A5102756996- Liver Disease Diagnosis and Treatment
- DNA Repair Mechanisms
- Liver Disease and Transplantation
- DNA and Nucleic Acid Chemistry
- Carcinogens and Genotoxicity Assessment
- Cancer Genomics and Diagnostics
- Pediatric Hepatobiliary Diseases and Treatments
- Endoplasmic Reticulum Stress and Disease
- Liver physiology and pathology
- Drug Transport and Resistance Mechanisms
- Evolution and Genetic Dynamics
- Pancreatic and Hepatic Oncology Research
- Molecular Biology Techniques and Applications
- Organ Transplantation Techniques and Outcomes
- Lipid metabolism and disorders
- Radiation Therapy and Dosimetry
- Hepatocellular Carcinoma Treatment and Prognosis
- Immunodeficiency and Autoimmune Disorders
- Personal Information Management and User Behavior
- Galectins and Cancer Biology
- Protease and Inhibitor Mechanisms
- Helicobacter pylori-related gastroenterology studies
- Nutrition, Genetics, and Disease
- FOXO transcription factor regulation
- Cancer Cells and Metastasis
Cambridge University Hospitals NHS Foundation Trust
2014-2024
Addenbrooke's Hospital
2008-2021
American College of Clinical Pharmacy
2021
University of North Carolina at Pembroke
2021
University of Cambridge
2019-2020
The Royal Free Hospital
2003-2020
University College London
2003-2020
Istituto Pasteur
2020
Sapienza University of Rome
2020
National Health Service
2009-2017
Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers in part because it insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that refractory clinically used drug gemcitabine, we found tumors this were poorly perfused and vascularized, properties are shared with PDA. We tested whether delivery efficacy gemcitabine mice could be improved by coadministration IPI-926, depletes tumor-associated stromal tissue inhibition Hedgehog cellular signaling...
Liver biopsy is required when clinically important information about the diagnosis, prognosis or management of a patient cannot be obtained by safer means, for research purposes. There are several approaches to liver but predominantly percutaneous transvenous used. A wide choice needles available and approach type needle used will depend on clinical state local expertise but, non-lesional biopsies, 16-gauge recommended. Many patients with disease have abnormal laboratory coagulation tests...
Organoids regenerate human bile ducts Bile carry from the liver and gall bladder to small intestine, where it aids digestion. Cholangiocytes are epithelial cells that line modify as its transported through biliary tree. Chronic diseases involving cholangiocytes account for a large fraction of failure need transplantation. Because donors in short supply, Sampaziotis et al. used organoid technology develop cell-based therapy using tissue (see Perspective by Kurial Willenbring). Cholangiocyte...
Abstract Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2) 1 , could represent a new chemoprophylactic approach for COVID-19 that complements vaccination 2,3 . However, the mechanisms control expression of ACE2 remain unclear. Here we show farnesoid X receptor (FXR) is direct regulator transcription in several tissues affected COVID-19, including gastrointestinal and respiratory systems. We then use over-the-counter compound...
Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty disease, encompasses steatosis and metabolic steatohepatitis (MASH), leading to cirrhosis hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human yet be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, histopathology, transcriptome benchmarked against humans) of murine...
Five experiments examined the influence of opiate antagonists on both short-term analgesic reaction resulting 30 min after exposure to inescapable shock and long-term reexposure 24 hr exposure. Experiment 1 showed that could be reduced by administration naltrexone prior tail shock. 2 reduction in produced was dose-dependent. 3 also 4 large dose naloxone 5 administered Some implications these results for biochemical substrates learned helplessness stress-induced analgesia are discussed.
Ischemia/reperfusion injury (IRI) that develops after liver implantation may prejudice long-term graft survival, but it remains poorly understood. Here we correlate the severity of IRIs were determined by histological grading time-zero biopsies sampled revascularization with patient and outcomes. Time-zero 476 transplants performed at our center between 2000 2010 graded as follows: nil (10.5%), mild (58.8%), moderate (26.1%), severe (4.6%). Severe IRI was associated donor age, donation...
IntroductionHepatotoxicity from T-cell checkpoint blockade is an increasingly common immune-related adverse event, but remains poorly characterised and can be challenging to manage. Such toxicity generally considered resemble autoimmune hepatitis, although this assumption extrapolated limited clinicopathological reports of anti-cytotoxic T-lymphocyte-associated protein 4-induced hepatotoxicity.MethodsHere we report, with full correlation, three cases inhibitor-induced hepatotoxicity...
OBJECTIVES: A severe enteropathy of unknown etiology can be associated with common variable immunodeficiency (CVID). METHODS: Stool and archived small intestinal mucosal biopsies from patients CVID were analyzed by PCR for the presence Norovirus RNA. The products sequenced to determine relationship viral isolates. samples 10 but no served as controls. RESULTS: All eight in our cohort showed persistent fecal excretion Norovirus. Analysis duodenal revealed a strong association between villous...
Abstract RNF43/ZNRF3 negatively regulate WNT signalling. Both genes are mutated in several types of cancers, however, their contribution to liver disease is unknown. Here we describe that hepatocyte-specific loss Rnf43 / Znrf3 results steatohepatitis and increase unsaturated lipids, the absence dietary fat supplementation. Upon injury, deletion defective hepatocyte regeneration cancer, caused by an imbalance between differentiation/proliferation. Using hepatocyte-, hepatoblast- ductal...
SummaryUsing the neutral filter elution technique, induction of DNA double-strand breaks (dsb) has been measured in 250 kVp X-irradiated V79-379A Chinese hamster cells irradiated under air or nitrogen. The dose–effect curves for induced dsb were curvilinear, mirroring cell survival curves, such that there was an approximately linear relationship between and lethal lesions (− ln (cell survival)) which independent oxygen. With with 2·3 MeV neutrons 238Pu α-particles correlations events dsb,...
Abstract Methionine-1 (M1)-linked polyubiquitin chains conjugated by the linear ubiquitin chain assembly complex (LUBAC) control NF-κB activation, immune homoeostasis, and prevents tumour necrosis factor (TNF)-induced cell death. The deubiquitinase OTULIN negatively regulates M1-linked signalling removing LUBAC, deficiency causes OTULIN-related autoinflammatory syndrome (ORAS) in humans. However, cellular pathways physiological functions controlled remain poorly understood. Here, we show...
The SALVE Histopathology Group (SHG) developed and validated a grading staging system for the clinical full histological spectrum of alcohol-related liver disease (ALD) evaluated its prognostic utility in multinational cohort 445 patients.SALVE grade was described by semiquantitative scores steatosis, activity (hepatocellular injury lobular neutrophils) cholestasis. diagnosis steatohepatitis due to ALD (histological ASH, hASH) based on presence hepatocellular ballooning neutrophils. Fibrosis...
SummaryHydrogen peroxide induces lesions in cells similar to those from ionizing radiation, by a Fenton-type production of hydroxyl radicals. At 4°C significant levels DNA single-strand breaks (ssb) could be measured using the alkaline elution technique, after 20-min incubation with 10−5 mol dm−3 H2O2. Only at higher concentrations H2O2 (> 10−4 dm−3) where ssb corresponded that induced more than 18 Gy X-rays, was any cell killing detected clonogenic assay. Cell observed coincide measurement...
SummaryThe effectiveness of low-energy (below 2 MeV) protons at inducing DNA damage in the form single- and double-strand breaks has been determined. Protons with mean energies 1·90 MeV, 1·15 MeV 0·76 corresponding to track average LETs 17 keV/μm, 24 keV/μm 32 respectively, have used compared 250 kVp X-rays 3·8 238Pu α-particles. Although there was variation RBE for ssb induction LET, RBEs dsb all three proton α-particles were around 1·0. This suggests that, if are important...
Liver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) but role of liver disease aetiology in cancer development remains under-explored. We investigated global gene expression profiles from HCC arising different diseases to test whether driven by common or genes, which could provide new diagnostic markers therapeutic targets.Global profiling was performed 4 normal (control) livers as well 8 background and 7 3 patients with hereditary haemochromatosis (HH)...