A5049570974- Cancer Cells and Metastasis
- Bone health and treatments
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Chronic Lymphocytic Leukemia Research
- Metastasis and carcinoma case studies
- Biochemical and Molecular Research
- Acute Lymphoblastic Leukemia research
- Bone Metabolism and Diseases
- Gene expression and cancer classification
- Wnt/β-catenin signaling in development and cancer
- Advanced Proteomics Techniques and Applications
- Cancer-related molecular mechanisms research
- Protease and Inhibitor Mechanisms
- Skin and Cellular Biology Research
- Proteoglycans and glycosaminoglycans research
- Radiopharmaceutical Chemistry and Applications
- Cancer-related Molecular Pathways
- Redox biology and oxidative stress
- Peptidase Inhibition and Analysis
- Heat shock proteins research
- MicroRNA in disease regulation
- Cancer Research and Treatments
- Bone and Dental Protein Studies
Monash Health
2018-2023
Monash University
2011-2023
St Vincents Institute of Medical Research
2006-2020
St Vincent's Hospital
2003-2020
The University of Melbourne
2003-2020
Queensland University of Technology
2017-2019
British Heart Foundation
2014
King's College London
2014
The University of Queensland
1986-2011
Monash Institute of Medical Research
2011
Because most potential molecular markers and targets are proteins, proteomic profiling is expected to yield more direct answers functional pharmacological questions than does transcriptional profiling. To aid in such studies, we have developed a protocol for making reverse-phase protein lysate microarrays with larger numbers of spots previously feasible. Our first application these arrays was the 60 human cancer cell lines (NCI-60) used by National Cancer Institute screen compounds...
Abstract Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence severity, few effective therapies exist. To address this, we examined whether heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast bone. Utilizing human subline, MDA-MB-231SA, previously vivo selected for enhanced ability generate...
The progression of several cancers is correlated with the increased synthesis glycosaminoglycan, hyaluronan. Hyaluronan synthesized at plasma membrane by various isoforms hyaluronan synthases (HAS). importance HAS2 expression in highly invasive breast cancer was characterized antisense inhibition (ASHAS2). effect on cell proliferation, migration, metabolism, and receptor status vitro, whereas tumorigenicity metastasis established vivo. resulted a 24-hour lag proliferation that concomitant to...
Dynamic interconversions between transitional epithelial and mesenchymal states underpin the plasticity (EMP) seen in some carcinoma cell systems. We have delineated subpopulations existing within PMC42-LA breast cancer line by their EpCAM expression. These purified but phenotypically plastic states, EpCAMHigh (epithelial) EpCAMLow (mesenchymal), ability to regain phenotypic equilibrium of parental population (i.e., 80% 20% mesenchymal) over time, although rate reversion direction...
Abstract Using tissue whole exome sequencing (WES) and circulating tumor cell–free DNA (ctDNA), this Australasian Leukaemia & Lymphoma Group translational study sought to characterize primary acquired molecular determinants of response resistance marginal zone lymphoma (MZL) zanubrutinib for patients treated in the MAGNOLIA clinical trial. WES was performed on baseline samples obtained from 18 patients. For 7 patients, ctDNA sequence interrogated using a bespoke hybrid-capture...
Epithelial-to-mesenchymal transition (EMT) is associated with downregulated E-cadherin and frequently decreased proliferation. Proliferation may be restored in secondary metastases by mesenchymal-to-epithelial (MET). We tested whether maintains epithelial proliferation MDA-MB-468 breast cancer cells, facilitating metastatic colonization severe combined immunodeficiency (SCID) mice.EMT/MET markers were assessed xenograft tumors immunohistochemistry. Stable manipulation was effected...
The normal process of epithelial mesenchymal transition (EMT) is subverted by carcinoma cells to facilitate metastatic spread. Cancer rarely undergo a full conversion the phenotype, and instead adopt positions along epithelial-mesenchymal axis, propensity we refer as plasticity (EMP). EMP associated with increased risk metastasis in breast cancer consequent poor prognosis. Drivers towards state malignant include growth factor stimulation or exposure hypoxic conditions.We have examined two...
Two-dimensional gel electrophoresis with subsequent analysis by mass spectrometry was applied to study differences in protein expression between benign and malignant solid tumors from human beast, lung ovary cells. Cells freshly resected clinical material were lysed the extracts subjected isoelectric focusing immobilized pH gradients followed second-dimensional separation on 10—13% sodium dodecyl sulfate (SDS)/polyacrylamide gels. Polypeptides identified using matrix-assisted laser...
In order to find more effective anticancer drugs, the U.S. National Cancer Institute (NCI) screens a large number of compounds in vitro against 60 human cancer cell lines from different organs origin. About 70,000 have been tested program since 1990, and each compound can be characterized by vector (i.e., "fingerprint") activity, or -[log(GI50)], values. GI50 is concentration required inhibit growth 50% compared with untreated controls. Although inhibitory activity for single line not very...
Previous studies suggest that dihydrofolate reductase (DHFR) regulates its own translation. Moreover, intracellular levels of DHFR protein increase following exposure to the antifolate methotrexate (MTX), suggesting MTX may release translational inhibition mediated by [Chu et al. (1993) Biochemistry 32, 4756−4760; Ercikan Adv. Exp. Med. Biol. 338, 537−540]. To further investigate role in autoregulation, we have considered possibility directly contacts cognate mRNA. Binding using a series...
In the last six years, Developmental Therapeutics Program (DTP) of US National Cancer Institute (NCI) has screened over 60,000 chemical compounds and a larger number natural product extracts for their ability to inhibit growth 60 different cancer cell lines representing organs origin. Whereas inhibition one type gives no information on drug specificity, relative inhibitory activities against cells constitute patterns that encode detailed mechanisms action resistance (as reviewed in Boyd...
Abstract The ability to activate pro-matrix metalloproteinase (pro-MMP)-2 via membrane type-MMP is a hallmark of human breast cancer cell lines that show increased invasiveness, suggesting MMP-2 contributes progression. To investigate this, we have stably transfected pro-MMP-2 into the line MDA-MB-231, which lacks expression but does express its surface activator, type 1-MMP. Multiple clones were derived and shown produce it in response concanavalin A. In vitro analysis showed...