- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Angiogenesis and VEGF in Cancer
- Molecular Biology Techniques and Applications
- Cancer, Lipids, and Metabolism
- Computational Drug Discovery Methods
- FOXO transcription factor regulation
- Hormonal and reproductive studies
- Melanoma and MAPK Pathways
- Nitric Oxide and Endothelin Effects
- Nuclear Receptors and Signaling
- Marine and coastal ecosystems
- Cancer Cells and Metastasis
- Analytical Chemistry and Chromatography
- Cholesterol and Lipid Metabolism
- Ubiquitin and proteasome pathways
- Extracellular vesicles in disease
- Mitochondrial Function and Pathology
- Veterinary Equine Medical Research
- Clusterin in disease pathology
- Enzyme function and inhibition
- Lipid metabolism and disorders
- Cardiac Imaging and Diagnostics
University of British Columbia
2010-2017
// 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...
Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles progression remain poorly characterized. In this study, we define an androgen-repressed gene whose expression elevated during adaptation prostate tumors to androgen-targeted therapies (ATTs), subsequent...
Treatment-induced neuroendocrine transdifferentiation (NEtD) complicates therapies for metastatic prostate cancer (PCa). Based on evidence that PCa cells can transdifferentiate to other neuroectodermally-derived cell lineages in vitro, we proposed NEtD requires first an intermediary reprogramming metastable stem-like (CSCs) of a neural class and demonstrate several different AR+/PSA+ lines were efficiently reprogrammed to, maintained propagated as CSCs by growth androgen-free neural/neural...
Genomic alterations involving translocations of the ETS-related gene ERG occur in approximately half prostate cancer cases. These result aberrant, androgen-regulated production protein variants that directly contribute to disease development and progression. This study describes discovery characterization a new class small molecule antagonists identified through rational silico methods. are designed sterically block DNA binding by ETS domain thereby disrupt transcriptional activity. We...
Human androgen receptor (AR) is a hormone-activated transcription factor that an important drug target in the treatment of prostate cancer. Current small-molecule AR antagonists, such as enzalutamide, compete with androgens bind to steroid-binding pocket ligand-binding domain (LBD). In castration-resistant cancer (CRPC), resistance can manifest through AR-LBD mutations convert antagonists into agonists, or by expression variants lacking LBD. Such underscores importance novel ways targeting...
Abstract The development of new antiandrogens, such as enzalutamide, or androgen synthesis inhibitors like abiraterone has improved patient outcomes in the treatment advanced prostate cancer. However, due to drug resistance and tumor cell survival, a majority these patients progress refractory state castration-resistant cancer (CRPC). Thus, newer therapeutic agents better understanding their mode action are needed for treating CRPC patients. We demonstrated previously that targeting Binding...
Like most teleosts, sablefish (Anoplopoma fimbria Pallas 1814) blood exhibits a moderate Root effect (~35% maximal desaturation), where reduction in pH dramatically reduces O(2) carrying capacity, mechanism important for oxygenating the eye and filling swim bladder (SB) teleosts. Although lack SB, we observed well-defined choroid rete at eye. The adrenergically mediated cell swelling typically associated with functional red (RBC) beta-adrenergic Na(+)/H(+) exchanger (betaNHE), which would...
Purpose Angiopoietin-like 4 (ANGPTL4) is known to play a variety of roles in the response exercise, and more recently has been shown enhance healing tendon, fibrous load-bearing tissue required for efficient movement. The objective current study was further explore mechanisms ANGPTL4's effect on tendon cells using gene array approach. Methods Human fibroblasts were treated with recANGPTL4 their global transcriptome analyzed after 24 h. We also conducted functional studies derived from human...
Clusterin (CLU) is a chaperone-like protein and plays protective role against renal ischemia-reperfusion injury (IRI); however, the molecular pathways for its functions in kidney are not fully understood. This study was designed to investigate CLU-mediating cells by using bioinformatics analysis. CLU null tubular epithelial (TECs) expressing human cDNA (TEC-CLU(hCLU) ) or empty vector (TEC-CLU(-/-) were exposed normoxia hypoxia (1% O2 ). Transcriptome profiling with significant twofold...
VOLUME 289 (2014) PAGES 26417–26429 A symbol was omitted to designate that Drs. Artem Cherkasov and Paul S. Rennie are equal senior authors.
Abstract The androgen receptor (AR) is a hormone-activated transcription factor implicated in the development and progression of prostate cancer. AR contains an N-terminal domain (NTD), followed by DNA binding (DBD) ligand-binding (LBD) domains. Upon androgens to LBD, moves into nucleus where it interacts with target genes via conserved AR-DBD. Prostate cancer treatment involves use small-molecules block production or compete for AR-LBD. Drug-resistance occurs when LBD mutations render...
Abstract Aims: Androgen-targeted therapies (ATTs) are the mainstay treatment for metastatic prostate cancer (PCa). However, ATTs promote adaptation of tumour cells and lead to castration resistant disease (CRPC). We have recently identified cell surface receptor, Neuropilin-1 (NRP1) as increased during EMT in CRPC. role NRP1 epithelium is poorly understood. This study aims determine whether inhibition will be a feasible therapeutic strategy blocking PCa metastasis therapy resistance....
Abstract Genomic alterations involving translocations of the ETS-related gene ERG occur in approximately half prostate cancer cases. These result aberrant, androgen-regulated production protein variants that directly contribute to disease development and progression. This study describes discovery characterization a new class small molecule antagonists identified through rational silico methods. are designed sterically block DNA binding by ETS domain thereby disrupt transcriptional activity....
Abstract Prostate cancer (PCa) is one of the leading causes cancer-related death in men worldwide. The common treatment option for recurring and advanced PCa focuses on inhibiting androgen receptor (AR). Unfortunately, despite an initial response to this treatment, drug resistance occurs, relapses incurable, castration-resistant form; thus, there a pressing need new therapeutics. Previous research has shown that up 50% all prostate cases, cause disease may be attributed genomic...
Abstract The androgen receptor (AR) is a hormone inducible transcription factor that continues to be an important drug-target prevent or slow the progression of prostate cancer. Current small molecule inhibitors, such as Enzalutamide (anti-androgens), compete with naturally occurring steroids bind binding pocket AR ligand domain (LBD). In advanced castration resistant cancer (CRPC), mutations in LBD confer drug-resistance by converting anti-androgens into agonists, prompting research develop...
<p>Supplementary Table S1: Cloning and RT-PCR primers used in this study; Supplementary Figure Luciferase cell viability experiments with MR49C PC3 cells; S2: ITC control experiment between AR-DBD dsDNA; S3: ChIP-PCR analysis; S4: Quality for ChIP experiments</p>
<p>Supplementary Table S1: Cloning and RT-PCR primers used in this study; Supplementary Figure Luciferase cell viability experiments with MR49C PC3 cells; S2: ITC control experiment between AR-DBD dsDNA; S3: ChIP-PCR analysis; S4: Quality for ChIP experiments</p>
<div>Abstract<p>Human androgen receptor (AR) is a hormone-activated transcription factor that an important drug target in the treatment of prostate cancer. Current small-molecule AR antagonists, such as enzalutamide, compete with androgens bind to steroid-binding pocket ligand–binding domain (LBD). In castration-resistant cancer (CRPC), resistance can manifest through AR-LBD mutations convert antagonists into agonists, or by expression variants lacking LBD. Such underscores...