Integrated analysis of canine soft tissue sarcomas identifies recurrent mutations in TP53, KMT genes and PDGFB fusions.

Soft tissue sarcomas (STS) are a heterogenous group of mesenchymal tumors representing over 50 distinct types with overlapping histological features and non-specific anatomical locations. Currently, localized sarcomas are treated with surgery + / -  radiation in both humans and dogs with few molecularly targeted therapeutic options. However, to improve precision-based cancer therapy through trials in pet dogs with naturally occurring STS tumors, knowledge of genomic profiling and molecular drivers in both species is essential.

Integrated analysis of canine soft tissue sarcomas identifies recurrent mutations in genes and fusions.

Canine soft tissue sarcomas (STS) are a heterogenous group of malignant tumors arising from mesenchymal cells of soft tissues. This simplified collective of tumors most commonly arise from subcutaneous tissues, are treated similar clinically, and conventionally exclude other sarcomas with more definitive anatomical, histological, or biological features. Histologically, canine STS sub-types are difficult to discern at the light microscopic level due to their overlapping features.

Multi-modality imaging and therapeutics used in a case of canine spinal nephroblastoma.

A 4-year-old castrated male golden retriever dog was brought to a veterinary teaching hospital for evaluation of acute progressive paraparesis. Neurological examination indicated a spinal cord lesion between the third thoracic vertebra and third lumbar vertebrae. Magnetic resonance imaging (MRI) revealed an intradural, extra medullary, and/or intramedullary mass centered over the eleventh and twelfth thoracic disc space.

Clinical validation of a next-generation sequencing-based multi-cancer early detection "liquid biopsy" blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study.

Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here.

Intensity of perioperative analgesia but not pre-treatment pain is predictive of survival in dogs undergoing amputation plus chemotherapy for extremity osteosarcoma.

The purpose of this bi-institutional retrospective study was to determine whether, in dogs treated with limb amputation and adjunctive chemotherapy for osteosarcoma, oncologic outcomes are impacted by either: (1) baseline cancer pain severity, or (2) the approaches used for perioperative pain management. Data were extracted from the medical records of 284 dogs that underwent both limb amputation and chemotherapy (carboplatin and/or doxorubicin) between 1997 and 2017 for localized (non-metastatic) osteosarcoma of the appendicular skeleton. Kaplan-Meier survival curves and Cox proportional hazard (PH) models were used to determine the impact that retrospectively scored baseline pain levels (high vs.

Outcome of stereotactic body radiation for treatment of nasal and nasopharyngeal lymphoma in 32 cats.

Background: The safety and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of localized nasal lymphoma in cats has not been described.

Hypothesis: Stereotactic body radiation therapy with or without adjuvant chemotherapy is an effective and well-tolerated treatment for localized nasal lymphoma in cats.

Animals: Thirty-two client owned cats referred to Colorado State University for the treatment of nasal lymphoma.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

An aggressive CD4 CD8 T-cell neoplasm in young English bulldogs.

T-cell leukemia/lymphoma accounts for roughly 30% of all types of lymphoproliferative neoplasia in dogs. Two forms of T-cell lymphoma (T-zone and peripheral T-cell lymphoma) exhibit breed-specific predilections. During the course of routine immunophenotyping, we observed a breed-specific presentation of a unique form of T-cell leukaemia in young English bulldogs.

Immune pathways and TP53 missense mutations are associated with longer survival in canine osteosarcoma.

Osteosarcoma affects about 2.8% of dogs with cancer, with a one-year survival rate of approximately 45%. The purpose of this study was to characterize mutation and expression profiles of osteosarcoma and its association with outcome in dogs.

Characterizing the molecular and immune landscape of canine bladder cancer.

Transitional cell carcinoma (TCC), also known as urothelial carcinoma, is the most common bladder cancer in humans and dogs. Approximately one-quarter of human TCCs are muscle-invasive and associated with a high risk of death from metastasis. Canine TCC (cTCC) tumours are typically high-grade and muscle-invasive.

Multi-omics approach identifies germline regulatory variants associated with hematopoietic malignancies in retriever dog breeds.

Histiocytic sarcoma is an aggressive hematopoietic malignancy of mature tissue histiocytes with a poorly understood etiology in humans. A histologically and clinically similar counterpart affects flat-coated retrievers (FCRs) at unusually high frequency, with 20% developing the lethal disease. The similar clinical presentation combined with the closed population structure of dogs, leading to high genetic homogeneity, makes dogs an excellent model for genetic studies of cancer susceptibility.

Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs.

Purpose: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression.

Prospective evaluation of flow cytometric characteristics, histopathologic diagnosis and clinical outcome in dogs with naïve B-cell lymphoma treated with a 19-week CHOP protocol.

Canine B-cell lymphoma is a clinically heterogenous disease; however, it is generally treated as a single disease entity. The purpose of this clinical trial was to prospectively evaluate naïve canine B-cell lymphoma patients using histopathology, flow cytometry (FC) and a standardized chemotherapy protocol to better define subsets of this disease that may respond differently to treatment. Sixty-four dogs with naïve multicentric B-cell lymphoma were treated with a standardized 19-week CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy protocol.

Canine osteosarcoma genome sequencing identifies recurrent mutations in and the histone methyltransferase gene .

Osteosarcoma (OS) is a rare, metastatic, human adolescent cancer that also occurs in pet dogs. To define the genomic underpinnings of canine OS, we performed multi-platform analysis of OS tumors from 59 dogs, including whole genome sequencing ( = 24) and whole exome sequencing (WES;  = 13) of primary tumors and matched normal tissue, WES ( = 10) of matched primary/metastatic/normal samples and RNA sequencing ( = 54) of primary tumors. We found that canine OS recapitulates features of human OS including low point mutation burden (median 1.

Colorado State University, Pet Hospice Program.

Serving clients since 2004, Colorado State University's Veterinary Teaching Hospital is the first and only program to offer a student-run pet hospice program. Under the supervision of faculty and staff advisors, student volunteers provide home hospice care to families who have a terminally ill pet. This article describes the history of the program, how it is organized, the roles and responsibilities of the students, the challenges of the program and future goals.

Proliferative and Invasive Colorectal Tumors in Pet Dogs Provide Unique Insights into Human Colorectal Cancer.

Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colorectal tumors from 20 canine cases, and evaluated their molecular homology to human colorectal cancer (CRC). First, proliferative canine tumors harbor overactivated WNT/β-catenin pathways and recurrent CTNNB1 (β-catenin) mutations S45F/P, D32Y and G34E.

Pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide in cats after oral, intravenous, and intraperitoneal administration of cyclophosphamide.

OBJECTIVE To characterize pharmacokinetics of cyclophosphamide and 4-hydoxycyclophosphamide (4-OHCP) in the plasma of healthy cats after oral, IV, and IP administration of cyclophosphamide. ANIMALS 6 healthy adult cats. PROCEDURES Cats were randomly assigned to receive cyclophosphamide (200 mg/m) via each of 3 routes of administration (oral, IV, and IP); there was a 30-day washout period between successive treatments.

A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model.

Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy.

Defining the Pharmacodynamic Profile and Therapeutic Index of NHS-IL12 Immunocytokine in Dogs with Malignant Melanoma.

Background: Interleukin (IL)-12 is a pro-inflammatory cytokine that mediates T-helper type 1 responses and cytotoxic T-cell activation, contributing to its utility as anti-cancer agent. Systemic administration of IL-12 often results in unacceptable toxicity; therefore, strategies to direct delivery of IL-12 to tumors are under investigation. The objective of this study was to assist the preclinical development of NHS-IL12, an immunocytokine consisting of an antibody, which targets necrotic tumor regions, linked to IL-12.

Outcome and prognostic factors for osteosarcoma of the maxilla, mandible, or calvarium in dogs: 183 cases (1986-2012).

Objective: To describe the biological behavior, clinical outcome, and prognostic factors of osteosarcoma of the maxilla, mandible, or calvarium in dogs.

Design: Retrospective case series.

Animals: 183 client-owned dogs with osteosarcoma of the maxilla, mandible, or calvarium.

Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.

Background: Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options.

Disease distribution in canine patients with acanthocytosis: 123 cases.

Background: An acanthocyte is an abnormally shaped erythrocyte. In veterinary medicine, acanthocytes have historically been associated with canine hemangiosarcoma. In human medicine, acanthocytes are rarely observed with neoplastic disease and are more commonly associated with a variety of hereditary and acquired diseases.