A5053538788- Vanadium and Halogenation Chemistry
- Virus-based gene therapy research
- Metal complexes synthesis and properties
- Heme Oxygenase-1 and Carbon Monoxide
- interferon and immune responses
- Viral Infectious Diseases and Gene Expression in Insects
- CAR-T cell therapy research
- Herpesvirus Infections and Treatments
- Adenosine and Purinergic Signaling
- Cytomegalovirus and herpesvirus research
- Polyomavirus and related diseases
- Ubiquitin and proteasome pathways
- Full-Duplex Wireless Communications
- RNA regulation and disease
- Biochemical and Molecular Research
- RNA modifications and cancer
- Fluoride Effects and Removal
- Plant Virus Research Studies
Ottawa Hospital
2017-2024
Ottawa Hospital Research Institute
2017-2024
University of Ottawa
2017-2023
Oncolytic viruses (OV) are an emerging class of anticancer bio-therapeutics that induce antitumor immunity through selective replication in tumor cells. However, the efficacy OVs as single agents remains limited. We introduce a strategy boosts therapeutic by combining their activity with immuno-modulating, small molecule protein tyrosine phosphatase inhibitors. report vanadium-based inhibitors enhance OV infection vitro and ex vivo, resistant cell lines. Furthermore, vanadium compounds...
Resistance to oncolytic virotherapy is frequently associated with failure of tumor cells get infected by the virus. Dimethyl fumarate (DMF), a common treatment for psoriasis and multiple sclerosis, also has anticancer properties. We show that DMF various fumaric maleic acid esters (FMAEs) enhance viral infection cancer cell lines as well human biopsies several viruses (OVs), improving therapeutic outcomes in resistant syngeneic xenograft models. This results durable responses, even models...
The poor prognosis of patients with advanced bone and soft-tissue sarcoma has not changed in the past several decades, highlighting necessity for new therapeutic approaches. Immunotherapies, including oncolytic viral (OV) therapy, have shown great promise a number clinical trials variety tumor types. However, effective application OV treating still remains to be demonstrated. Although few pre-clinical studies using distinct OVs been performed demonstrated benefit models, side-by-side...
The clinical efficacy of VSVΔ51 oncolytic virotherapy has been limited by tumor resistance to viral infection, so strategies transiently repress antiviral defenses are warranted. Pevonedistat is a first-in-class NEDD8-activating enzyme (NAE) inhibitor currently being tested in trials for its antitumor potential. In this study, we demonstrate that pevonedistat sensitizes human and murine cancer cells increase cell death, improve therapeutic outcomes resistant syngeneic models. Increased...
Abstract We have demonstrated that microtubule destabilizing agents (MDAs) can sensitize tumors to oncolytic vesicular stomatitis virus (VSVΔ51) in various preclinical models of cancer. The clinically approved T-DM1 (Kadcyla®) is an antibody-drug conjugate consisting HER2-targeting trastuzumab linked the potent MDA and maytansine derivative DM1. reveal combining with VSVΔ51 leads increased viral spread tumor killing trastuzumab-binding, VSVΔ51-resistant cancer cells. In vivo, co-treatment...
Oncolytic virotherapy is a clinically validated approach to treat cancers such as melanoma; however, tumor resistance virus makes its efficacy variable. Compounds sodium orthovanadate (vanadate) can overcome viral and synergize with RNA-based oncolytic viruses. In this study, we explored the basis of vanadate mode action identified key cellular components in vanadate's virus-enhancing mechanism using high-throughput kinase inhibitor screen. We found that several inhibitors affecting...
Strategies in genetic and pharmacological modulation of innate immunity to enhance oncolytic virotherapy (OV) efficacy are being explored. We have recently characterized the ability for vanadium-based compounds, a class pan-phosphatase (PP) inhibitors, potentiate OVs. next sought identify PPs that could be targeted OVs, akin vanadium. By conducting high-throughput screen library silencing RNA (siRNA) targeting human PPs, we uncovered several robustly enhanced infectivity oncolysis vesicular...
The Skin Investigation Network of Canada (SkIN Canada) completed a national Priority Setting Initiative to identify the top 10 knowledge uncertainties for Merkel cell carcinoma based on James Lind Alliance principles. Overall, 48 patients, clinicians and researchers provided input in two survey rounds one workshop. list research priorities will help skin community, funders policymakers address key benefit patients with carcinoma.
Abstract Oncolytic viruses (OVs) have emerged as promising anticancer treatment platforms, able to specifically replicate in and kill cancer cells. OVs also immunostimulatory effects, promoting antitumor immune responses, several strategies been developed combination with stimulate cancer-specific responses. Viral sensitizers (VSes) are molecules that alter the tumor antiviral response order improve efficacy of OVs. Such compounds can OV spread, transgene expression, promote long-term...