A5101825863- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Caveolin-1 and cellular processes
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- Animal Virus Infections Studies
- Estrogen and related hormone effects
- Growth Hormone and Insulin-like Growth Factors
- PI3K/AKT/mTOR signaling in cancer
- Radiopharmaceutical Chemistry and Applications
- Bone health and treatments
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related Molecular Pathways
- Cholesterol and Lipid Metabolism
- Hormonal and reproductive studies
- Parathyroid Disorders and Treatments
- Metabolism, Diabetes, and Cancer
- Hedgehog Signaling Pathway Studies
- Immunotherapy and Immune Responses
- Cell death mechanisms and regulation
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- Cancer-related molecular mechanisms research
- Cell Adhesion Molecules Research
University of British Columbia
2015-2024
Vancouver Coastal Health Research Institute
2011-2023
Vancouver Coastal Health
2007-2023
University of Florida Health
2020
University of Florida
2020
American College of Surgeons
2020
University of Naples Federico II
2018
Vancouver General Hospital
2006-2017
The Prostate Centre
2006-2017
Mercy Medical Center
2015
Abstract Hormone-driven expression of the ERG oncogene after fusion with TMPRSS2 occurs in 30% to 70% therapy-naive prostate cancers. Its relevance castration-resistant cancer (CRPC) remains controversial as is not expressed some TMPRSS2-ERG androgen-independent xenograft models. However, unlike these models, CRPC patients have an increasing prostate-specific antigen, indicating active androgen receptor signaling. Here, we collected blood every month from 89 (54 chemotherapy-naive and 35...
Standardized and reproducible preclinical models that recapitulate the dynamics of prostate cancer are urgently needed. We established a bank transplantable patient-derived xenografts capture biologic molecular heterogeneity currently confounding prognostication therapy development. Xenografts preserved histopathology, genome architecture, global gene expression donor tumors. Moreover, their aggressiveness matched patient observations, response to androgen withdrawal correlated with tumor...
Rho/ROCK signaling and caveolin-1 (Cav1) are implicated in tumor cell migration metastasis; however, the underlying molecular mechanisms remain poorly defined. Cav1 was found here to be an independent predictor of decreased survival breast rectal cancer significantly associated with presence distant metastasis for colon patients. promotes by regulating focal adhesion (FA) dynamics through tyrosine (Y14) phosphorylation Cav1. Phosphorylated is localized protrusive domains cells dependent on...
Abstract BACKGROUND Although recent laboratory and population studies suggest that prostate cancer may be responsive to insulin, there is a gap in knowledge concerning the expression of insulin receptors on benign or malignant tissue. METHODS We immunostained 644 cores tissue microarrays prepared from 29 samples without malignancies, 78 Gleason grade 3 cancers, 21 4 cancers 33 5 with antibodies against insulin‐like growth factor I receptor receptor. RESULTS observed immunoreactivity both...
Abstract Background and Purpose. Warm-up prior to static stretching enhances muscle extensibility. The relative effectiveness of different modes warm-up, however, is unknown. purpose this study was evaluate the superficial heat, deep active exercise warm-up compared with alone on extensibility plantar-flexor muscles. Subjects. Ninety-seven subjects (59 women, 38 men) limited dorsiflexion range motion (ROM) were randomly assigned 1 5 groups. Female had a mean age 27.6 years (SD=7.68,...
Background: Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes, ERG or ETV1 . Many cases have chromosomal rearrangements leading to fusion of 5′ end androgen-regulated serine protease TMPRSS2 (21q22.2) 3′ either (21q22.3) (7p21.3). The consequence these is aberrant androgen receptor-driven expression Aim: To determine frequency involving , genes in CaP varying Gleason grades through fluorescence situ hybridisation (FISH) on tissue microarrays...
Abstract Background The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well recurrence and death from cancer. These associations suggest hypothesis that may be used a prognostic indicator for Methods In this study, fluorescent situ hybridization (FISH) assays were to assess status group 214 cancer cases two population-based studies. FISH designed detect both type (deletion vs. translocation) number copies (single...
Neuroendocrine (NE) differentiation in prostatic adenocarcinomas has been reported to be an early marker for development of androgen independence. Secretion mitogenic peptides from nondividing NE cells is thought contribute a more aggressive disease by promoting the proliferation surrounding tumor cells. We undertook studies determine whether prostate cancer cell line LNCaP could induced acquire characteristics treatment with agents that are found complex environment which progression...
Abstract Apoptosis and inhibition of mitosis are primary mechanisms mediating androgen ablation therapy-induced regression prostate cancer (PCa). However, PCa readily becomes independent, leading to fatal disease. Up-regulated growth survival signaling is implicated in development resistance therapy. We testing the hypothesis that insulin-like factor (IGF) responsiveness required for androgen-independent (AI) progression. Using LNCaP human progression model, we have determined IGF-I–mediated...
Abstract Progression to androgen independence is the lethal end stage of prostate cancer. We used expression receptor (AR)-targeted short hairpin RNAs (shRNA) directly test requirement for AR in ligand-independent activation androgen-regulated genes and hormone-independent tumor progression. Transient transfection LNCaP human cancer cells showed that shRNA decreased R1881 induction prostate-specific antigen (PSA)-luciferase reporter by 96%, whereas forskolin, interleukin-6, or epidermal...
Neuroendocrine (NE) differentiation within prostate tumors is proposed to be a contributing factor in disease progression. However, the cellular origin and molecular mechanism controlling of prostatic NE cells are unresolved. The tumor cell line, LNCaP, can reversibly acquire many characteristics response treatment with beta-adrenergic receptor agonists activators adenylate cyclase. In this study, we demonstrate that these treatments induce protein kinase A (PKA) activation LNCaP ectopic...
The cytokine interleukin-10 (IL-10) potently inhibits macrophage function through activation of the transcription factor STAT3. expression SOCS3 (suppressor signaling-3) has been shown to be induced by IL-10 in a STAT3-dependent manner. However, relevance anti-inflammatory effect on macrophages controversial. Through kinetic analysis requirement for inhibition lipopolysaccharide (LPS)-stimulated tumor necrosis factor-α (TNFα) and translation, was found necessary TNFα during early phase, but...
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...
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...
Cannabinoids, the active components of Cannabis sativa Linnaeus, have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects and tumor regression, but use chemotherapy is limited by psychotropic activity. To date, cannabinoids been successfully used treatment nausea vomiting, two common side that accompany cancer patients. Most non-THC plant e.g. cannabidiol cannabigerol, seem be devoid properties....