Abstract The majority of individuals with multiple sclerosis (MS) exhibit T‐cell‐ and macrophage‐dominated lesions (patterns I II; as opposed to III IV). These lesions, in turn, may be distinguished on the basis whether or not there are immunoglobulin complement depositions at sites active myelin destruction; such found exclusively pattern II lesions. main aim this study was determine MS distinct MRI signatures. We have used a recently described focal MOG‐induced EAE model rat brain, which...
Brain metabolism of glucose and lactate was analyzed by ex vivo NMR spectroscopy in rats presenting different cerebral activities induced after the administration pentobarbital, alpha-chloralose, or morphine. The animals were infused with a solution either [1-(13)C]glucose plus [3-(13)C]lactate for 20 min. metabolite contents enrichments determined from analyses brain tissue perchloric acid extracts according to their post-mortem evolution kinetics. When amino compared, both metabolic...
Metastasis to the brain results in significant impairment of function and poor patient survival. Currently, magnetic resonance imaging (MRI) is under‐utilised monitoring metastases their effects on function. Here, we sought establish a model focal metastasis rat that enables serial multimodal structural functional MRI studies, assess sensitivity these approaches metastatic growth. Female Berlin–Druckrey‐IX rats were injected intracerebrally with ENU1564 cells ventroposterior medial nucleus...
Abstract Lung cancer patients frequently develop brain metastases (BM). Despite aggressive treatment including neurosurgery and external-radiotherapy, overall survival remains poor. There is a pressing need to further characterize factors in the microenvironment of BM that may confer resistance radiotherapy (RT), such as hypoxia. Here, hypoxia was first evaluated 28 biopsies from with non‑small cell lung (NSCLC) BM, using CA-IX immunostaining. Hypoxia characterization (pimonidazole, HIF-1α)...