A5069483170- Estrogen and related hormone effects
- Cancer-related Molecular Pathways
- Growth Hormone and Insulin-like Growth Factors
- Cancer, Hypoxia, and Metabolism
- Cell death mechanisms and regulation
- HER2/EGFR in Cancer Research
- Metabolism, Diabetes, and Cancer
- Genetic factors in colorectal cancer
- Urological Disorders and Treatments
- Cancer Cells and Metastasis
- Computational Drug Discovery Methods
- Breast Cancer Treatment Studies
- Global Cancer Incidence and Screening
- Heat shock proteins research
- Digestive system and related health
- Phytochemistry and Biological Activities
- Pediatric Urology and Nephrology Studies
- Bioinformatics and Genomic Networks
- Toxin Mechanisms and Immunotoxins
- Kidney Stones and Urolithiasis Treatments
- Cancer Genomics and Diagnostics
- Abdominal Trauma and Injuries
- Pancreatic and Hepatic Oncology Research
- Ginseng Biological Effects and Applications
- Sphingolipid Metabolism and Signaling
UNSW Sydney
2005-2020
Biostatistical Consulting (United States)
2019
Kaiser Permanente
2019
Garvan Institute of Medical Research
2005-2016
St Vincent's Hospital
2005-2016
National Breast Cancer Foundation
2014-2015
University of Pittsburgh
2013
The Kinghorn Cancer Centre
2013
St Vincent's Clinic
2006-2013
Camden and Campbelltown Hospitals
2011
We report that transfection of insulin-like growth factor-binding protein-3 (IGFBP-3) cDNA in human breast cancer cell lines expressing either mutant p53 (T47D) or wild-type (MCF-7) induces apoptosis. IGFBP-3 also increases the ratio pro-apoptotic to anti-apoptotic members Bcl-2 family. In MCF-7, an increase Bad and Bax protein expression a decrease Bcl-x<sub>L</sub> mRNA were observed. T47D, proteins up-regulated; is undetectable these cells. As T47D expresses protein, modulations induction...
The ICE/CED-3 family of proteases (caspases) play a central role in the execution phase apoptosis. These are synthesised as precursor molecules that require processing at specific aspartate residues to produce two subunits comprise active enzyme. activation some these has been shown occur during Here we show Nedd2/ICH-1 (caspase-2) is activated apoptosis induced by variety apoptotic stimuli. This occurs very early upon treatment cells with agents and appears precede CPP32 (caspase-3). Nedd2...
The role of insulin-like growth factor-binding protein (IGFBP)-5 in human breast cancer cell is unclear. We determined the effects IGFBP-5 expression on lines vivo and vitro. Expression IGFBP-5, both by stable transfection adenoviral-mediated infection, was inhibitory to MDA-MB-231 Hs578T cells over a 13-day period. resulted G2/M cycle arrest induction apoptosis lines, an effect that abrogated presence broad-spectrum caspase inhibitor, z-VAD-fmk. IGFBP-5-induced associated with...
Estrogen is a pivotal regulator of cell proliferation in the normal breast and cancer. Endocrine therapies targeting estrogen receptor are effective cancer, but their success limited by intrinsic acquired resistance. With goal gaining mechanistic insights into action endocrine resistance, we classified estrogen-regulated genes function, determined relationship between functionally-related genesets response to tamoxifen cancer patients. Estrogen-responsive were identified transcript profiling...
Nedd2 (caspase-2) is a cysteine protease of the caspase family that has been demonstrated to play role in apoptotic pathway. The 51-kDa precursor undergoes cleavage into two subunits following various stimuli. In this study, we have investigated dimerization (pro-Nedd2) Saccharomyces cerevisiae and its self-processing activity vivo. We demonstrate expression pro-Nedd2 yeast cells results processing precursor. A catalytically inactive mutant dimerized yeast, required both prodomain...
IGF-binding protein-3 (IGFBP-3) has both antiproliferative and proapoptotic effects on the growth of human breast cancer cells in vitro. However, mechanisms governing these are not well understood. IGFBP-3 been shown to associate with cell surface through carboxyl-terminal residues. This suggests that it may interact a specific receptor, although signaling receptor for yet fully characterized. also translocates nucleus nuclear RXRα, evidence this interaction mediate its inhibitory effects....
Objective: To evaluate the impact of National Breast Cancer Foundation's (NBCF's) research investment. Design and participants: Surveys based on Payback Framework were sent to chief investigators involved in funded by NBCF during 1995–2012; a bibliometric analysis NBCF-funded publications 2006–2010 was conducted; purposive, stratified sample case studies obtained. Main outcome measures: Research knowledge production, system, informing policy, product development broader health economic...
Abstract IGF binding protein (IGFBP)-3 has antiproliferative and proapoptotic effects on the growth of human breast cancer cells in vitro. However, clinical studies suggest that high levels IGFBP-3 tumor tissue are associated with large, highly proliferative tumors. In this study, we examined stable transfection cDNA T47D vitro vivo. Expression initially inhibited but was enhanced Furthermore, IGFBP-3-expressing became stimulated at higher passages post transfection, suggesting may switch...
Abstract Phytochemicals have provided an abundant and effective source of therapeutics for the treatment cancer. Here we describe characterization a novel plant toxin, persin, with in vivo activity mammary gland p53-, estrogen receptor–, Bcl-2-independent mode action. Persin was previously identified from avocado leaves as toxic principle responsible gland–specific necrosis apoptosis lactating livestock. used mouse model to confirm that persin has similar cytotoxicity epithelium. Further...
Acquired resistance to the anti-estrogen tamoxifen remains a significant challenge in breast cancer management. In this study, we used an integrative approach characterize global protein expression and tyrosine phosphorylation events tamoxifen-resistant MCF7 cells (TamR) compared with parental controls. Quantitative mass spectrometry computational approaches were combined identify perturbed signalling networks, candidate regulatory proteins functionally interrogated by siRNA-mediated...
APC (adenomatous polyposis coli) protein is differentially expressed in the normal colonic crypt and believed to be involved cell maturation. In this work we investigated whether expression of associated with death epithelial cells. We have previously reported an vitro system study apoptosis. Briefly, cells attached flask a low frequency apoptosis (1-3%), whereas that detach from float medium high proportion apoptotic (36-96% depending on line). The full-length 300-kDa or truncated protein,...
Sodium butyrate (NaBt) and the pro-apoptotic IGFBP-3 protein, expressed at top of normal colonic crypt, have both been implicated in regulation apoptosis epithelial cells. Recent studies human breast hepatic cell lines shown that NaBt can transcriptionally upregulate expression. However, role expression colon is less clear, with reports up- downregulation protein colorectal cancer lines. In this study we level cells correlates p53 status cells; wildtype secrete higher levels IGFBP3 than...
Expression of IGF-binding protein-3 (IGFBP-3) and IGFBP-5 in human breast cancer cells induces apoptosis is associated with modulations Bcl-2 proteins, suggesting that these IGFBPs induce an intrinsic apoptotic pathway. In this study we demonstrate although both induced the activation caspase-8 caspase-9, expression IGFBP-5, but not IGFBP-3, sensitized MDA-MB-231 to inhibitory effects TNFalpha. This sensitivity TNFalpha was a block nuclear factor-kappaB-mediated cell survival signals. also...
BAG-1 (bcl-2-associated athanogene) enhances oestrogen receptor (ER) function and may influence outcome response to endocrine therapy in breast cancer. We determined relationships between expression, molecular phenotype, tamoxifen a cohort of cancer patients its on sensitivity MCF-7 cells vitro. Publically available gene expression data sets were analysed identify mRNA patient outcome. protein was assessed using immunohistochemistry 292 with invasive ductal carcinoma correlated...
Estrogens play a pivotal role in the initiation and progression of breast cancer. The genes that mediate these processes are not fully defined, but potentially include known mammary oncogene MYC. Characterization estrogen-target may help to elucidate further mechanisms estrogen-induced mitogenesis endocrine resistance.We used transcript profiling approach identify targets estrogen c-Myc cancer cells. One previously uncharacterized gene, namely HBV pre-S2 trans-regulated protein 3 (HSPC111),...
Abstract Phytochemicals have provided an abundant source of novel therapeutics for the treatment human cancers. We previously described a plant toxin, persin, derived from avocado leaves, which has unique in vivo actions mammary epithelium and Bim-dependent, cytotoxic effects breast cancer cells vitro. Compounds structurally similar to such as polyunsaturated fatty acid, conjugated linoleic can attenuate steroid hormone receptor signaling modulate response antiestrogens. Here, we provide...