A5056241510- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Adipokines, Inflammation, and Metabolic Diseases
- Regulation of Appetite and Obesity
- Cell Adhesion Molecules Research
- Biochemical Analysis and Sensing Techniques
- Immune Response and Inflammation
- Asthma and respiratory diseases
- Toxin Mechanisms and Immunotoxins
- Immune Cell Function and Interaction
- Inflammasome and immune disorders
- Inflammatory Bowel Disease
- Biosimilars and Bioanalytical Methods
- CAR-T cell therapy research
- Respiratory and Cough-Related Research
- Immunodeficiency and Autoimmune Disorders
- T-cell and B-cell Immunology
- Adipose Tissue and Metabolism
- Cytokine Signaling Pathways and Interactions
- Pharmaceutical studies and practices
- Receptor Mechanisms and Signaling
- Chronic Lymphocytic Leukemia Research
- Fatty Acid Research and Health
- Curcumin's Biomedical Applications
- Sepsis Diagnosis and Treatment
AstraZeneca (Singapore)
2025
AstraZeneca (United States)
2020-2024
Exelixis (United States)
2022-2024
Serimmune (United States)
2017
Amgen (United States)
2001-2003
San Francisco VA Medical Center
1998-2002
University of California, San Francisco
1998-2002
University of Colorado Health
2000-2002
Electronic Sensor Technology (United States)
2001
University of Colorado Anschutz Medical Campus
2000
Abstract Leptin, the product of ob gene, is a pleiotropic molecule that regulates food intake as well metabolic and endocrine functions. Leptin also plays regulatory role in immunity, inflammation, hematopoiesis. Alterations immune inflammatory responses are present leptin- or leptin-receptor-deficient animals, during starvation malnutrition, two conditions characterized by low levels circulating leptin. Both leptin its receptor share structural functional similarities with interleukin-6...
Systemic and localized inflammation elicit a number of host responses which include fever, cachexia, hypoglycemia, major changes in the concentration liver plasma proteins. Interleukin 6 (IL-6) is considered an important mediator inflammatory response, together with IL-1 tumor necrosis factor alpha (TNF-alpha). The purpose this study was to unequivocally determine role IL-6 these phenomena making use IL-6-deficient mice that we have recently generated by gene targeting. We report here...
Pre-clinical data demonstrate a pivotal role for interleukin (IL)-13 in the development and maintenance of asthma. This study assessed effects tralokinumab, an investigational human IL-13-neutralising immunoglobulin G4 monoclonal antibody, adults with moderate-to-severe uncontrolled asthma despite controller therapies. 194 subjects were randomised to receive tralokinumab (150, 300 or 600 mg) placebo subcutaneously every 2 weeks. Primary end-point was change from baseline mean Asthma Control...
MEDI2070 is a human monoclonal antibody that selectively inhibits interleukin 23 (IL23), cytokine implicated in the pathogenesis of Crohn's disease (CD). We analyzed its safety and efficacy treatment CD phase 2a study.We conducted double-blind, placebo-controlled study 119 adults with moderate to severe failed by tumor necrosis factor antagonists. Patients were randomly assigned (1:1) groups given (700 mg) or placebo intravenously at weeks 0 4. received open-label (210 subcutaneously every 4...
The role of leptin was investigated in two models T cell-mediated hepatitis: the administration Con A or Pseudomonas aeruginosa exotoxin (PEA). In both models, leptin-deficient (ob/ob) mice were protected from liver damage and showed lower induction tumor necrosis factor (TNF) alpha IL-18 compared with their lean littermates. Neutralization TNF-alpha reduced by either (70% reduction) PEA (40% reduction). Pretreatment soluble TNF receptors an anti-IL-18 antiserum significantly A- PEA-induced...
Interleukins (IL) are key mediators of the host response to infection and inflammation. Leptin is secreted by adipose tissue plays an important role in control food intake. Administration lipopolysaccharide (LPS), tumor necrosis factor (TNF), or IL-1 acutely increases leptin mRNA protein levels. To investigate IL-1β IL-6 expression during inflammation, we used IL-1β-deficient (−/−) −/− mice. Mice were injected intraperitoneally with LPS subcutaneously turpentine, as models systemic local...
Leptin is induced by lipopolysaccharide (LPS) and cytokines. We investigated the role of leptin in LPS-induced toxicity using leptin-deficient ( ob/ ob) receptor-deficient db/ db) mice. Sensitivity to mortality significantly greater obmice compared with their own lean littermates but not dbmice. LPS reduced serum glucose both oband dbmice corticosterone only Despite very high basal levels dbmice, a twofold increase was observed after littermates. No differences were detected interleukin...
IL-1 plays an important role in the pathophysiologic responses to infection and inflammation, part by mediating its own production that of other proinflammatory cytokines. However, relative contribution alpha beta inflammatory response has not been well clarified. Using beta-deficient (IL-1 -/-) mice, we investigated specific vivo vitro LPS. No differences between +/+ -/- mice were observed circulating levels for alpha, IL-6, or TNF-alpha after systemic administration either a low (5...
Endotoxin [lipopolysaccharide (LPS)], the major antigen of outer membrane Gram-negative bacteria, consists a variable-size carbohydrate chain that is covalently linked to N,O-acylated beta-1,6-D-glucosamine disaccharide 1,4'-bisphosphate (lipid A). The toxic activity LPS resides in lipid A structure. structural features synthetic peptides bind with high affinity, detoxify vitro, and prevent LPS-induced cytokine release lethality vivo were defined. binding thermodynamics comparable an...
Administration of endotoxin (lipopolysaccharide, LPS) induces profound anorexia. Injection leptin decreases food intake in mice. Recently, we reported that LPS and cytokines increase levels hamsters. To further investigate the role LPS-induced anorexia, administered to receptor-deficient (db/db) leptin-deficient (ob/ob) We found caused anorexia both db/db ob/ob As might be predicted if had a mice were somewhat resistant However more sensitive No differences between their respective...
Abstract IL-18-binding protein (IL-18BP) is a natural IL-18 inhibitor. Human IL-18BP isoform was produced as fusion construct with human IgG1 Fc and assessed for binding neutralizing IL-18. IL-18BP-Fc binds human, mouse, rat high affinity (KD 0.3–5 nM) in BIAcore-based assay. In vitro, blocks (100 ng/ml)-induced IFN-γ production by KG1 cells (EC50 = 0.3 μg/ml). mice challenged an LD90 of LPS (15 mg/kg), (5 mg/kg) administered 10 min before protects against lethality. induced ED50 0.005...
Abstract Background IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness. This study investigated multiple-dose pharmacokinetics safety profile human anti-IL-13 antibody (CAT-354) adults with asthma. Methods was a multiple-dose, randomised, double-blind, placebo-controlled phase 1 asthmatics (forced expiratory volume second [FEV ] ≥ 80% predicted). Subjects were randomised to receive three intravenous infusions CAT-354 (1 mg/kg, 5 mg/kg or 10 mg/kg)...
Amplification and overexpression of HER2 (human epidermal growth factor receptor 2), an ErbB2 tyrosine kinase, have been implicated in human cancer metastasis. A bispecific tetravalent anti-HER2 antibody (anti-HER2-Bs), targeting two non-overlapping epitopes on domain IV (trastuzumab) II (39S), has reported to induce rapid internalization efficient degradation receptors. In this study, we investigated the molecular mechanism antibody-induced intracellular trafficking. Using quantitative...
Leptin-deficient ob/ob mice are protected from Con A-induced hepatitis. However, it is unclear whether leptin deficiency or obesity itself responsible for this protection. To address question, wild-type (WT) obese with high serum levels were generated by injection of gold thioglucose (WT GTG). Both A-injected WT and GTG developed hepatitis, whereas no hepatic damage was observed in mice. Moreover, TNF-α IFN-γ as well expression the activation marker CD69 elevated liver mononuclear cells...
To assess the bioavailability and pharmacokinetics of CAT-354, an anti-IL-13 human monoclonal IgG4 antibody, following subcutaneous (s.c.) intravenous (i.v.) administration.This was a single-dose, randomized, open-label, parallel-group study. Healthy male subjects aged 20-54 years were randomly assigned to one three dose groups (n= 10/group) receive CAT-354: 150 mg i.v.; s.c. or 300 (two injections). Serum pharmacokinetics, adverse events (AEs), vital signs, electrocardiograms laboratory...
<p>Elution profiles of zovodotin and vedotin by high-performance liquid chromatography</p>