The EphA2 Receptor Regulates Invasiveness and Drug Sensitivity in Canine and Human Osteosarcoma Cells.

Osteosarcoma is an aggressive bone cancer affecting both humans and dogs, often leading to pulmonary metastasis. Despite surgery and chemotherapy being the primary treatment modalities, survival rates remain low in both species, underscoring the urgent need for more efficacious therapeutic options. Accumulating evidence indicates numerous biological and clinical similarities between human and canine osteosarcoma, making it an ideal choice for comparative oncological research that should benefit both species.

Retrospective analysis of carboplatin-induced cumulative neutropenia in cancer-bearing dogs.

Objective: To determine the clinical significance of performing repeated postchemotherapy CBC for cancer-bearing dogs receiving ≥ 4 carboplatin treatments. The secondary aim was to identify risk factors associated with cumulative carboplatin-induced neutropenia in those dogs.

Animals: 40 client-owned dogs diagnosed with cancer.

Image-Based Dosimetry in Dogs and Cross-Reactivity with Human Tissues of IGF2R-Targeting Human Antibody.

Background: Osteosarcoma (OS) represents the most common primary bone tumor in humans and in companion dogs, being practically phenotypically identical. There is a need for effective treatments to extend the survival of patients with OS. Here, we examine the dosimetry in beagle dogs and cross-reactivity with human tissues of a novel human antibody, IF3, that targets the insulin growth factor receptor type 2 (IGF2R), which is overexpressed on OS cells, making it a candidate for radioimmunotherapy of OS.

Characterization of IGF2R Molecular Expression in Canine Osteosarcoma as Part of a Novel Comparative Oncology Approach.

Progress in prognostic factors, treatments, and outcome for both canine and human osteosarcoma (OS) has been minimal over the last three decades. Surface overexpression of the cation independent mannose-6-phosphate/insulin-like growth factor receptor type 2 (IGF2R) has been proven to occur in human OS cells. Subsequently, radioimmunotherapy (RIT) targeting IGF2R has demonstrated promising preliminary results.

Risk factors for appendicular osteosarcoma occurrence in large and giant breed dogs in western Canada.

Objective: Risk factors for the development of canine appendicular osteosarcoma (OSA) have been investigated in numerous studies, but with contradictory results. The aim of this study was to analyze weight, age, breed, sex, neuter status, body condition score, and previous lameness in a population of large and giant breed dogs in western Canada with and without appendicular OSA.

Animals And Procedure: Medical records of 227 large or giant breed dogs diagnosed with appendicular OSA were compared to records from a control population of 454 large and giant breed dogs from the years 2000 to 2020.

Activation of the Anaphase Promoting Complex Reverses Multiple Drug Resistant Cancer in a Canine Model of Multiple Drug Resistant Lymphoma.

Like humans, canine lymphomas are treated by chemotherapy cocktails and frequently develop multiple drug resistance (MDR). Their shortened clinical timelines and tumor accessibility make canines excellent models to study MDR mechanisms. Insulin-sensitizers have been shown to reduce the incidence of cancer in humans prescribed them, and we previously demonstrated that they also reverse and delay MDR development in vitro.

Incidence of Sterile Hemorrhagic Cystitis in Dogs Treated with Cyclophosphamide and Low-Dose Furosemide.

Cyclophosphamide is a commonly used chemotherapy in the treatment of lymphoma. It can cause sterile hemorrhagic cystitis (SHC), and furosemide is used to decrease the incidence of SHC. The aim of this study is to evaluate the incidence of SHC in dogs treated with a bolus maximum tolerated dose of oral cyclophosphamide and oral furosemide at a dose of 1 mg/kg.

Radioimmunotherapy Targeting IGF2R on Canine-Patient-Derived Osteosarcoma Tumors in Mice and Radiation Dosimetry in Canine and Pediatric Models.

Background: Osteosarcoma (OS) has an overall patient survival rate of ~70% with no significant improvements in the last two decades, and novel effective treatments are needed. OS in companion dogs is phenotypically close to human OS, which makes a comparative oncology approach to developing new treatments for OS very attractive. We have recently created a novel human antibody, IF3 to IGF2R, which binds to this receptor on both human and canine OS tumors.

Novel Human Antibodies to Insulin Growth Factor 2 Receptor (IGF2R) for Radioimmunoimaging and Therapy of Canine and Human Osteosarcoma.

Etiological and genetic drivers of osteosarcoma (OS) are not well studied and vary from one tumor to another; making it challenging to pursue conventional targeted therapy. Recent studies have shown that cation independent mannose-6-phosphate/insulin-like growth factor-2 receptor (IGF2R) is consistently overexpressed in almost all of standard and patient-derived OS cell lines, making it an ideal therapeutic target for development of antibody-based drugs. Monoclonal antibodies, targeting IGF2R, can be conjugated with alpha- or beta-emitter radionuclides to deliver cytocidal doses of radiation to target IGF2R expression in OS.

Assessment of neutrophil function in canine cancer patients undergoing chemotherapy and correlation with neutrophil numbers.

Decreased neutrophil function following administration of chemotherapy has been reported in dogs with lymphoma. The first objective of our study was to determine if neutrophil oxidative burst and phagocytic activity are affected by chemotherapy 7 to 10 days following initiation of treatment in dogs with lymphoma and non-lymphoma malignancies. The second objective was to determine if there is a correlation between neutrophil numbers and neutrophil function before or after initiation of chemotherapy.

Prevalence and Prognostic Impact of Papillomavirus Type 2 Infection in Equine Squamous Cell Carcinomas in Western Canadian Horses.

papillomavirus type-2 (EcPV-2) has been proposed as a causal factor in equine genital squamous cell carcinoma (SCC). This study had 2 objectives: first, calculate the frequency of papillomavirus (PV) and EcPV-2 infection in papillomas, carcinomas in situ (CIS), and SCCs in Western Canadian horses; and second, determine if EcPV-2 status of equine SCCs is associated with overall survival (OS). EcPV-2 status of 115 archived tissue samples, spanning 6 years, was determined using broad spectrum (MY09/11) and EcPV-2-specific polymerase chain reaction (PCR) assays, EcPV-2-E6/E7 chromogenic RNA in situ hybridization (R-ISH), and amplicon sequencing.

Marginal zone lymphoma in a dog.

A 13-year-old spayed female American Cocker Spaniel was presented for evaluation of a cough and weight loss. Physical exam revealed generalized lymphadenopathy. The patient was diagnosed with marginal zone lymphoma (MZL) on histopathology of an extirpated lymph node.

Extraskeletal osteosarcoma associated with a benign hair follicle tumor in a dog.

A rare presentation of an extraskeletal osteosarcoma, suspected to have evolved from chronic inflammation associated with a benign hair follicle tumor in a dog is described. The patient was treated with surgical excision, carboplatin, and toceranib. The patient had an extended disease-free interval and a survival time of 45.

Detection and targeting insulin growth factor receptor type 2 (IGF2R) in osteosarcoma PDX in mouse models and in canine osteosarcoma tumors.

Osteosarcoma (OS) represents 3.4% of all childhood cancers with overall survival of 70% not improving in 30 years. The consistent surface overexpression of insulin-like growth factor-2 receptor (IGF2R) has been reported in commercial and patient-derived xenograft (PDX) OS cell lines.

Evaluation of lymph node aspirates at diagnosis and relapse in dogs with high-grade multicentric lymphoma and comparison with survival time.

Background: Canine high-grade multicentric lymphoma, a common disease with variable response to chemotherapy, is often diagnosed using cytology.

Objectives: The purpose of the study was to compare cytologic features of canine peripheral lymph node aspirates collected at diagnosis and at relapse, and evaluate their usefulness in predicting survival.

Methods: Cytologic scoring based on a rubric and nuclear morphometry analyses were performed on cytologic smears collected at diagnosis and at relapse.

Increase in gene-transcript levels as indicators of up-regulation of the unfolded protein response in spontaneous canine tumors.

The unfolded protein response (UPR), a conserved cellular response to stressors such as hypoxia and nutrient deprivation, is associated with angiogenesis and metastasis in tumor cells. This article discusses a pilot study conducted to determine whether components of the UPR could be identified in spontaneous canine tumors and whether they were up-regulated within tumor tissue compared with adjacent normal tissue. Tissue samples of various spontaneous canine neoplasms were taken from 13 dogs shortly after surgical excision or euthanasia; control samples were taken from adjacent normal tissue.