PD-1 interactome in osteosarcoma: identification of a novel PD-1/AXL interaction conserved between humans and dogs.

The PD-1/PDL-1 immune checkpoint inhibitors revolutionized cancer treatment, yet osteosarcoma remains a therapeutic challenge. In some types of cancer, PD-1 receptor is not solely expressed by immune cells but also by cancer cells, acting either as a tumor suppressor or promoter. While well-characterized in immune cells, little is known about the role and interactome of the PD-1 pathway in cancer.

Candidate circulating microRNA biomarkers in dogs with chronic pancreatitis.

Background: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis.

Hypothesis: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers.

Use of multi-color flow cytometry for canine immune cell characterization in cancer.

Although immunotherapy is becoming a standard approach of human cancer treatment, only a small but critical fraction of patients responds to the therapy. It is therefore required to determine the sub-populations of patients who will respond to immunotherapies along with developing novel strategies to improve efficacy of anti-tumor immune reactions. Current development of novel immunotherapies relies heavily on mouse models of cancer.

The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I-Associated Peptides.

Tumor antigens can emerge through multiple mechanisms, including translation of noncoding genomic regions. This noncanonical category of tumor antigens has recently gained attention; however, our understanding of how they recur within and between cancer types is still in its infancy. Therefore, we developed a proteogenomic pipeline based on deep learning de novo mass spectrometry (MS) to enable the discovery of noncanonical MHC class I-associated peptides (ncMAP) from noncoding regions.

TGF-β-induced PI3K/AKT/mTOR pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease.

PI3K/AKT/mTOR signalling contributes to several cardiovascular disorders. The aim of this study was to examine the PI3K/AKT/mTOR pathway in myxomatous mitral valve disease (MMVD). Double-immunofluorescence examined expression of PI3K and TGF-β1 in canine valves.

Development of Monoclonal Antibodies Targeting Canine PD-L1 and PD-1 and Their Clinical Relevance in Canine Apocrine Gland Anal Sac Adenocarcinoma.

Canine apocrine gland anal sac adenocarcinoma (AGASACA) is an aggressive canine tumor originating from the anal sac glands. Surgical resection, with or without adjuvant chemotherapy, represents the standard of care for this tumor, but the outcome is generally poor, particularly for tumors diagnosed at an advanced stage. For this reason, novel treatment options are warranted, and a few recent reports have suggested the activation of the immune checkpoint axis in canine AGASACA.

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.

Design, synthesis and biological evaluation of PD-1 derived peptides as inhibitors of PD-1/PD-L1 complex formation for cancer therapy.

Over the past few years, many molecules such as monoclonal antibodies, affibodies, nanobodies, and small compounds have been designed and tested as inhibitors of PD-1/PD-L1 complex formation. Some of them have been successfully implemented into clinical oncology practice. However, the majority of these compounds have disadvantages and limitations, such as high production price, potential for immunogenicity and/or prolonged clearance.

A simplified CT-volumetry method for the canine liver.

Computed tomographic (CT) liver volumetry using the slice addition technique is an accurate, but a time-consuming method. Commonly used DICOM-viewing software only allows contouring of one area per image, which can be troublesome in the transverse plane as different lobes are separated. In this prospective, experimental, methods comparison study, we aimed to determine if hepatic contouring using sagittal reformatting and a reduced number of images would yield accurate results.

Four-dimensional CT excretory urography is an accurate technique for diagnosis of canine ureteral ectopia.

Computed tomographic (CT) excretory urography is commonly used to investigate canine ureteral ectopia (UE). Modern technology allows time-resolved CT imaging (four-dimensional CT excretory urography [4D-CTEU]) over a distance exceeding the detector collimation. Objectives of this prospective, observational, diagnostic accuracy study were to evaluate the diagnostic accuracy of CT excretory urography (CTEU) and 4D-CTEU for UE in dogs with lower urinary tract signs, assess the influence of pelvis positioning, and to determine the significance of the ureterovesical junction (UVJ) angle for UE diagnosis.

Hydrogen deuterium exchange mass spectrometry identifies the dominant paratope in CD20 antigen binding to the NCD1.2 monoclonal antibody.

A comparative canine-human therapeutics model is being developed in B-cell lymphoma through the generation of a hybridoma cell that produces a murine monoclonal antibody specific for canine CD20. The hybridoma cell produces two light chains, light chain-3, and light chain-7. However, the contribution of either light chain to the authentic full-length hybridoma derived IgG is undefined.

CT features of feline lipiduria and renal cortical lipid deposition.

Objectives: The aims of this study were to document the presence and prevalence of feline lipiduria and renal lipid deposition on CT, and to search for associations between the presence of lipiduria and sex, urinary tract abnormalities and urolithiasis.

Methods: The CT examinations of 252 cats were reviewed for the presence of an antigravitational hypodense bubble in the urinary bladder with density values between -180 Hounsfield units (HU) and -20 HU. To identify associations between lipiduria and sex, urinary tract abnormalities and urolithiasis, Fisher's exact test was used.

Hyperprogression Under Immune Checkpoint-Based Immunotherapy-Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model.

Immune evasion is a major challenge for the development of successful cancer treatments. One of the known mechanisms is the expression of immune checkpoints (ICs)-proteins regulating the immune cells activation. The advent of immunotherapy using monoclonal antibodies (mAbs) to block the immune checkpoint receptor-ligand interaction brought about a landslide improvement in the treatment responses, leading to a prompt approval of such therapeutics.

Investigation of novel chemotherapeutics for feline oral squamous cell carcinoma.

Feline oral squamous cell carcinomas (FOSCC) are highly aggressive neoplasms with short survival times despite multimodal treatment. FOSCC are similar to squamous cell carcinomas of the head and neck (SCCHN) in humans, which also present therapeutic challenges. The current study was undertaken to identify novel chemotherapeutics using FOSCC cell lines.

A novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies.

Background: Histiocytic sarcoma is a rare disorder in humans, however it is seen with appreciable frequency in certain breeds of dogs, such as Bernese mountain dog. The purpose of this study was to fully characterize a novel canine histiocytic sarcoma cell line, and utilize it as a tool to screen for potential therapeutic drugs.

Methods: The histiocytic sarcoma cell line was characterized by expression of cellular markers as determined by immunohistochemistry and flow cytometry techniques.

Evaluation of Immunomodulatory Properties of Feline Mesenchymal Stem Cells.

Mesenchymal stem cells (MSC) offer a novel approach to treatment of inflammatory disorders in humans and companion animals. Cats spontaneously develop a wide variety of inflammatory disorders and may potentially benefit from MSC-based therapies. Multiple genes are involved in immunomodulation by MSC and interspecies differences between expressions of these genes exist.

Microcomputed Tomography of Nanocrystal-Doped Tissue Engineered Scaffolds.

Tissue engineered scaffolds (TES) hold promise for improving the outcome of cell-based therapeutic strategies for a variety of biomedical scenarios, including musculoskeletal injuries, soft tissue repair, and spinal cord injury. Key to TES research and development, and clinical use, is the ability to longitudinally monitor TES location, orientation, integrity, and microstructure following implantation. Here, we describe a strategy for using microcomputed tomography (microCT) to visualize TES following implantation into mice.

Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography.

Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive.