A5030910035- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Cancer, Lipids, and Metabolism
- Hormonal and reproductive studies
- Extracellular vesicles in disease
- Glioma Diagnosis and Treatment
- Ginseng Biological Effects and Applications
- Cholesterol and Lipid Metabolism
- Radiopharmaceutical Chemistry and Applications
- Hormonal Regulation and Hypertension
- Natural product bioactivities and synthesis
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Pharmacological Effects of Natural Compounds
- Healthcare and Venom Research
- MicroRNA in disease regulation
- Growth Hormone and Insulin-like Growth Factors
- Steroid Chemistry and Biochemistry
- Leech Biology and Applications
- Antioxidant Activity and Oxidative Stress
- Vitamin D Research Studies
- Complementary and Alternative Medicine Studies
- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
Vancouver General Hospital
2012-2023
The University of Texas MD Anderson Cancer Center
2009-2023
General Department of Preventive Medicine
2023
BC Cancer Agency
2000-2022
The Prostate Centre
2012-2022
University of British Columbia
2010-2021
Vancouver Coastal Health
2015-2019
Vancouver Coastal Health Research Institute
2019
First Hospital of Jilin University
2013
Jilin University
2013
Although systemic androgen deprivation prolongs life in advanced prostate cancer, remissions are temporary because patients almost uniformly progress to a state of castration-resistant cancer (CRPC) as indicated by recurring PSA. This complex process progression does not seem be stochastic the timing and phenotype highly predictable, including observation that most androgen-regulated genes reactivated despite castrate levels serum androgens. Recent evidence indicates intraprostatic androgens...
Prostate cancer is the leading type of diagnosed in men. In 2010, ~217,730 new cases prostate were reported United States. Prompt diagnosis disease can substantially improve its clinical outcome. Improving capability for early detection, as well developing therapeutic targets advanced are research priorities that will ultimately lead to better patient survival. Eukaryotic cells secrete proteins via distinct regulated mechanisms which either ER/Golgi dependent or microvesicle mediated. The...
Abstract BACKGROUND Emerging evidence suggests that androgens and the androgen receptor (AR) are important mediators of castration‐resistant prostate cancer (CRPC) progression. Increased expression several enzymes responsible for cholesterol synthesis conversion into downstream has been documented in human CRPC tumors comparison to primary tumors. Based on these observations it is hypothesized its overall regulation within cell altered, thus modifying precursor levels de novo castrate...
Abstract Purpose: Clusterin is a cytoprotective chaperone protein that promotes cell survival and confers broad-spectrum treatment resistance. OGX-011 2′-methoxyethyl–modified phosphorothioate antisense oligonucleotide complementary to clusterin mRNA, has prolonged tissue half life, enhances drug efficacy in xenograft models, reduces expression humans with biologically effective dose of 640 mg. The objective this study was determine recommended phase II combination docetaxel. Experimental...
VT-464 is a novel, nonsteroidal, small-molecule CYP17A1 inhibitor with 17,20-lyase selectivity. This study evaluates the anticancer activity of compared abiraterone (ABI) in castrate-resistant prostate cancer cell lines and xenograft models that are enzalutamide (ENZ)-responsive (C4-2) or ENZ-resistant (MR49C, MR49F). In vitro, androgen receptor (AR) transactivation was assessed by probasin luciferase reporter, whereas AR AR-regulated genes steroidogenic pathway enzymes were Western blot...
The androgen receptor (AR) is one of the most studied drug targets for treatment prostate cancer. However, all current anti-androgens directly interact with AR at binding site, which prone to resistant mutations, calling new strategies inhibition. study represents first attempt use virtual screening identify inhibitors activation function-2 (AF2) human AR. By combining large-scale docking experimental approaches, we were able several small molecules that AF2 and effectively prevent...
// Elham Hosseini-Beheshti 1, 3 , Wendy Choi Louis-Bastien Weiswald 4 Geetanjali Kharmate Mazyar Ghaffari Mani Roshan-Moniri Mohamed D. Hassona Leslie Chan Mei Yieng Chin Isabella T. Tai Paul S. Rennie 2, Ladan Fazli Emma Tomlinson Guns 1 Department of Experimental Medicine University British Columbia, Vancouver, V6H 3Z6, Canada 2 Urologic Sciences The Vancouver Prostate Centre Division Gastroenterology, Correspondence to: Guns, e-mail: eguns@prostatecentre.com Keywords: exosomes, cancer...
Dimethyl sulfoxide (DMSO) is currently used as an alternative treatment for various inflammatory conditions well cancer. Despite its widespread use, there a paucity of data regarding safety and efficacy mechanism action in human cells. Herein, we demonstrate that DMSO has ex-vivo anti-inflammatory activity using Escherichia coli- (E. coli) herpes simplex virus-1 (HSV-1)-stimulated whole blood. Specifically, found between 0.5%-2%, significantly suppressed the expression many pro-inflammatory...
Exosomes proteins and microRNAs have gained much attention as diagnostic tools biomarker potential in various malignancies including prostate cancer (PCa). However, the role of exosomes membrane-associated receptors, particularly epidermal growth factor receptor (EGFR) mediators cell proliferation invasion PCa progression remains unexplored. EGFR is frequently overexpressed has been associated with aggressive forms PCa. While cells tissues express EGFR, it unknown whether derived from or...
The methanol extract of the underground part Rhodiola rosea was found to show inhibitory activity against Staphylococcus aureus. Bioactivity-guided fractionation a 95% ethanol from stems R. led isolation five compounds: gossypetin-7-O-l-rhamnopyranoside (1), rhodioflavonoside (2), gallic acid (3), trans-p-hydroxycinnamic (4) and p-tyrosol (5). Their structures were elucidated by UV, IR, MS NMR data, as well comparison with those literature. Compounds 1 2 evaluated for their antibacterial...
Bortezomib and the other proteasome inhibitors that are currently under clinical investigation bind to catalytic sites of proteasomes competitive inhibitors. We hypothesized act through a noncompetitive mechanism might overcome some forms bortezomib resistance.5-amino-8-hydroxyquinoline (5AHQ) was identified screen 27-compound chemical library based on quinoline pharmacophore identify Inhibition activity by 5AHQ tested measuring 7-amino-4-methylcoumarin (AMC) release from substrate...
Aberrant cholesterol metabolism is increasingly appreciated to be essential for prostate cancer initiation and progression. Transcript expression of the high-density lipoprotein-cholesterol receptor scavenger B1 (SR-B1) elevated in primary cancer. Hypothesizing that SR-B1 may help facilitate malignant transformation, we document increased protein transcript relative normal epithelium persists lethal castration-resistant (CRPC) metastasis. As intratumoral steroid synthesis from precursor can...
Abstract BACKGROUND De novo androgen synthesis and subsequent receptor (AR) activation has recently been shown to contribute castration‐resistant prostate cancer (CRPC) progression. Herein we provide evidence that fatty acids (FA) can trigger within steroid starved (CaP) tumor cells. METHODS Tumoral FA levels were assessed by GC–MS LC–MS, respectively. Profiles of genes proteins involved in steroidogenesis fluorescence microscopy, immunohistochemistry, microarray expression profiling Western...
Benign prostatic hyperplasia (BPH) affects many men after the age of 50 years. Inflammation and oxidative stress along with apoptotic changes are thought to play an important role in pathology BPH. Pomegranate contains a variety polyphenolic compounds that have been studied medley diseases for their anti-oxidant, anti-inflammatory pro-apoptotic properties. Therefore, this study examined effect Fruit Extract (PFE) on development BPH using testosterone-induced model rats.A total 48 rats were...
We explored the efficacy of ginsenoside Rh2 and examined its impact on effective dose paclitaxel mitoxantrone in LNCaP prostate tumor model.Cultured cell viability was assessed following treatment (48 hours) with (0 to 40 microM) alone or combination mitoxantrone. Synergism antagonism observed when combining calculated using CalcuSyn software (Biosoft). In addition, inhibition human xenograft growth vivo combined chemotherapy. Harvested tumors were immunohistochemical stained p27kip Ki67.Rh2...
Abstract Glioblastoma multiforme (GBM) is an aggressive type of brain tumor where <3% newly diagnosed cases in the patients will survive >5 years. In adults, GBM most common tumor. It rarer children, it constitutes ∼15% all tumors diagnosed. These are often invasive, making surgical resection difficult. Further, they can be refractory to current therapies such as temozolomide. The dogma that temozolomide resistance rests on expression O6-methylguanine-DNA methyltransferase...
Abstract Background Molecular subtyping has allowed for the beginning of personalized treatment in children suffering from medulloblastoma (MB). However, resistance inevitably emerges against these therapies, particularly Sonic Hedgehog (SHH) subtype. We found that with SHH subtype have worst outcome underscoring need to identify new therapeutic targets. Procedure High content screening a 129 compound library identified agents inhibited MB growth. Lead molecular target levels, p90 ribosomal...