A5036742324- Ovarian cancer diagnosis and treatment
- TGF-β signaling in diseases
- Reproductive Biology and Fertility
- Advanced biosensing and bioanalysis techniques
- Growth Hormone and Insulin-like Growth Factors
- Endometrial and Cervical Cancer Treatments
- Cancer Genomics and Diagnostics
- Kruppel-like factors research
- Pregnancy and preeclampsia studies
- Genetic Syndromes and Imprinting
- Cancer Cells and Metastasis
- BRCA gene mutations in cancer
- Renal and related cancers
- Molecular Junctions and Nanostructures
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Microtubule and mitosis dynamics
- Electrochemical Analysis and Applications
- RNA modifications and cancer
- Viral-associated cancers and disorders
- RNA Research and Splicing
- Pancreatic and Hepatic Oncology Research
- PARP inhibition in cancer therapy
Research Institute in Oncology and Hematology
2016-2024
CancerCare Manitoba
2014-2024
University of Manitoba
2014-2024
The Society of Obstetricians and Gynaecologists of Canada
2016
Victoria General Hospital
2016
Dalhousie University
2001-2011
Université de Sherbrooke
2006
University of California, San Francisco
1994-2001
Penn State Milton S. Hershey Medical Center
1976
Pennsylvania State University
1976
Recruitment of primordial follicles is essential for female fertility; however, the exact mechanisms regulating this process are largely unknown. Earlier studies using anti-Müllerian hormone (AMH)-deficient mice suggested that AMH involved in regulation follicle recruitment. We tested hypothesis a neonatal ovary culture system, which ovaries from 2-d-old C57Bl/6J were cultured 2 or 4 d absence presence AMH. Ovaries contain multiple follicles, some naked oocytes, and no at later stages...
Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, regulates the enzymes that produce sex steroids, and disruption of Ftz-F1 gene encoding SF-1 precludes adrenal gonadal development. We now study role at other levels hypothalamic/pituitary/gonadal axis. In Ftz-F1-disrupted mice, immunohistochemical analyses with antibodies against pituitary trophic hormones showed a selective loss gonadotrope-specific markers, supporting in gonadotrope function. situ hybridization confirmed these...
We identified previously an autocrine bone morphogenetic protein-4 (BMP4) signalling pathway in primary human normal ovarian surface epithelial (OSE) and cancer (OvCa) cells. Herein we show that treatment of OvCa cells with BMP4 produced morphological alterations increased cellular adhesion, motility invasion. The inhibitor noggin blocked the BMP4-induced phenotype, decreased BMP4-mediated cell adherence. In response to exogenous BMP4, epithelial–mesenchymal transition (EMT) markers Snail...
Ovarian carcinoma is the most lethal gynecological malignancy due to early dissemination and acquired resistance platinum-based chemotherapy. Reliable markers that are independent complementary clinical parameters needed improve management of patients with this disease. The Canadian Experimental Unified Resource (COEUR) provides researchers biological material associated data conduct biomarker validation studies. Using standards defined by Tissue Repository Network (CTRNet), we have...
During male gonadal development Müllerian duct regression is mediated by the actions of hormone inhibiting substance (MIS), a member transforming growth factor beta superfamily. MIS considered to be unique among members this superfamily because bioactivation via proteolytic processing hypothesized occur at its target organ, duct. We find instead that majority processed and secreted from embryonic testes as complex in which mature region remains noncovalently associated with prodomain. In...
Müllerian inhibitory substance (MIS), also known as anti-Müllerian hormone, is best the hormone that regulates regression of duct in males. In females, MIS expressed granulosa cells preantral and early antral follicles. The specific type II receptor present theca these small, growing Because role follicle development unknown, we have evaluated effect on growth, differentiation, apoptosis intact follicles a serum-free culture system. this system, treatment with FSH induces an increase both...
Adipogenesis is dependent on the sequential activation of transcription factors including CCAAT/enhancer-binding proteins (C/EBP), peroxisome proliferator-activated receptor γ (PPARγ), and steroid regulatory element-binding protein (SREBP). We show that mood stabilizing drug valproic acid (VPA; 0.5–2 mm) inhibits mouse 3T3 L1 human preadipocyte differentiation, likely through its histone deacetylase (HDAC) inhibitory properties. The HDAC inhibitor trichostatin A (TSA) also inhibited...
SUMMARY The effect of human cytomegalovirus (CMV) on cell DNA synthesis and mitotic activity in hamster embryo fibroblasts was examined. results indicated that CMV infected cells had increased rates replication activity. Detection the these two parameters necessitated arrest prior to infection with low serum concentrations. This lowered background levels division so virus could be detected. data indicate arrested demonstrate susceptibility infection. It also observed both enhanced by...
ObjectiveHigh-grade serous ovarian cancer (HGSOC) is the most lethal gynaecological malignancy in women with a high level of mortality, metastatic disease, disease recurrence and multi-drug resistance. Many previous studies have focused on characterising genome instability recurrent resistant HGSOC while this has advanced our understanding HGSOC, fundamental knowledge mechanisms driving remains limited. Chromosome (CIN; an increased rate chromosome gains losses) form that commonly associated...
Abstract Background High-grade serous ovarian cancer (HGSOC) is the most common and lethal histotype. Chromosome instability (CIN, an increased rate of chromosome gains losses) believed to play a fundamental role in development evolution HGSOC. Importantly, overexpression Cyclin E1 protein induces CIN, genomic amplification CCNE1 contributes HGSOC pathogenesis ~20% patients. levels are normally regulated cell cycle-dependent manner by SCF ( S KP1– C UL1– F BOX) complex, E3 ubiquitin ligase...
Epithelial ovarian cancer (EOC) is the most prevalent form of and has highest mortality rate. Novel insight into EOC required to minimize morbidity rates caused by recurrent, drug resistant disease. Although numerous studies have evaluated genome instability in EOC, none addressed putative role chromosome (CIN) disease progression resistance. CIN defined as an increase rate at which whole chromosomes or large parts thereof are gained lost, can only be using approaches capable characterizing...
Inherent or acquired drug resistance is a major contributor to epithelial ovarian cancer (EOC) mortality. Novel drugs combinations that produce EOC cell death resensitize resistant cells standard chemotherapy may improve patient treatment. After conducting tolerability studies for the multikinase inhibitors dorsomorphin (DM) and it structural analogue LDN-193189 (LDN), these were tested in mouse intraperitoneal xenograft model of EOC. DM significantly increased survival, whereas LDN showed...
Five members of the human growth hormone (GH) gene family are located at a single locus on chromosome 17. Growth is expressed in pituitary under control tissue-specific factor Pit 1/GHF-1, and chorionic somatomammotropin (CS) -A, -B, -L, as well placental GH variant, specifically syncytiotrophoblast. Despite this specificity vivo, CS-A promoter can bind 1/GHF-1 allow activity tumor cells after transfer. We have identified characterized PSF sequences associated with only GH/CS which repress >...
Bone morphogenetic proteins (BMPs) are members of the TGFbeta superfamily cytokines that involved in development, differentiation, and disease. In an analysis normal ovarian surface epithelium (OSE) cancer (OC) cells, we observed BMP4 mRNA expression found primary OC cells produce mature BMP4. addition, each member downstream signaling pathway was expressed OSE cells. Smad1 phosphorylated underwent nuclear translocation upon treatment with Interestingly, BMP target genes ID1 ID3 were...
Treatment of epilepsy or bipolar disorder with valproic acid (VPA) induces weight gain and increased serum levels for the satiety hormone, leptin, through an unidentified mechanism. In this study we tested effects VPA, a short-chain branched fatty (C8:0), on leptin biology metabolism in 3T3-L1 adipocytes. VPA significantly reduced secretion dose-dependent manner. Because accumulation has been hypothesized to block secretion, effect metabolism. Using 14C-radiolabeled found that 14C was mainly...
To evaluate whether hormone therapy (HT) after nonserous epithelial ovarian cancer is associated with a decrease in overall and disease-free survival.We conducted retrospective cohort study. The Manitoba Cancer Registry Drug Programs Information Network were searched to find all women known ovarian, fallopian tube, or primary peritoneal between 1995 2010 who had used HT treatment. Women did not receive treatment no follow-up excluded.Three hundred ninety-one patients met the inclusion...