A5076566919- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- HER2/EGFR in Cancer Research
- Anesthesia and Sedative Agents
- Viral Infections and Outbreaks Research
- Statistical Methods in Clinical Trials
- Immune Cell Function and Interaction
- Drug Transport and Resistance Mechanisms
- COVID-19 Clinical Research Studies
- Influenza Virus Research Studies
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Veterinary Pharmacology and Anesthesia
- Glycosylation and Glycoproteins Research
- Evolution and Genetic Dynamics
- Drug-Induced Hepatotoxicity and Protection
- Rabies epidemiology and control
- Biosimilars and Bioanalytical Methods
- Ovarian cancer diagnosis and treatment
- Bacterial biofilms and quorum sensing
- Sepsis Diagnosis and Treatment
- Antimicrobial Peptides and Activities
- Phagocytosis and Immune Regulation
- Anesthesia and Pain Management
Certara (United States)
2016-2025
Integra LifeSciences (United States)
2020-2025
Strategic Solutions Consulting (United States)
2024
University of Edinburgh
2011-2024
Integra (United States)
2024
Western General Hospital
1998-2023
Deakin University
2022-2023
Inserm
2020
Edinburgh Cancer Research
2005-2019
Amgen (United States)
2014-2016
Abstract Myelin is required for the function of neuronal axons in central nervous system, but mechanisms that support myelin health are unclear. Although macrophages system have been implicated 1 , it unknown which macrophage populations involved and aspects they influence. Here we show resident microglia crucial maintenance adulthood both mice humans. We demonstrate dispensable developmental ensheathment. However, subsequent regulation growth associated cognitive function, preservation...
Soluble species of multimeric amyloid-beta including globular oligomers (AβOs) and linear protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against soluble AβO, that has over 650-fold greater binding affinity for AβOs monomers appears have relatively little amyloid plaque. To assess safety, pharmacokinetics, exploratory measures target engagement, biomarker effects, clinical efficacy sabirnetug in participants with early symptomatic Alzheimer's...
Licensed rabies virus vaccines based on whole inactivated are effective in humans. However, there is a lack of detailed investigations the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses lipid nanoparticle-formulated unmodified mRNA encoding glycoprotein (RABV-G) induces higher levels RABV-G specific plasmablasts T cells blood, plasma bone marrow compared to Rabipur non-human primates. The also generates binding...
1. Administration of frusemide or ethacrynic acid to cephaloridine-treated mice increased both the incidence and extent proximal renal tubular necrosis compared with that obtained in control mice.2. rats produced significant changes urine output, electrolyte excretion proteinuria, plasma urea nitrogen creatinine values were significantly controls received cephaloridine alone.3. Histological examination kidneys showed a higher greater cephaloridine.4. It is suggested this adverse drug...
Summary . The anaesthetic, cardiovascular, respiratory and adverse effects produced by the intravenous injection of CT 1341, thiopentone, methohexitone, pentobarbitone, propanidid ketamine have been compared in unrestrained cats prepared with chronically implanted venous arterial cannulae. Aortic blood pressure heart rates were monitored before, during after loss consciousness. 1341 rapid induction anaesthesia followed moderately recovery, was active over a wide range doses caused minimal...
As new treatment modalities are being explored for SARS-CoV-2, efforts to repurpose existing marketed drugs remain an attractive option, as these agents readily available and have a known safety profile. It is important recognize that not been specifically developed or optimized the of SARS-CoV-2 infected patients. Success in repurposing will depend on mindful first principles around clinical pharmacology dosing strategies, noting dose regimens were different indications. 'Getting right'...
Lisocabtagene maraleucel (liso-cel) is a CD19-directed, defined composition, 4-1BB chimeric antigen receptor (CAR) T-cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells. Large between-subject variability has been noted with CAR therapies; patient characteristics might contribute to expansion variability. We developed population cellular kinetic model characterize the kinetics liso-cel transgene, via quantitative polymerase chain reaction assessment after intravenous...
Objectives: Lymphodepletion (LD) conditioning regimen prior to CAR T-cell therapy treatment has shown play a critical role in success [1-4]. It creates an immunosuppressive environment for engraftment and expansion. Limited optimization of LD is typically performed while evaluating dose levels T-cells Phase 1/2, setting the stage underperformance promising emerging interventions regulatory scrutiny (i.e. Project Optimus) especially allogeneic space when adding alemtuzumab (ALEM) standard...
Abstract Purpose: The aim of this study was to investigate the antitumor effects HER2-directed combination therapy in ovarian cancer xenograft models evaluate their potential. combinations trastuzumab and pertuzumab, aromatase inhibitor were investigated. Experimental Design: trastuzumab, letrozole on growth response, apoptosis, morphology, gene protein expression evaluated SKOV3 cell line a panel five human xenografts derived directly from clinical specimens. Results: antibodies showed...
Trastuzumab and pertuzumab target the Human Epidermal growth factor Receptor 2 (HER2). Combination therapy has been shown to provide enhanced antitumour activity; however, downstream signalling explain how these drugs mediate their response is not clearly understood. Transcriptome profiling was performed after 4 days of trastuzumab, combination treatment in human ovarian cancer vivo. Signalling pathways identified were validated investigated primary xenografts at protein level across a...
Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) relationship of a therapeutic monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) exhibiting target-mediated drug disposition (TMDD) is critical for selecting optimal dosing regimens. We describe PK/PD evolocumab using mathematical model that captures binding removal unbound PCSK9 as well reduction in circulating low-density lipoprotein cholesterol (LDL-C). Data were pooled from 2 clinical studies:...
We hypothesized that viral kinetic modelling could be helpful to prioritize rational drug combinations for COVID-19. The aim of this research was use a cell cycle model SARS-CoV-2 explore the potential impact drugs, or act at different stages in life might have on various metrics infection outcome relevant early COVID-19 disease.
A computer model capable of integrating mechanisms biofilm resistance to disinfection by antimicrobial agents was developed. Resistance considered included retarded penetration due a stoichiometric reaction between the agent and biomass, incomplete catalytic existence fraction cells in resistant phenotypic state. Mathematical models these processes were derived solved simulation package MATLAB. Four sets fitted experimental data on Pseudomonas aeruginosa biofilms fit each three models. No...
Abstract Activation of gonadotropin-releasing hormone (GnRH) receptors inhibits proliferation transformed cells derived from reproductive tissues and in transfected cell lines. Hence, GnRH represent a therapeutic target for direct action analogues on certain proliferating cells. However, more biological data are required to develop this particular application analogues. Therefore, we compared the effects receptor activation HEK293 (HEK293[SCL60]) with human ovarian cancer lines SKOV3 EFO21,...
This study investigated the antitumour effects of two dual mTOR/PI3K inhibitors, gedatolisib (WYE-129587/PKI-587/PF-05212384) and PF-04691502 against a panel six human patient derived ovarian cancer xenograft models. Both inhibitors demonstrated activity all xenografts tested. The compounds produced tumour stasis during treatment period upon cessation treatment, tumours re-grew. In several models, there was an initial rapid reduction volume over first week before stasis. No toxicity observed...
As the global COVID-19 pandemic continues, unabated and clinical trials demonstrate limited effective pharmaceutical interventions, there is a pressing need to accelerate treatment evaluations. Among options for accelerated development evaluation of drug combinations in absence prior monotherapy data. This approach appealing number reasons. First, combining two or more drugs with related complementary therapeutic effects permits multipronged addressing variable pathways disease. Second, if...