The human ABCB1 protein, (P-glycoprotein or MDR1) is a membrane-bound glycoprotein that harnesses the energy of ATP hydrolysis to drive the unidirectional transport of substrates from the cytoplasm to the extracellular space. As a large range of therapeutic agents are known substrates of ABCB1 protein, its role in the onset of multidrug resistance has been the focus of much research. This role has been of particular interest in the field of pharmacogenomics where genetic variation within the ABCB1 gene, particularly in the form of single nucleotide polymorphisms (SNPs), is believed to contribute to inter-individual variation in ABCB1 function and drug response. In this review we provide an update on the influence of coding region SNPs within the ABCB1 gene on drug pharmacokinetics. By utilizing the crystal structure of the mouse ABCB1 homolog (Abcb1a), which is 87% homologous to the human sequence, we accompany this discussion with a graphical representation of residue location for amino acids corresponding to human ABCB1 coding region SNPs. Also, an assessment of residue conservation, which is calculated following multiple sequence alignment of 11 confirmed sequences of ABCB1 homologs, is presented and discussed. Superimposing a 'heat map' of residue homology to the Abcb1a crystal structure has permitted additional insights into both the conservation of individual residues and the conservation of their immediate surroundings. Such graphical representation of residue location and conservation supplements this update of ABCB1 pharmacogenetics to help clarify the often confounding reports on the influence of ABCB1 polymorphisms on drug pharmacokinetics and response.

Cancer cells possess unique characteristics such as invasiveness, the ability to undergo epithelial-mesenchymal transition, and an inherent stemness. Cell morphology is altered during these processes and this is highly dependent on actin cytoskeleton remodeling. Regulation of the actin cytoskeleton is, therefore, important for determination of cell fate. Mutations within the TP53 (tumor suppressor p53) gene leading to loss or gain of function (GOF) of the protein are often observed in aggressive cancer cells. Here, we highlight the roles of p53 and its GOF mutants in cancer cell invasion from the perspective of the actin cytoskeleton; in particular its reorganization and regulation by cell adhesion molecules such as integrins and cadherins. We emphasize the multiple functions of p53 in the regulation of actin cytoskeleton remodeling in response to the extracellular microenvironment, and oncogene activation. Such an approach provides a new perspective in the consideration of novel targets for anti-cancer therapy.

Our findings specifically highlight the topoisomerase poison 9-amino-DACA, its 5-methylsulphone derivative, AS-DACA, and the bis(phenazine-1-carboxamide) transcription inhibitor MLN944/XR5944, currently in phase I trial, as candidates for further research into new agents for the treatment of RMS.

Knowledge of the most common presenting complaints and diagnoses in companion animals is valuable in preparing veterinary students and veterinarians to manage the most frequently observed conditions in clinical practice. Pet insurance databases provide access to large sample populations and have been previously used to describe disease incidence in companion animals. The aim of this study was to determine the incidence of presenting complaints and diagnoses in insured Australian dogs through the use of a pet insurance database. Analysis of a de‐identified dataset containing pet insurance claims associated with presenting complaints and diagnoses from 488,472 insured Australian dogs insured in the years 2016 and 2017, was performed. Annual incidence rates of presenting complaints and diagnoses were calculated and expressed as, number of events per 1,000 dog years at risk. The presenting complaints with the highest incidence were vomiting (14.21 events per 1,000 dog years at risk in 2016, 15.80 events per 1,000 dog years at risk in 2017) and pruritus (8.79 events per 1,000 dog years at risk in 2016, 10.30 events per 1,000 dog years at risk in 2017). Presenting complaints affecting the gastrointestinal system were the most common (19.20 events per 1,000 dog years at risk in 2016, 20.77 events per 1,000 dog years at risk in 2017). The diagnoses with the highest incidence were otitis externa (34.12 events per 1,000 dog years at risk in 2016, 34.82 events per 1,000 dog years at risk in 2017) and dermatitis (28.05 events per 1,000 dog years at risk in 2016, 29.99 events per 1,000 dog years at risk in 2017). Diagnoses affecting the integument were the most common (216.56 events per 1,000 dog years at risk in 2016, 219.06 events per 1,000 dog years at risk in 2017). The results from this study can aid in the design of relevant veterinary curricula and may be helpful in prioritising research on common clinical conditions.