A5008948746- Chronic Lymphocytic Leukemia Research
- Autophagy in Disease and Therapy
- Cell death mechanisms and regulation
- Lymphoma Diagnosis and Treatment
- Calcium signaling and nucleotide metabolism
- Cancer-related Molecular Pathways
- Biochemical and Molecular Research
- Immunodeficiency and Autoimmune Disorders
- Acute Lymphoblastic Leukemia research
- Advanced Breast Cancer Therapies
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- NF-κB Signaling Pathways
- interferon and immune responses
- Chronic Myeloid Leukemia Treatments
- Sphingolipid Metabolism and Signaling
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Acute Myeloid Leukemia Research
- T-cell and B-cell Immunology
- Retinoids in leukemia and cellular processes
- Monoclonal and Polyclonal Antibodies Research
University of Alberta
2006-2025
Alberta Health Services
2025
University of Calgary
2024
University of Manitoba
2015-2024
UC Irvine Health
2023-2024
University of California, Irvine
2023-2024
Lancashire Teaching Hospitals NHS Foundation Trust
2024
CancerCare Manitoba
2014-2023
Research Institute in Oncology and Hematology
2015-2023
Children's Hospital Research Institute of Manitoba
2020
Ferroptosis is an iron-dependent, oxidative cell death, and distinct from apoptosis, necrosis autophagy. In this study, we demonstrated that lysosome disrupting agent, siramesine a tyrosine kinase inhibitor, lapatinib synergistically induced death reactive oxygen species (ROS) in MDA MB 231, MCF-7, ZR-75 SKBr3 breast cancer cells over 24 h time course. Furthermore, the iron chelator deferoxamine (DFO) significantly reduced cytosolic ROS following treatment with lapatinib. determined FeCl3...
Autophagy is a self-digestion process important for cell survival during starvation. It has also been described as form of programmed death. Mitochondria are regulators autophagy-induced death and damaged mitochondria often degraded by autophagosomes. Inhibition the mitochondrial electron transport chain (mETC) induces through generating reactive oxygen species (ROS). The role mETC inhibitors in unknown. Herein, we determined that complex I (rotenone) II (TTFA) induce autophagy transformed...
Caspases are activated during apoptosis and cleave specific proteins, resulting in the irreversible commitment to cell death. The signal transduction proteins MEKK1, p21-activated kinase 2, focal adhesion caspase substrates that contribute death response when cleaved. Thirty additional signaling were screened for their ability be cleaved apoptosis. Twenty-two of these not affected Jurkat cells stimulated undergo by Fas ligation, exposure ultraviolet-C or incubation with etoposide. Ras...
AbstractHypoxia (lack of oxygen) is a physiological stress often associated with solid tumors. Hypoxia correlates poor prognosis since hypoxic regions within tumors are considered apoptosis-resistant. Autophagy (cellular "self digestion") has been hypoxia during cardiac ischemia and metabolic as survival mechanism. However, although autophagy best characterized response, it can also function mechanism programmed cell death. Our results show that autophagic death induced by in cancer cells...
Summary Introduction A basal level of mitophagy is essential in mitochondrial quality control physiological conditions, while excessive contributes to cell death a number diseases including ischemic stroke. Signals regulating this process remain unknown. BNIP 3, pro‐apoptotic BH 3‐only protein, has been implicated as regulator mitophagy. Aims Both vivo and vitro models stroke, well 3 wild‐type knock out mice were used study. Results We show that its homologue 3L ( NIX ) are highly expressed...
Ferroptosis is a cell death pathway characterized by iron-dependent accumulation of reactive oxygen species (ROS) within the cell. The combination siramesine, lysosome disruptor, and lapatinib, dual tyrosine kinase inhibitor, has been shown to synergistically induce in breast cancer cells mediated ferroptosis. These treatments also autophagy but its role this synergistic unclear. In study, we determined that siramesine lapatinib initially induced ferroptosis changes an after 24 hours....
Chemotherapeutic genotoxins induce apoptosis in epithelial-cell-derived cancer cells. The death receptor ligand TRAIL also induces cells but generally fails to nontransformed We show here that the treatment of four different epithelial cell lines with topoisomerase II inhibitor etoposide combination (tumor necrosis factor [TNF]-related apoptosis-inducing ligand) a synergistic apoptotic response. mechanism effect results from etoposide-mediated increase expression receptors 4 (DR4) and 5...
Chemotherapeutic drugs that damage DNA kill tumor cells, in part, by inducing the expression of a death receptor such as Fas or its ligand, FasL. Here, we demonstrate epidermal growth factor (EGF) stimulation T47D breast adenocarcinoma and embryonic kidney epithelial (HEK293) cells protects these from Fas-induced apoptosis. EGF also inhibited caspase activation proteolysis signaling proteins downstream receptor, Cbl Akt/protein kinase B (Akt). Akt activity blocked Expression activated MCF-7...
T lymphocytes require two signals to be activated. The antigen-specific T-cell receptor can deliver the first signal, while ligation of surface molecule CD28 by antibodies or its cognate ligands B7-1 (CD80) B7-2 has been demonstrated sufficient for delivery second signal. Signaling via and results (i) in their costimulation cells produce numerous lymphokines including interleukin 2 (ii) prevention anergy induction. Little is known about pathway which mediates except that protein-tyrosine...
Abstract Brevinin‐2R is a novel non‐hemolytic defensin that was isolated from the skin of frog Rana ridibunda . It exhibits preferential cytotoxicity towards malignant cells, including Jurkat (T‐cell leukemia), BJAB (B‐cell lymphoma), HT29/219, SW742 (colon carcinomas), L929 (fibrosarcoma), MCF‐7 (breast adenocarcinoma), A549 (lung carcinoma), as compared to primary cells peripheral blood mononuclear (PBMC), T and human lung fibroblasts. overexpressing Bcl2, over‐expressing dominant‐negative...
Purpose Lenalidomide is an oral immunomodulatory drug with multiple effects on the immune system and tumor cell microenvironment leading to inhibition of malignant growth. Based encouraging reports lenalidomide in relapsed refractory chronic lymphocytic leukemia (CLL), we investigated first-line use single-agent CLL. Patients Methods Using a starting dose 10 mg/d for 21 days 28-day cycle weekly 5-mg escalations target 25 mg, encountered severe toxicities (tumor lysis, fatal sepsis) first two...