A5078928769- Virus-based gene therapy research
- interferon and immune responses
- CAR-T cell therapy research
- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- Cutaneous Melanoma Detection and Management
- Oral and Maxillofacial Pathology
- RNA Interference and Gene Delivery
- Cancer Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Cancer Immunotherapy and Biomarkers
- Tumors and Oncological Cases
- Lung Cancer Research Studies
- Vascular Malformations and Hemangiomas
- Animal Virus Infections Studies
- Ubiquitin and proteasome pathways
- RNA regulation and disease
- Cell Image Analysis Techniques
- Collagen: Extraction and Characterization
- Adenosine and Purinergic Signaling
- Muscle Physiology and Disorders
- AI in cancer detection
- Connective tissue disorders research
- Cellular Mechanics and Interactions
University of Ottawa
2021-2024
Ottawa Hospital
2020-2024
Ottawa Hospital Research Institute
2020-2024
Western University
2019
Lawson Health Research Institute
2017
Abstract Macrophage (Mϕ)-fibroblast interactions coordinate tissue repair after injury whereas miscommunications can result in pathological healing and fibrosis. We show that contracting fibroblasts generate deformation fields fibrillar collagen matrix provide far-reaching physical cues for Mϕ. Within created by or actuated microneedles, Mϕ migrate towards the force source from several hundreds of micrometers away. The presence a dynamic is critical to initiate direct migration. In contrast,...
Abstract The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier clinical effectiveness, as resistance this treatment can occur through the inhibition viral spread within tumor, potentially leading failures. Here we show that 4-octyl itaconate (4-OI), chemical derivative Krebs cycle-derived metabolite itaconate, enhances with VSVΔ51 various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids...
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...
Oncolytic virotherapy, using viruses such as vesicular stomatitis virus (VSVΔ51) and Herpes Simplex Virus-1 (HSV-1) to selectively attack cancer cells, faces challenges cellular resistance mediated by the interferon (IFN) response. Dimethyl fumarate (DMF) is used in treatment of multiple sclerosis psoriasis recognized for its anti-cancer properties has been shown enhance both VSVΔ51 HSV-1 oncolytic activity. Tepilamide (TPF) a DMF analog currently undergoing clinical trials...
Introduction Aberrant expression of anaplastic lymphoma kinase (ALK) is found in 3%–7% patients with non-small cell lung cancer (NSCLC). Alectinib a tyrosine inhibitor used as first-line treatment targeting ALK-positive tumors. We herein report two cases appendicitis highlighting it rare, possible adverse event alectinib. Case presentation The first case 60-year-old woman previous history stage 1 lobular breast and early-stage treated segmentectomy, subsequently presenting advanced NSCLC....
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...
Vascular endothelial growth factor (VEGF) and other pro-angiogenic factors have been investigated to enhance muscle tissue perfusion repair in Duchenne muscular dystrophy (DMD). Current understanding is limited by a lack of functional data following vivo delivery these factors. We previously used dynamic contrast-enhanced computed tomography monitor disease progression murine models DMD, but no study date has utilized this imaging technique assess vascular therapy preclinical model DMD. In...
Background Cancer of unknown primary (CUP) describes patients with metastatic disease without an identified tumor site. Successful diagnosis and treatment these remains difficult. Published guidelines on CUP have highlighted “favorable” subtype groups. We investigated a series to review adherence guidelines, identification cancers or subtypes. Methods Patients histologically confirmed at academic institution from 2012 2018 were identified. Patient demographics, presentation, diagnostic...
Abstract Background How well imaging size agrees with pathologic of gastric gastrointestinal stromal tumors (GISTs) is unknown. GIST risk stratification based on size, location, and mitotic rate. To inform decision making, the discrepancy between pathology for GISTs was investigated. Methods Imaging reports were reviewed 113 patients. Bland–Altman analyses intraclass correlation (ICC) assessed agreement pathology. Changes in clinical category due to identified. Results Computed tomography...
Immunotherapy and specifically oncolytic virotherapy has emerged as a promising option for cancer patients, with herpes simplex virus-1 (oHSV-1) expressing granulocyte macrophage colony stimulating factor being the first OV to be approved by FDA treatment of melanoma. However, not all cancers are sensitive responsive viruses (OVs). Our group demonstrated that fumaric maleic acid esters (FMAEs) very effective in sensitizing cells infection. Of note, these FMAEs include dimethyl fumarate (DMF,...
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...
Guidelines for the management of patients with cancer unknown primary (CUP), who have metastatic disease without an identified tumor site, evolved. We sought to describe diagnostic work-up and outcomes CUP in Canada over last decade. also identify factors associated improved prognosis CUP, including site identification, identification "favorable subtypes," concordance published guidelines.
<title>Abstract</title> Altered metabolism and defective innate immune responses are hallmarks of tumor cells, creating a niche that can be exploited by viruses with oncolytic properties. However, heterogeneity in to virotherapy is barrier clinical effectiveness. Resistance exists occurs via inhibition viral spread within the may result treatment failures. Here we show Krebs cycle-derived metabolite itaconate its chemical derivatives or natural isomers enhance VSVΔ51M various models...
Epidermal growth factor receptor (EGFR) mutations are usually oncogenic drivers of lung tumor development and progression. While common sensitizing respond well to targeted therapy, the relevance germline EGFR is less clear. We describe a 65-year-old, previously healthy, male diagnosed with non-small-cell cancer. Familial history for cancer negative. Targeted next-generation sequencing on biopsy sample revealed an atypical K757N mutation at 50% allele frequency genetic review acquired...