A5030344406- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Radiopharmaceutical Chemistry and Applications
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Protein Degradation and Inhibitors
- Cardiac tumors and thrombi
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Angiogenesis and VEGF in Cancer
- Click Chemistry and Applications
- Ubiquitin and proteasome pathways
- Neuroblastoma Research and Treatments
- Medical Imaging Techniques and Applications
- Histone Deacetylase Inhibitors Research
Terry Fox Research Institute
2023-2024
Provincial Health Services Authority
2019
Article31 October 2019Open Access Source DataTransparent process Class I HDAC inhibitors enhance YB-1 acetylation and oxidative stress to block sarcoma metastasis Amal M El-Naggar orcid.org/0000-0002-3202-6171 Department of Pathology & Laboratory Medicine, University British Columbia, Vancouver, BC, Canada Molecular Oncology, BC Cancer, part the Provincial Health Services Authority, Pathology, Faculty Menoufia University, Shibin El Kom, Egypt Search for more papers by this author Syam...
Most HER2-positive metastatic breast cancer patients continue to relapse. Incomplete access all target cells in metastases and tumor tissues is a potential mechanism of resistance trastuzumab. The location locally bound trastuzumab was evaluated vivo as xenografts or models mice. Microenvironmental elements tumors were related using immunohistochemical staining include tight junctions, vasculature, vascular maturity, vessel patency, hypoxia HER2 look for correlations. Trastuzumab alone...
Abstract Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a stress-responsive hub that inhibits the translation eEF2, and consequently mRNA elongation, in response to hypoxia nutrient deprivation. EEF2K also involved DNA damage but its role crosslinks, as induced by cisplatin, not known. Here we found eEF2K critical mediate cellular cisplatin. We uncovered deficient cells are more resistant cisplatin treatment. Mechanistically, deficiency blunts activation of associated ATM ATR...
Tumour hypoxia presents a barrier to conventional chemotherapy and radiation therapy. To combat hypoxic cells number of modifying treatments are currently in development. In this study we assessed the potential for inhibiting DNA double strand break repair by targeting DNA-dependent protein kinase (DNA-PK) report synthesis vitro efficacy BCCA621C (1), activated inhibitor DNA-PK. We found that DNA-PK deficient radiosensitive compared proficient effect can be observed using both small molecule...
Many cancer research efforts focus on exploiting genetic-level features that may be targeted for therapy. Tissue-level of the tumour microenvironment also represent useful therapeutic targets. Here we investigate presence low oxygen tension and sensitivity to NOS inhibition vasculature as potential tumour-specific by hypoxic cytotoxins, a class therapeutics currently under investigation. We have previously demonstrated tirapazamine (TPZ) mediates central vascular dysfunction in tumours. TPZ...
ABSTRACT Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a stress-responsive hub that inhibits the translation eEF2, and consequently mRNA elongation, in response to hypoxia nutrient deprivation. EEF2K also involved DNA damage but its role crosslinks, as induced by cisplatin, not known. Here we found eEF2K critical mediate cellular cisplatin. We uncovered deficient cells are more resistant cisplatin treatment. Mechanistically, deficiency blunts activation of associated ATM ATR...
Abstract We have previously shown that trastuzumab distributes heterogeneously within MDA-435-Her2 xenografts. Though peak accumulation occurs 24h after administration & was detected greater than 150 µm from many vessels, there remained substantial Her2+ve areas were negative for bound drug. Methods: human carcinoma xenografts grown in NOD/SCID mice as solid tumors or metastatic models following ip iv injection. Tumors MR-imaged (T1-weighted) with a 500kDa Gd-labeled hyperbranched...
Abstract Despite significant success, the response of Her2+ patients to trastuzumab (TzMAb, Herceptin ®) is varied, with many still experiencing tumor progression. We have used 3D tissue, xenograft and metastatic models examine microregional distribution TzMAb when administered alone or in combination bevacizumab (BvMAb). Methods: Her2 positive (Her2+) SKOV-3 ovarian MDA361, JIMT-1, BT474 mammary cancer cells were grown as tissue discs, spheroids xenografts. expression was ranked SKOV3...
The MYC oncogenes contribute to more than 50% of all human cancers, but their therapeutic targeting has proven challenging. MYC/MYCN amplification in childhood medulloblastoma (MB) and neuroblastoma (NB) determine aggressive disease high mortality, underlying the need for novel effective therapies. MYC-driven transformation is energy demanding impairs cell survival under nutrient deprivation (ND), a characteristic stress condition within tumor microenvironment. We recently identified...