- Cell Image Analysis Techniques
- Animal testing and alternatives
- Immunotherapy and Immune Responses
- Immunotoxicology and immune responses
- Biosimilars and Bioanalytical Methods
- CAR-T cell therapy research
- Advanced Proteomics Techniques and Applications
- Vibrio bacteria research studies
- Mitochondrial Function and Pathology
- Hormonal Regulation and Hypertension
- Gut microbiota and health
- Eosinophilic Esophagitis
- Mass Spectrometry Techniques and Applications
- Retinal Imaging and Analysis
- Hepatitis B Virus Studies
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Apelin-related biomedical research
- Circadian rhythm and melatonin
- Hepatitis C virus research
- Liver Disease Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Pharmacogenetics and Drug Metabolism
- IL-33, ST2, and ILC Pathways
- Clostridium difficile and Clostridium perfringens research
Roche (Switzerland)
2006-2023
William Harvey Research Institute
2016
Queen Mary University of London
2016
We developed cergutuzumab amunaleukin (CEA-IL2v, RG7813), a novel monomeric CEA-targeted immunocytokine, that comprises single IL-2 variant (IL2v) moiety with abolished CD25 binding, fused to the C-terminus of high affinity, bivalent carcinoembryonic antigen (CEA)-specific antibody devoid Fc-mediated effector functions. Its molecular design aims (i) avoid preferential activation regulatory T-cells vs. immune cells by removing binding; (ii) increase therapeutic index therapy (a) retention at...
Adverse drug effects are often associated with pathological changes in tissue. An accurate depiction of the undesired affected area, possibly supported by mechanistic data, is important to classify regard relevance for human patients. MALDI imaging MS represents a new analytical tool directly provide spatial distribution and relative abundance proteins Here we evaluate this technique investigate potential toxicity biomarkers kidneys rats that were administered gentamicin, well known...
Primary hyperaldosteronism is a common cause of resistant hypertension. Aldosterone produced in the adrenal by aldosterone synthase (AS, encoded gene CYP11B2). AS shares 93% homology to 11β-hydroxylase (encoded CYP11B1), responsible for cortisol production. This has hitherto impeded development drug, which selectively suppresses but not production, as new treatment primary hyperaldosteronism. We now report RO6836191 potent (Ki 13 nmol/L) competitive inhibitor AS, with vitro selectivity...
Quantification of retinal atrophy, caused by therapeutics and/or light, manual measurement layers is labor intensive and time-consuming. In this study, we explored the role deep learning (DL) in automating assessment particularly outer inner nuclear layers, rats. Herein, report our experience creating employing a hybrid approach, which combines conventional image processing DL to quantify rodent atrophy. Utilizing approach based upon VGG16 model architecture, models were trained, tested,...
Conventional treatment of chronic hepatitis B (CHB) is rarely curative due to the immunotolerant status patients. RG7854 an oral double prodrug a toll-like receptor 7 (TLR7) agonist that developed for CHB. The therapeutic efficacy, host immune response, and safety were evaluated in woodchuck model Monotreatment with two highest doses combination dose entecavir (ETV) suppressed viral replication, led loss antigens, induced seroconversion responder woodchucks. Since suppression high-titer...
The γ -secretase complex is a promising target in Alzheimer’s disease because of its role the amyloidogenic processing β -amyloid precursor protein. This enzyme also catalyzes cleavage Notch receptor, resulting nuclear translocation intracellular where it modulates gene transcription. signaling essential cell fate decisions during embryogenesis, neuronal differentiation, hematopoiesis, and development T B cells, including splenic marginal zone (MZ) cells. compartment participates early...
Electronic images of histopathological changes are commonly and increasingly used in toxicologic pathology for morphological evaluation, illustration, peer review, or reporting. Toxicity studies which cell proliferation is an end point also pivotal determining the carcinogenic potential new molecules. In this article, we describe approach European Cell Proliferation Apoptosis working group (CEPA) performing morphometry using electronic images. The Society Toxicologic Pathology (STP) has...
Abstract Our bodies are home to individual-specific microbial ecosystems that have recently been found be modified by cancer immunotherapies. The interaction between the gut microbiome and islet autoimmunity leading type I diabetes (T1D) is well described highlights contribution during onset T1D development in animals humans. As immunotherapies induce perturbations immune-mediated adverse events susceptible patients, we hypothesized NOD mice can used as a predictive tool investigate effects...
Introduction Carnitine palmitoyltransferases (CPT1 and 2) regulate the rate of fatty acid oxidation through intake long‐chain acids (LCFA) into mitochondria. Inhibition CPT can reduce gluconeogenesis by decreasing LCFA acetyl‐CoA in liver. inhibitors are therefore proposed as a potential therapeutic approach to hyperglycemia diabetes. Inborn human deficiency is associated with multiorgan toxicity such muscle weakness, rhabdomyolyis, myoglobinuria, tissue accumulation lipids acylcarnitines,...
In nonrodent toxicity studies that are usually conducted in cynomolgus monkeys or beagle dogs, the added value of examining all tissues from dose groups (current practice) versus only control and high-dose target intermediate-dose by default, is a subject debate. A previous retrospective review 325 included limited number biotherapeutics suggested evaluation was not justified as routine practice recommended examination groups. contrast, present which examined 213 (212 1 dog) 4 multinational...