Population Pharmacokinetics, Pharmacodynamics and Safety Properties of Trametinib in Dogs With Cancer: A Phase I Dose Escalating Clinical Trial.

MAPK has been reported as a key oncogenic pathway for canine histiocytic sarcoma, which can be pharmacologically targeted with trametinib, a small inhibitor of MEK1/2. Preliminary data showed promising antitumor activity in in vitro and in vivo models and represented a proof of concept to translate the findings from bench to bedside. In this phase I, dose escalating study using a 3 + 3 cohort design, trametinib was evaluated in 18 dogs with cancer.

Identification of a Hypomorphic Variant in Bernese Mountain Dogs.

Bernese mountain dogs (BMDs), have an overall cancer incidence of 50%, half of which is comprised of an otherwise rare tumor, histiocytic sarcoma (HS). While recent studies have identified driver mutations in the MAPK pathway, identification of key predisposing genes has been elusive. Studies have identified several loci to be associated with predisposition to HS in BMDs, including near the region, but no causative coding variant has been identified.

Development of a 17-Plex of Penta- and Tetra-Nucleotide Microsatellites for DNA Profiling and Paternity Testing in Horses.

Tetranucleotide and pentanucleotide short tandem repeat (hereafter termed tetraSTR and pentaSTR) polymorphisms have properties that make them desirable for DNA profiling and paternity testing. However, certain species, such as the horse, have far fewer tetraSTRs than other species and for this reason dinucleotide STRs (diSTRs) have become the standard for DNA profiling in horses, despite being less desirable for technical reasons. During our testing of a series of candidate genes as potentially underlying a heritable condition characterized by megaesophagus in the Friesian horse breed, we found that good tetraSTRs do exist in horses but, as expected, at a much lower frequency than in other species, e.

Angiostrongylus cantonensis in a Red Ruffed Lemur at a Zoo, Louisiana, USA.

A red ruffed lemur (Varecia rubra) from a zoo in Louisiana, USA, was euthanized for worsening paresis. Brain and spinal cord histology identified eosinophilic meningoencephalomyelitis with intralesional adult Angiostrongylus sp. nematodes.

Expression of Carboxypeptidase A3 and Tryptase as Markers for Lymph Node Metastasis of Canine Cutaneous Mast Cell Tumors.

Detection of metastatic mast cell tumors (MCTs) in lymph nodes is a critical factor for treatment, prognosis, and clinical management. Presence/absence of mast cells in the lymph nodes cannot be used as a sole parameter to determine metastasis due to the inability to differentiate neoplastic from non-neoplastic/inflammatory mast cells. While cytologic and histopathologic classifications for assessment of metastatic MCTs based on the numbers and distribution of mast cells have been developed, inconsistency between the clinical interpretation of these grading schemes and actual metastatic status occurs.