Outcomes associated with local treatment of nasal planum squamous cell carcinoma in dogs: 89 cases (2003-2020).

Objective: To describe the clinical characteristics, treatments, complications, and outcomes in dogs with nasal planum squamous cell carcinoma (SCC) undergoing local treatment.

Methods: A retrospective, multi-institutional study was performed. Medical records were searched to identify dogs diagnosed with nasal planum SCC.

Effect of glyceryl trinitrate and clevidipine administration on CT angiogram findings in dogs undergoing prostatic artery embolization for prostatic carcinoma.

Objectives: The primary aim of this study was to evaluate the effects of vasodilator administration on CT angiography (CTA) prostatic artery diameter and peak opacification in dogs with prostatic carcinoma prior to prostatic artery embolization (PAE).

Materials And Methods: A prospective clinical trial was performed. Ten dogs with naturally occurring prostatic carcinoma and no evidence of cardiovascular disease were enrolled.

Preclinical evaluation and first-in-dog clinical trials of PBMC-expanded natural killer cells for adoptive immunotherapy in dogs with cancer.

Background: Natural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product.

Treatment of retroperitoneal sarcoma results in improved outcomes.

Objective: To report the clinical characteristics, treatments, and outcomes in a cohort of dogs with histologically confirmed retroperitoneal sarcoma (RPS) and to identify potential variables of prognostic significance.

Animals: 46 client-owned dogs from 10 clinics with histopathologic diagnosis of a sarcoma originating from the retroperitoneal space.

Methods: Medical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes.

Improved characterization and translation of NK cells for canine immunotherapy.

The field of cancer immunology has seen a meteoric rise in interest and application due to the discovery of immunotherapies that target immune cells, often leading to dramatic anti-tumor effects. However, successful cellular immunotherapy for solid tumors remains a challenge, and the application of immunotherapy to dogs with naturally occurring cancers has emerged as a high yield large animal model to bridge the bench-to-bedside challenges of immunotherapies, including those based on natural killer (NK) cells. Here, we review recent developments in the characterization and understanding of canine NK cells, a critical springboard for future translational NK immunotherapy research.

Missing a "Missing Self" Mechanism: Modeling and Detection of Ly49 Expression in Canine NK Cells.

NK cells are a key focus in immuno-oncology, based on their ability to eliminate malignant cells without prior sensitization. Dogs are valuable models for translational immunotherapy studies, especially for NK cells, where critical species differences exist between mice and humans. Given that the mechanism for recognition of "self" by canine NK cells is currently unknown, we sought to evaluate expression of Ly49 in canine NK cells using in silico and high-throughput techniques.

The diagnostic yield of preoperative screening for oral cancer in dogs over 15 years, part 1: locoregional screening.

Objective: Determine locoregional diagnostic yield of 4-site screening (head, neck, chest, and abdomen) to diagnose metastatic disease or clinically significant comorbid diseases in dogs with oral cancer.

Animals: 381 dogs with histologically confirmed oral tumors.

Methods: Medical records from 381 dogs with histologically confirmed oral tumors that underwent preoperative screening were retrospectively reviewed.

A variant in the 5'UTR of ERBB4 is associated with lifespan in Golden Retrievers.

Genome-wide association studies (GWAS) in long-lived human populations have led to identification of variants associated with Alzheimer's disease and cardiovascular disease, the latter being the most common cause of mortality in people worldwide. In contrast, naturally occurring cancer represents the leading cause of death in pet dogs, and specific breeds like the Golden Retriever (GR) carry up to a 65% cancer-related death rate. We hypothesized that GWAS of long-lived GRs might lead to the identification of genetic variants capable of modifying longevity within this cancer-predisposed breed.

The diagnostic yield of preoperative screening for oral cancer in dogs over 15 years, part 2: distant screening.

Objective: Determine diagnostic yield of chest, abdomen, and 4-site screening to diagnose metastatic disease and secondary diseases of prognostic significance in dogs with oral cancer.

Sample: Medical records from 381 dogs with histologically confirmed oral tumors that underwent preoperative screening were retrospectively reviewed.

Results: Thoracic metastasis was diagnosed in 4.

Efficacy and toxicity of carboplatin in the treatment of macroscopic mesenchymal neoplasia in dogs.

Palliative chemotherapy options for dogs with macroscopic non-osseous mesenchymal tumours are limited. The purpose of this study was to assess the response rate of these tumours to carboplatin chemotherapy. Medical records of 28 dogs treated with carboplatin for macroscopic mesenchymal neoplasia between 1990 and 2022 were retrospectively reviewed.

High-Grade, Stage 2 Mast Cell Tumors: Outcome in Dogs With Local and Systemic Therapy.

Canine mast cell tumors (MCTs) have highly variable clinical behavior, and predicting outcomes in individual dogs remains challenging. Many studies combine dogs with varying tumor grades, clinical stage, or treatments, confounding those results. The purpose of this retrospective study was to determine outcome and prognostic factors in a specific subset of dogs with high-grade, stage 2, cutaneous MCTs treated with adequate local control via surgery with or without radiation therapy and adjuvant cytotoxic chemotherapy.

Longevity and mortality in cats: A single institution necropsy study of 3108 cases (1989-2019).

Client-owned cats who underwent a post-mortem examination (n = 3,108) at a veterinary medical teaching hospital between 1989 and 2019 were studied to determine longevity and factors affecting mortality. Demographic factors, environmental factors, age, and causes of death were assessed. Sexes included 5.

MRI characteristics of canine prostatic neoplasia.

Magnetic resonance imaging (MRI) has been used to evaluate dogs with suspected prostatic neoplasia, however, published studies describing MRI characteristics of canine prostatic neoplasia are currently lacking. The aims of the current retrospective case series study were to describe MRI findings of the pelvic region in dogs with a histopathologic or cytologic diagnosis of prostatic neoplasia. Retrospective analysis of these images was then performed by a board-certified veterinary radiologist for shared imaging characteristics.

Fractionated oral dosing and its effect on cyclophosphamide pharmacokinetics in dogs with high-grade multicentric lymphoma.

Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days.

Using the canine microbiome to bridge translation of cancer immunotherapy from pre-clinical murine models to human clinical trials.

The microbiome has clearly been established as a cutting-edge field in tumor immunology and immunotherapy. Growing evidence supports the role of the microbiome in immune surveillance, self-tolerance, and response to immune checkpoint inhibitors such as anti PD-L1 and CTLA-4 blockade (1-6). Moreover, recent studies including those using fecal microbial transplantation (FMT) have demonstrated that response to checkpoint immunotherapies may be conferred or eliminated through gut microbiome modulation (7, 8).

Recent, full-length gene retrocopies are common in canids.

Gene retrocopies arise from the reverse transcription and insertion into the genome of processed mRNA transcripts. Although many retrocopies have acquired mutations that render them functionally inactive, most mammals retain active LINE-1 sequences capable of producing new retrocopies. New retrocopies, referred to as retro copy number variants (retroCNVs), may not be identified by standard variant calling techniques in high-throughput sequencing data.

Evaluation of the use of a novel bioabsorbable polymer drug-eluting microsphere for transarterial embolization of hepatocellular neoplasia in dogs.

In dogs with non-resectable hepatic neoplasia, treatment options are limited. The objectives of this study were to describe the use of a novel drug-eluting embolic microsphere containing paclitaxel for use during transarterial chemoembolization (TACE), to compare results of liver-specific owner questionnaires and tumor volume pre- and post-TACE, and to measure systemic paclitaxel concentration post-TACE. Client-owned dogs with non-resectable hepatic neoplasia were prospectively enrolled.

Transcriptome Analysis of Tumor-Infiltrating Lymphocytes Identifies NK Cell Gene Signatures Associated With Lymphocyte Infiltration and Survival in Soft Tissue Sarcomas.

Purpose: Clinical successes using current T-cell based immunotherapies have been limited in soft tissue sarcomas (STS), while pre-clinical studies have shown evidence of natural killer (NK) cell activity. Since tumor immune infiltration, especially tumor-infiltrating lymphocytes, is associated with improved survival in most solid tumors, we sought to evaluate the gene expression profile of tumor and blood NK and T cells, as well as tumor cells, with the goal of identifying potential novel immune targets in STS.

Experimental Design: Using fluorescence-activated cell sorting, we isolated blood and tumor-infiltrating CD3CD56 NK and CD3 T cells and CD45 viable tumor cells from STS patients undergoing surgery.

Expression and therapeutic targeting of BMI1 in canine gliomas.

The BMI1 proto-oncogene, polycomb ring finger protein (BMI1) is a key component of the epigenetic polycomb repressor complex 1, and has been associated with aggressive behaviour and chemotherapeutic resistance in various malignances including human gliomas. Similar to humans, spontaneous canine gliomas carry a poor prognosis with limited therapeutic options. BMI1 expression and the effects of BMI1 inhibition have not been evaluated in canine gliomas.

Inhaled recombinant human IL-15 in dogs with naturally occurring pulmonary metastases from osteosarcoma or melanoma: a phase 1 study of clinical activity and correlates of response.

Purpose: Although recombinant human interleukin-15 (rhIL-15) has generated much excitement as an immunotherapeutic agent for cancer, activity in human clinical trials has been modest to date, in part due to the risks of toxicity with significant dose escalation. Since pulmonary metastases are a major site of distant failure in human and dog cancers, we sought to investigate inhaled rhIL-15 in dogs with naturally occurring lung metastases from osteosarcoma (OSA) or melanoma. We hypothesized a favorable benefit/risk profile given the concentrated delivery to the lungs with decreased systemic exposure.

Expression of the hedgehog signalling pathway and the effect of inhibition at the level of smoothened in canine osteosarcoma cell lines.

Osteosarcoma (OSA) is the most common malignant bone cancer in dogs. Canine and human OSA share several features, including tumour environments, response to traditional treatment, and several molecular pathways. Hedgehog (Hh) signalling is known to contribute to tumorigenesis and progression of various cancers, including human OSA.

Retrospective immunohistochemical investigation of suspected non-visceral leiomyosarcoma in dogs.

Visceral leiomyosarcoma is well described in dogs, but information about non-visceral locations and prevalence is lacking. The diagnosis of leiomyosarcoma is challenging without a gold standard, and often includes the use of immunohistochemical (IHC) stains. We used defined histopathologic patterns, histochemical staining, and IHC staining for smooth muscle actin (SMA), desmin, and laminin to characterize suspected non-visceral leiomyosarcoma in dogs at a single academic institution.

G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells.

Background: The use of fenbendazole (FBZ) in terminal cancer patients has recently increased, as anthelminthic drugs, such as FBZ and benzimidazole, exhibit anti-tubulin effects in tumour cells.

Objectives: The present study evaluated the in vitro anti-cancer effects of FBZ in five canine melanoma cell lines originating from the oral cavity (UCDK9M3, UCDK9M4, UCDK9M5, KMeC and LMeC).

Methods: Five canine melanoma cell lines were treated with FBZ and analysed with cell viability assay, cell cycle analysis, western blot assay and immunofluorescence staining to identify apoptotic effect, cell cycle arrest, microtubule disruption and mitotic slippage.

T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma.

Investigation of canine T cell immunophenotypes in canine melanomas as prognostic biomarkers for disease progression or predictive biomarkers for targeted immunotherapeutics remains in preliminary stages. We aimed to examine T cell phenotypes and function in peripheral blood mononuclear cells (PBMC) and baseline tumor samples by flow cytometry, and to compare patient ( = 11-20) T cell phenotypes with healthy controls dogs ( = 10-20). CD3, CD4, CD8, CD25, FoxP3, Ki67, granzyme B, and interferon-γ (IFN-γ) were used to classify T cell subsets in resting and mitogen stimulated PBMCs.

Natural Killer and T Cell Infiltration in Canine Osteosarcoma: Clinical Implications and Translational Relevance.

Metastatic osteosarcoma has a bleak prognosis in both humans and dogs, and there have been minimal therapeutic advances in recent decades to improve outcomes. Naturally occurring osteosarcoma in dogs is shown to be a highly suitable model for human osteosarcoma, and limited data suggest the similarities between species extend into immune responses to cancer. Studies show that immune infiltrates in canine osteosarcoma resemble those of human osteosarcoma, and the analysis of tumor immune constituents as predictors of therapeutic response is a promising direction for future research.