Andrew J. Massey

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INTRODUCTION Heat shock protein 90 (HSP90) is a key component of a multichaperone complex involved in the post-translational folding of a large number of client proteins, many of which play essential roles in tumorigenesis. HSP90 has emerged in recent years as a promising new target for anticancer therapies. METHODS The concentrations of the HSP90(More)
The practice of evidence-based veterinary medicine involves the utilisation of scientific evidence for clinical decision making. To enable this, research topics pertinent to clinical practice need to be identified, and veterinary clinicians are best placed to do this. The main aim of this study was to describe the veterinary population, the common species(More)
Chk1 forms a core component of the DNA damage response and small molecule inhibitors are currently being investigated in the clinic as cytotoxic chemotherapy potentiators. Recent evidence suggests that Chk1 inhibitors may demonstrate significant single agent activity in tumors with specific DNA repair defects, a constitutively activated DNA damage response(More)
The thiopurines, 6-thioguanine and 6-mercaptopurine, are antileukemic agents that are incorporated into DNA following retrieval by the purine salvage pathway (see [1] for a review). Their toxicity requires active DNA mismatch repair (MMR), and thiopurine resistance is an acknowledged phenotype of MMR-defective cells [2, 3]. In addition to these direct(More)
Chk1 inhibitors are currently in clinical trials as putative potentiators of cytotoxic chemotherapy drugs. Chk1 inhibitors may exhibit single agent anti-tumor activity in cancers with underlying DNA repair, DNA damage response or DNA replication defects. Here we describe the cellular effects of the pharmacological inhibition of the checkpoint kinase Chk1 by(More)
BACKGROUND Checkpoint kinase 1 and 2 (Chk1/Chk2), and the Aurora kinases play a critical role in the activation of the DNA damage response and mitotic spindle checkpoints. We have identified a novel inhibitor of these kinases and utilized this molecule to probe the functional interplay between these two checkpoints. PRINCIPAL FINDINGS Fragment screening,(More)
Chk1 inhibitors are currently in clinical trials in combination with a range of cytotoxic agents and have the potential to potentiate the clinical activity of a large number of standard of care chemotherapeutic agents. Utilizing pharmacodynamic biomarkers to optimize drug dose and scheduling in these trials could greatly enhance the likelihood of clinical(More)
Access to the most up-to-date evidence is an important cornerstone for veterinarians attempting to practice in an evidence-based manner; therefore, an understanding of what and how information is accessed is vital. The aim of this study was to identify what resources the UK veterinary profession access and regard as most useful. Based on questionnaires(More)
High-content imaging is a powerful tool for determining cell phenotypes at the single cell level. Characterising the effect of small molecules on cell cycle distribution is important for understanding their mechanism of action especially in oncology drug discovery but also for understanding potential toxicology liabilities. Here, a high-throughput(More)
Veterinarians are encouraged to use evidence to inform their practice, but it is unknown what resources (e.g. journals, electronic sources) are accessed by them globally. Understanding the key places veterinarians seek information can inform where new clinically relevant evidence should most effectively be placed. An international survey was conducted to(More)