Establishment and characterization of two novel patient-derived lines from canine high-grade glioma.

High-grade glioma is an aggressive cancer that occurs naturally in pet dogs. Canine high-grade glioma (cHGG) is treated with radiation, chemotherapy or surgery, but has no curative treatment. Within the past eight years, there have been advances in our imaging and histopathology standards as well as genetic charactereization of cHGG.

Meningioma with rhabdoid features: Pathologic findings in dogs.

Rhabdoid meningioma is a rare type of meningeal neoplasm in humans. This study reports the clinical, pathological, and ultrastructural features of 4 cases of canine meningioma with rhabdoid features. The cases were female and 8 to 12 years of age.

Prognostic histopathologic features of canine glial tumors.

Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain tumors. Hitherto, there is relatively little prognostic data for canine gliomas and none on outcome related to specific histological features. Histologic sections of tumor biopsies from 33 dogs with glioma treated with surgical resection and immunotherapy and 21 whole brains obtained postmortem were reviewed.

CD200 Immune-Checkpoint Peptide Elicits an Anti-glioma Response Through the DAP10 Signaling Pathway.

Numerous therapies aimed at driving an effective anti-glioma response have been employed over the last decade; nevertheless, survival outcomes for patients remain dismal. This may be due to the expression of immune-checkpoint ligands such as PD-L1 by glioblastoma (GBM) cells which interact with their respective receptors on tumor-infiltrating effector T cells curtailing the activation of anti-GBM CD8 T cell-mediated responses. Therefore, a combinatorial regimen to abolish immunosuppression would provide a powerful therapeutic approach against GBM.

Oligodendroglioma with Neuronal Differentiation in Two Boxer Dogs.

Two cases of high-grade glioma comprising sheets of oligodendroglial cells multifocally disrupted by regions of remarkable neuronal differentiation are described. These tumours morphologically resemble 'oligodendroglioma with ganglioglioma-like maturation', a rare tumour of man, but appear to be phenotypically more aggressive. Neuronal markers (synaptophysin, neuron-specific enolase and βIII-tubulin) effectively highlight neuronal elements within these tumours and could potentially help to further investigate the prevalence and biological significance of neuronal differentiation in canine oligodendroglioma.

CD200 Checkpoint Reversal: A Novel Approach to Immunotherapy.

Purpose: Advances in immunotherapy have revolutionized care for some patients with cancer. However, current checkpoint inhibitors are associated with significant toxicity and yield poor responses for patients with central nervous system tumors, calling into question whether cancer immunotherapy can be applied to glioblastoma multiforme. We determined that targeting the CD200 activation receptors (CD200AR) of the CD200 checkpoint with a peptide inhibitor (CD200AR-L) overcomes tumor-induced immunosuppression.

Development of a Novel Canine Model of Ischemic Stroke: Skull Base Approach with Transient Middle Cerebral Artery Occlusion.

Objective: Although canine stroke models have several intrinsic advantages, establishing consistent and reproducible territorial stroke in these models has been challenging because of the abundance of collateral circulation. We have described a skull-base surgical approach that yields reproducible stroke volumes.

Methods: Ten male beagles were studied.

Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma.

Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint protein, CD200, enhanced the capacity of antigen-presenting cells to prime T-cells to mediate an anti-glioma response.

Incidence of and risk factors for major complications or death in dogs undergoing cytoreductive surgery for treatment of suspected primary intracranial masses.

OBJECTIVE To determine incidence of and risk factors for major complications occurring in dogs within 30 days after cytoreductive surgery performed by a single pair of surgeons for treatment of suspected primary intracranial masses. DESIGN Retrospective cohort study. ANIMALS 160 client-owned dogs that underwent cytoreductive surgery for treatment of suspected primary intracranial masses between January 2009 and December 2015 at a veterinary teaching hospital.

Genetically engineered minipigs model the major clinical features of human neurofibromatosis type 1.

Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in (). NF1 patients present with a variety of clinical manifestations and are predisposed to cancer development. Many NF1 animal models have been developed, yet none display the spectrum of disease seen in patients and the translational impact of these models has been limited.

Naturally Occurring Canine Glioma as a Model for Novel Therapeutics.

Background: Current animal models of glioma are limited to small animal models, which are less predictive of treatment of human disease. Canines often develop gliomas de novo, but the natural history of the disease is not well described.

Objective: We provide data for naturally occurring canine gliomas; evaluating medical and surgical therapies.

Association of magnetic resonance imaging-based preoperative tumor volume with postsurgical survival time in dogs with primary intracranial glioma.

OBJECTIVE To assess the relationship between preoperative volume of primary intracranial gliomas in dogs as determined via MRI and survival time after surgical debulking and adjunctive immunotherapy. DESIGN Retrospective cohort study. ANIMALS 47 client-owned dogs enrolled in clinical trials regarding glioma treatments.

Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients.

On September 14-15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings.

Comparison of visual metric and planimetry methods for brain tumor measurement in dogs.

OBJECTIVE To compare the orthogonal diameter (visual metric) method against a manual perimeter tracing (planimetry) method to measure volume of brain tumors in dogs by use of MRI scans. SAMPLE 22 sets of MRI brain scans pertaining to 22 client-owned dogs with histologically confirmed glioma. PROCEDURES MRI scans were reviewed by 2 operators, and scans revealing tumors with a degree of gadolinium enhancement that allowed discrimination between tumor tissue and healthy parenchyma were used.

CD8⁺ T Cell-Independent Immune-Mediated Mechanisms of Anti-Tumor Activity.

Despite the growing number of preclinical and clinical trials focused on immunotherapy for the treatment of malignant gliomas, the prognosis for this disease remains grim. Cancer immunotherapy seeks to recruit an effective immune response to eliminate tumor cells. To date, cancer vaccines have shown only limited effectiveness because of our incomplete understanding of the necessary effector cells and mechanisms that yield efficient tumor clearance.

The Effect of Osteoporosis Treatments on Fatigue Properties of Cortical Bone Tissue.

Bisphosphonates are commonly prescribed for treatment of osteoporosis. Long-term use of bisphosphonates has been correlated to atypical femoral fractures (AFF). AFFs arise from fatigue damage to bone tissue that cannot be repaired due to pharmacologic treatments.

Victory and defeat in the induction of a therapeutic response through vaccine therapy for human and canine brain tumors: a review of the state of the art.

Anti-tumor immunotherapy using tumor lysate-based vaccines has made great advances over recent decades. Cancer vaccines aim to elicit adaptive immune responses through various pathways by providing tumor and tumor-associated antigens with an immune stimulant or adjuvant. These anti-tumor vaccines are therefore developed as personalized treatments.

CD8+ T cell-independent tumor regression induced by Fc-OX40L and therapeutic vaccination in a mouse model of glioma.

Despite the growing number of preclinical and clinical trials focused on immunotherapy for the treatment of malignant gliomas, the prognosis for this disease remains grim. Although some promising advances have been made, the immune response stimulated as a result of immunotherapeutic protocols has been inefficient at complete tumor elimination, primarily due to our lack of understanding of the necessary effector functions of the immune system. We previously demonstrated that a tumor lysate vaccine/Fc-OX40L therapy is capable of inducing enhanced survival and tumor elimination in the GL261 mouse glioma model.

Canine intracranial gliomas: relationship between magnetic resonance imaging criteria and tumor type and grade.

Limited information is available to assist in the ante-mortem prediction of tumor type and grade for dogs with primary brain tumors. The objective of the current study was to identify magnetic resonance imaging (MRI) criteria related to the histopathological type and grade of gliomas in dogs. A convenience sample utilizing client-owned dogs (n=31) with gliomas was used.

Vaccination for invasive canine meningioma induces in situ production of antibodies capable of antibody-dependent cell-mediated cytotoxicity.

Malignant and atypical meningiomas are resistant to standard therapies and associated with poor prognosis. Despite progress in the treatment of other tumors with therapeutic vaccines, this approach has not been tested preclinically or clinically in these tumors. Spontaneous canine meningioma is a clinically meaningful but underutilized model for preclinical testing of novel strategies for aggressive human meningioma.

Clinical application of recombinant human bone morphogenetic protein in cats and dogs: a review of 13 cases.

Databases (2001-2008) for cases in which recombinant bone morphogenetic protein (rhBMP) was used to aid in management of orthopedic disease were reviewed and cases were categorized as non-unions, delayed unions, and cases expected to heal with difficulty. If follow-up in the medical record was < 6 mo for live animals, owners were surveyed by telephone. Thirteen cases (11 dogs, 2 cats) were identified; OP-1 (rhBMP-7) was used in 3 cases and INFUSE (rhBMP-2) in 10.