Anthony Mutsaers

Anthony Mutsaers
University of Guelph | UOGuelph · Department of Clinical Studies

DVM, PhD, DACVIM Oncology

About

77
Publications
13,338
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2,121
Citations
Citations since 2016
49 Research Items
1112 Citations
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150

Publications

Publications (77)
Article
Full-text available
Urokinase plasminogen activator (uPA) and its receptor uPAR promote cancer invasion and metastasis and are emerging therapeutic targets in both human and canine malignancies. While their clinical significance is well-characterized in multiple human tumor types, studies investigating their roles in osteosarcoma are lacking. The objectives of this st...
Article
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are primary myeloid neoplasms in dogs generally considered to have a poor outcome. In this study we assessed toxicity, efficacy and outcome of concurrent administration of doxorubicin and cytarabine in 11 dogs with myeloid neoplasia. Bone marrow specimens were reviewed by three patholo...
Article
Full-text available
In collaboration with the American College of Veterinary Pathologists.
Article
Rapamycin has been reported to reduce cancer cell survival in certain tumors following radiation therapy, but the mechanisms driving this phenomenon are unclear. Rapamycin inhibits mTOR signaling, a pathway responsible for several essential cell functions. The objective of this study was to investigate the effects of rapamycin and radiation on the...
Article
Full-text available
Survivin is a member of the inhibitor of apoptosis family of proteins and has been reported to be highly expressed in a variety of cancer types, making it a high priority target for cancer vaccination. We previously described a heterologous prime-boost strategy using a replication-deficient adenovirus, followed by an oncolytic rhabdovirus that gene...
Article
Full-text available
Background Malignant melanoma in dogs is considered to be largely resistant to conventional chemotherapy, although responses to carboplatin have been documented. Invasion and early metastasis are common features of certain melanoma subtypes that contribute to tumour progression despite aggressive local and systemic therapy. Upregulation of the PI3K...
Article
Urothelial carcinoma (UC) is the most common urinary tumor in dogs and despite combinational therapies, only modest improvements in survival have been achieved in recent years. Given the utility of monoclonal antibodies against PD-1 and PD-L1 in human UC, we evaluated the protein and mRNA expression in three established canine urothelial carcinoma...
Article
Full-text available
Urothelial carcinoma (UC) is the most common urinary tumour in dogs. Despite a range of treatment options, prognosis remains poor in dogs. In people, breakthroughs with checkpoint inhibitors have established new standards of care for muscle-invasive bladder cancer patients and elevated levels of PD-1 suggest immune checkpoint blockade may be a nove...
Article
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Background Canine urothelial carcinoma is the most common form of canine bladder cancer. Treatment with chemotherapy has variable response rates leading to most dogs succumbing to their disease within a year. Cannabidiol is an emerging treatment within the field of oncology. In reported in vivo studies, cannabidiol has induced apoptosis, reduced ce...
Conference Paper
Introduction Human pediatric and canine osteosarcoma (OSA) are both highly metastatic primary bone cancers that share molecular and clinical similarities. Urokinase plasminogen activator (uPA) and its receptor uPAR promote invasion, metastasis and angiogenesis in multiple cancer types and have been shown to play critical roles in malignant characte...
Article
Full-text available
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 hi...
Article
The effects of radiation therapy may be potentiated by combining radiation therapy with secondary therapies. Clinically, radiation therapy has been combined with bisphosphonates for treatment of canine appendicular osteosarcoma for years. The objective of this study was to determine if the timing of administration of bisphosphonates in relation to...
Article
Full-text available
This survey aimed to investigate and compare diet type and supplement use between dogs (Canis lupus familiaris, L.) with cancer and a population of owner‐reported healthy dogs and to assess the sources of information dog owners consult. Respondents were mainly from English‐speaking countries. Dogs were considered healthy (N = 213) if owners reporte...
Article
Full-text available
Osteosarcoma (OSA) is an aggressive primary bone tumor in the domestic dog that most often occurs within the appendicular skeleton. Despite the use of adjuvant chemotherapy, most dogs succumb to metastatic disease within 1 year of diagnosis. To improve this outcome, substantial research is currently focused on investigating novel therapies. Herein,...
Article
Full-text available
Osteosarcoma (OSA) is the most common primary bone cancer in children, adolescents and dogs. Current combination surgical and chemotherapeutic treatments have increased survival. However, in recurrent or metastatic disease settings, the prognosis significantly decreases, representing an urgent need for better second‐line and novel chemotherapeutics...
Article
Full-text available
Lymphoma is the most common hematopoietic tumour in dogs and is remarkably similar to the human disease. Tumour biomarker discovery is providing new tools for diagnostics and predicting therapeutic response and clinical outcome. MicroRNAs are small non-coding RNAs that participate in post-transcriptional gene regulation and their aberrant expressio...
Article
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Purpose of Review Osteosarcoma (OS) is the most common cancer of bone, yet is classified as a rare cancer. Treatment and outcomes for OS have not substantively changed in several decades. While the decoding of the OS genome greatly advanced the understanding of the mutational landscape of OS, immediately actionable therapeutic targets were not appa...
Article
Osteosarcoma (OSA) is a malignant tumor of middle‐aged dogs and adolescent humans. The clinical outcome of OSA has not improved over more than three decades, and dogs typically succumb to metastatic disease within 6 months despite tumor resection through limb amputation and adjuvant chemotherapy. Therefore, undetectable tumor cells with potential t...
Article
Full-text available
Gold nanoparticles (AuNPs) are a focus of growing medical research applications due to their unique chemical, electrical and optical properties. Because of uncertain toxicity, “green” synthesis methods are emerging, using plant extracts to improve biological and environmental compatibility. Here we explore the biodistribution of green AuNPs in mice...
Article
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Background Osteosarcoma (OSA) is a common bone tumor of mesenchymal origin in dogs. Chemotherapy delays metastasis, yet most dogs die of this disease within 1 year of diagnosis. The high metabolic demand of cancer cells promotes proton pump upregulation, leading to acidification of the tumor microenvironment and chemoresistance. The potassium‐spari...
Article
Canine osteosarcoma is a devastating disease with an overall poor prognosis. Radiation therapy and bisphosphonates are currently used in combination for palliative treatment, despite a paucity of literature that investigates their combined use. The objectives of this study were to assess the in vitro effects of radiation therapy and bisphosphonates...
Article
Full-text available
Background Osteosarcoma (OSA) is the most common bone cancer in canines. Both transforming growth factor beta (TGFβ) and Hippo pathway mediators have important roles in bone development, stemness, and cancer progression. The role of Hippo signalling effectors TAZ and YAP has never been addressed in canine OSA. Further, the cooperative role of TGFβ...
Article
Full-text available
Dogs diagnosed with appendicular osteosarcoma typically succumb to metastatic disease within a year of diagnosis. The current standard of care for curative intent, amputation followed by adjuvant chemotherapy, increases survival time but chemoresistance is a major contributor to mortality. Unfortunately, the mechanisms driving the progression of me...
Data
Expression of autophagy related proteins in canine cells treated with the autophagy inhibitor spautin-1 and doxorubicin. Western blot expression of P62 and LC3 (microtubule‑associated protein light chain 3) in metastatic canine osteosarcoma cells treated with spautin-1 (Low = 15 μM, High = 120 μM) or doxorubicin (IC50) for 24 hours each as a single...
Data
Cell viability dose-response curves for canine cells exposed to the autophagy inhibitor spautin-1. Cell viability measured using a resazurin assay. The solid vertical line denotes the IC50 value, and the dashed vertical lines denote 95% confidence interval (CI) bounds. Error bars denote standard deviation (SD) [CV, coefficient of variation]. (TIFF)
Data
Canine cell line experimental details. (PDF)
Data
Cell viability dose-response curves for canine cells exposed to doxorubicin. Cell viability measured using a resazurin assay. The solid vertical line denotes the IC50 value, and the dashed vertical lines denote 95% confidence interval (CI) bounds. Error bars denote standard deviation (SD) [CV, coefficient of variation]. (TIFF)
Data
Colony formation dose-response curves for canine cells treated with doxorubicin. Surviving fraction measured using a colony formation assay. (TIFF)
Article
OBJECTIVE To determine the effectiveness of metronomic cyclophosphamide (MC) chemotherapy (primary treatment of interest) with adjuvant meloxicam administration as maintenance treatment for dogs with appendicular osteosarcoma following limb amputation and carboplatin chemotherapy. DESIGN Retrospective case series with nested cohort study. ANIMALS 3...
Article
Gold nanoparticles synthesized using plant extracts with medicinal properties have gained traction in recent years, especially for their use in various biomedical applications. Colloidal stability of these nanoparticles in different environments is critical to retain the expected therapeutic/diagnostic efficacy and toxicological outcome. Any change...
Article
Full-text available
For a vaccine to be effective it must induce a sufficiently robust and specific immune response. Multi-site injection protocols can increase the titers of rabies virus-neutralizing antibodies. Hypothetically, spreading a vaccine dose across multiple lymphatic drainage regions could also potentiate T cell responses. We used a replication-deficient a...
Article
OBJECTIVE To evaluate the effects of IV diphenhydramine hydrochloride administration on cardiorespiratory variables in anesthetized dogs undergoing mast cell tumor (MCT) excision. DESIGN Randomized, blinded clinical trial. ANIMALS 16 client-owned dogs with MCTs. PROCEDURES In a standardized isoflurane anesthesia session that included mechanical ven...
Article
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This retrospective study evaluated the outcomes of dogs with macroscopic pulmonary metastasis of appendicular osteosarcoma (OSA) treated with toceranib. Medical records of 20 dogs with macroscopic pulmonary metastasis of OSA that received toceranib were reviewed. The median dose and duration of toceranib administration were 2.52 mg/kg (range: 2.12...
Article
This retrospective study investigated the outcome of 33 dogs with splenic hemangiosarcoma treated with surgery followed by adjuvant dose-intensified doxorubicin (DOX) with or without low-dose metronomic cyclophosphamide (LDM-C) maintenance therapy. Among the 33 dogs, 18 dogs received LDM-C. Clinical stage was available for all dogs (5 stage I, 18 s...
Article
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Sterile hemorrhagic cystitis (SHC) is an important complication of cyclophosphamide chemotherapy in dogs as it is reported in up to 23% of cases with various protocols. The current study reports toxicities of a protocol of metronomic cyclophosphamide, and identifies risk factors for development of adverse effects. A retrospective cohort study of do...
Article
In humans, multiple cytokines have been linked to the development of lymphoma, and are relevant biomarkers for response to chemotherapy and prognosis. In contrast, only a few circulating cytokines have been studied in dogs with lymphoma. We prospectively enrolled thirty-one dogs newly diagnosed with multicentric lymphoma. Immunophenotype was determ...
Article
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Heat shock proteins (HSPs) are molecular chaperones subdivided into several families based on their molecular weight. Due to their cytoprotective roles, these proteins may help protect cancer cells against chemotherapy-induced cell death. Investigation into the biologic activity of HSPs in a variety of cancers including primary bone tumors, such as...
Chapter
We use the emerging concept of metronomic chemotherapy as an example of how clinical trials in human cancer patients and veterinary clinical trials in dogs with cancer can suggest strategies for improving the predictive power of preclinical models. The last decade has seen a number of clinical trials that have attempted to take metronomic chemother...
Article
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Background Radiation therapy is a palliative treatment modality for canine osteosarcoma, with transient improvement in analgesia observed in many cases. However there is room for improvement in outcome for these patients. It is possible that the addition of sensitizing agents may increase tumor response to radiation therapy and prolong quality of l...
Article
The objective of this study was to determine the pharmacokinetics of diphenhydramine (DPH) in healthy dogs following a single i.v. or i.m. dose. Dogs were randomly allocated in two treatment groups and received DPH at 1 mg/kg, i.v., or 2 mg/kg, i.m. Blood samples were collected serially over 24 h. Plasma concentrations of DPH were determined by hig...
Article
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Osteosarcoma is the most common form of primary bone tumors with high prevalence in children. Survival rates of osteosarcoma are low, especially in the case of metastases. Mouse models of this disease have been very valuable in investigation of mechanisms of tumorigenesis, metastasis, as well as testing possible therapeutic options. In this chapter...
Article
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Osteosarcoma (OS) is the most common cancer of bone occurring mostly in teenagers. Despite rapid advances in our knowledge of the genetics and cell biology of OS, significant improvements in patient survival have not been observed. The identification of effective therapeutics has been largely empirically based. The identification of new therapies a...
Article
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RECQL4 mutations are associated with Rothmund Thomson Syndrome (RTS), RAPADILINO Syndrome and Baller-Gerold Syndrome. These patients display a range of benign skeletal abnormalities such as low bone mass. In addition, RTS patients have a highly increased incidence of osteosarcoma (OS). The role of RECQL4 in normal adult bone development and homeost...
Article
Osteosarcoma is a disease with many complex genetic abnormalities but few well defined genetic drivers of tumor initiation and evolution. The disease is diagnosed and defined through the observation of malignant osteoblastic cells that produce osteoid, however the exact cell of origin for this cancer remains to be definitively defined. Evidence exi...
Article
Osteosarcoma is the most common primary cancer of bone and one that predominantly affects children and adolescents. Osteoblastic osteosarcoma represents the major subtype of this tumor, with approximately equal representation of fibroblastic and chondroblastic subtypes. We and others have previously described murine models of osteosarcoma based on...
Article
Full-text available
This retrospective study evaluated the ocular side effects of cancer-bearing dogs and cats treated with external-beam Cobalt-60 (Co-60) radiation in which one or both orbit(s) were included in the radiation field. A total of 37 dogs and 12 cats presented to the Ontario Veterinary College during the 10-year study period (1999-2009) were evaluated. T...
Article
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Osteosarcoma is the most common form of bone cancer. Pivotal insight into the genes involved in human osteosarcoma has been provided by the study of rare familial cancer predisposition syndromes. Three kindreds stand out as predisposing to the development of osteosarcoma: Li-Fraumeni syndrome, familial retinoblastoma and RecQ helicase disorders, wh...
Article
Thirteen dogs with histologically confirmed osteosarcoma were treated with surgery and adjuvant chemotherapy. None of the dogs had evidence of metastatic disease at the time of diagnosis. The chemotherapy protocol consisted of four cycles of doxorubicin (15mg/m(2)) and carboplatin (150-220mg/m(2)) intravenously every three weeks. Both cytotoxic age...
Article
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CT-322 is a new anti-angiogenic therapeutic agent based on an engineered variant of the tenth type III domain of human fibronectin, i.e., an Adnectin™, designed to inhibit vascular endothelial growth factor receptor (VEGFR)-2. This PE Gylated Adnectin was developed using an mRNA display technology. CT-322 bound human VEGFR-2 with high affinity (K(D...
Article
s: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 15-19, 2009; Boston, MA Low dose, metronomic chemotherapy with cyclophosphamide has shown activity in the treatment of advanced breast cancer, and has been paired with targeted agents such as trastuzumab and bevacizumab for long term therapy, with encouragin...
Article
Low dose metronomic (LDM) chemotherapy has shown promising activity in many preclinical as well as some phase II clinical studies involving various tumor types. It involves chronic but close, regular administration of chemotherapeutic drugs without prolonged breaks. Combination of LDM chemotherapy with targeted biologic agents such as antiangiogeni...
Article
Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, ha...
Article
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The objective of this study was to characterize treatment-induced circulating ligand changes during therapy with epidermal growth factor receptor (EGFR) inhibitors and evaluate their potential as surrogate indicators of the optimal biological dose. Conditioned medium from human tumor cell lines, ascites fluid from tumor xenografts, and plasma sampl...
Article
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Vascular endothelial growth factor (VEGF) is a potent proangiogenic protein that activates VEGF receptor (VEGFR) tyrosine kinases expressed by vascular endothelial cells. We previously showed that one of these receptors, VEGFR-2, has a truncated soluble form (sVEGFR-2) that can be detected in mouse and human plasma. Because activation of VEGFR-2 pl...
Article
Using chemotherapy drugs as antiangiogenic agents is a new use for drugs that have been around for a long time. The favorable toxicity profile and reduced cost make low-dose continuous "metronomic" chemotherapy trials appealing, but there is still much to be learned. Challenges ahead include determination of the optimal tumor types, drugs, doses, s...
Article
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Cancer patients treated with antiangiogenic multitargeted receptor tyrosine kinase (RTK) inhibitors show increased levels of plasma VEGF and placental growth factor and decreased levels of soluble VEGF receptor-2, thus implicating these overall changes as a possible class effect of such drugs and raising the possibility of their exploitation as sur...
Article
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Positive-contrast methods can augment negative-contrast methods for CMR evaluation of transplanted cell fate in vivo. This study correlated positive-contrast signal characteristics in the rabbit hind-limb with xenograft cell number (rat fibroblasts bearing endocytosed 1 microm Bang's particles) at different stages of Gd-DTPA administration and 1 mm...