A5077159167- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- BRCA gene mutations in cancer
- Cancer Research and Treatments
- Molecular Biology Techniques and Applications
- Genomics and Chromatin Dynamics
- Lymphatic System and Diseases
- Endoplasmic Reticulum Stress and Disease
- Cancer-related molecular mechanisms research
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Cell death mechanisms and regulation
- Cancer Cells and Metastasis
- RNA modifications and cancer
- RNA Research and Splicing
- Cell Image Analysis Techniques
- CRISPR and Genetic Engineering
- Nutrition, Genetics, and Disease
- Cancer, Lipids, and Metabolism
- Genomic variations and chromosomal abnormalities
- Protein Degradation and Inhibitors
- Cytokine Signaling Pathways and Interactions
Hunter Medical Research Institute
2014-2024
University of Newcastle Australia
2015-2024
Calvary Mater Newcastle Hospital
2008-2023
Hunter Cancer Research Alliance
2020
Newcastle University
2020
John Hunter Hospital
2010-2014
Hunter Genetics
2013
UNSW Sydney
2012
Mater Misericordiae Hospital
2008
Epigenetic alterations in the cancer methylome are common breast and provide novel options for tumour stratification. Here, we perform whole-genome methylation capture sequencing on small amounts of DNA isolated from formalin-fixed, paraffin-embedded tissue triple-negative (TNBC) matched normal samples. We identify differentially methylated regions (DMRs) enriched with promoters associated transcription factor binding sites hypersensitive sites. Importantly, stratify TNBCs into three...
Abstract We have previously shown that most melanoma cell lines are insensitive to endoplasmic reticulum (ER) stress–induced apoptosis, and this involves activation of the mitogen-activated protein/extracellular signal-regulated kinase (MEK)/ERK signaling pathway expression apoptosis repressor with caspase recruitment domain (ARC) protein in cells. In present study, we show up-regulation antiapoptotic Bcl-2 family member Mcl-1 is another mechanism critical for protection cells against ER...
Abstract Purpose: Metastatic melanoma is largely unresponsive to DNA-damaging chemotherapy agents, although WTp53 frequently detected. Several isoforms of p53 have been discovered, some which inhibit function. We therefore examined whether were present in and they may contribute aberrant function melanoma. Experimental Design: studied the expression subcellular localization its a panel human cell lines using Western blot, two-dimensional electrophoresis, reverse transcription-PCR. also...
Metastatic melanoma represents a major clinical problem. Its incidence continues to rise in western countries and there are currently no curative treatments. While mutation of the P53 tumour suppressor gene is common feature many types cancer, mutational inactivation uncommon; however, its function often appears abnormal.In this study whole genome bead arrays were used examine transcript expression target genes extracts from 82 metastases 6 cell lines, provide global assessment aberrant...
Breast cancer is the most common malignancy that develops in women, responsible for highest cancer-associated death rates. Triple negative breast cancers represent an important subtype have aggressive clinical phenotype, are associated with a higher likelihood of metastasis and not responsive to current targeted therapies. miRNAs emerged as attractive candidate molecular biomarkers treatment targets cancer, but their role progression triple remains largely unexplored. This study has...
Mutation of p53 is a common feature cancer. Breast cancer the most malignancy that develops in women; however, somatic mutation rare, suggesting becomes inactivated by other mechanisms. expressed as smaller isoforms, some which inhibit wild-type p53. There are no studies have examined relative expression all isoforms this disease. We analysed messenger RNA Δ40, Δ133, β and γ panel 6 breast cell lines, 148 cancers specimens 31 matched normal adjacent tissues semi-quantitative real-time...
Temozolomide (TMZ), a DNA alkylating agent used in the treatment of melanoma, is believed to mediate its effect by addition methyl group O6 position guanine DNA. Resistance may be part due activity O6-methylguanine-DNA transferase (MGMT). In present study, we show that sensitivity melanoma cells TMZ was dependent on their p53 status and levels MGMT. Analysis mechanisms underlying reduced viability showed no evidence for induction apoptosis even though marked seen TK6 lymphoma cells....
Resistance of melanoma cells to chemotherapeutics remains a major obstacle successful treatment once it has spread beyond locoregional sites. We report in this study that activation the unfolded protein response (UPR) is involved resistance two chemotherapeutic drugs, cisplatin (CDDP) and adriamycin, associated with glucose-regulated 78 (GRP78)-mediated inhibition caspase-4 -7. The UPR was constitutively activated cultured cell lines fresh isolates as evidenced by elevated expression levels...
Brain metastases are a devastating consequence of cancer and currently there no specific biomarkers or therapeutic targets for risk prediction, diagnosis, treatment. Here the proteome brain metastatic breast cell line 231-BR has been compared with that parental MDA-MB-231, which is also but organ selectivity. Using SILAC nanoLC-MS/MS, 1957 proteins were identified in reciprocal labeling experiments 1584 quantified two lines. A total 152 confidently determined to be up- down-regulated by more...
Abstract Triple negative breast cancer (TNBC) is the most aggressive subtype with worst prognosis and no targeted treatments. TNBC patients are more likely to develop metastases relapse than other subtypes. We aimed identify TNBC-specific genes associated lymph node metastasis, one of first signs metastatic spread. A total 33 TNBCs were used; 17 which had matched normal adjacent tissues available 15 metastases. Gene expression microarray analysis was used reveal that differentially expressed...
Abstract Triple negative breast cancer (TNBC) is the most aggressive subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes altered expression comparing tumour to normal samples. This aimed establish whether DNA methylation contributed these changes in same cohort as well disease progression from primary lymph node metastasis associated epigenome. We obtained 23 TNBC samples, 12 matched metastases, and 11 adjacent tissues assayed for differential...
Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions copy number variation (CNV) associated metastasis in TNBC patients. CNV analyses were performed cohort 23 invasive ductal carcinomas (IDCs), 12 metastases (LNmets), 7 normal adjacent tissues (NATs); as well an independent containing 70 IDCs same NATs. CNV-associated genes analyzed using GO-enrichment...
Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that classified as benign, borderline, or malignant. As little is known about molecular underpinnings PTs, current diagnosis relies on histological examination. However, accurate classification often difficult, particularly for distinguishing borderline from malignant PTs. Furthermore, PTs can be misdiagnosed other tumour types with shared features, such fibroadenoma and metaplastic cancers. DNA methylation a recognised...
Abstract Background Tandem repeats (TRs) are unstable regions commonly found within genomes that have consequences for evolution and disease. In humans, polymorphic TRs known to cause neurodegenerative neuromuscular disorders as well being associated with complex diseases such diabetes cancer. If present in upstream regulatory regions, can modify chromatin structure affect transcription; resulting altered gene expression protein abundance. The most common short tandem (STRs), or...
Breast cancer is the most common malignancy in women world-wide. Triple negative breast (TNBC) a highly aggressive subtype that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor 2; associated with high propensity metastatic spread. Several studies have identified critical roles microRNAs cancer, but role two enzymes involved microRNA biogenesis, Dicer Drosha, not well understood, particularly respect to progression this subtype. We examined...
Are any microRNAs (miRNAs) that target the placental renin-angiotensin system (RAS) in human placenta suppressed early gestation?Overall, 21 miRNAs with predicted RAS mRNA targets were less abundant versus term placentae and nine more highly expressed.Regulation of expression could alter development therefore normal pregnancy outcome. The genes encoding prorenin (REN), angiotensinogen, (pro)renin receptor, angiotensin converting enzyme 2, II type 1 receptor are highest gestation, at a time...
We investigated the influence of selected TP53 SNPs in exon 4 and intron on cancer risk, clinicopathological features expression isoforms. The were significantly over-represented cohorts mixed cancers compared to three ethnically matched controls, suggesting they confer increased risk. Further analysis showed that heterozygosity at rs1042522(GC) either two intronic rs9895829(TC) rs2909430(AG) a 2.34-5.35-fold greater risk developing cancer. These SNP combinations found be associated with...
Breast cancer is the most diagnosed malignancy in women, with over half a million women dying from this disease each year. In our previous studies, ∆40p53, an N‐terminally truncated p53 isoform, was found to be upregulated breast cancers, and high ∆40p53 : p53α ratio linked worse disease‐free survival. Although inhibits migration invasion, little known about role of regulating these metastasis‐related processes its contributing prognosis. The aim study assess invasion. A relationship between...
The molecular changes involved in the induction of apoptosis by vincristine melanoma have not yet been well defined. Two human cell lines showing moderate (Mel-RM) and high (IgR3) sensitivity to were selected from a panel eight for analysis. Induction was caspase dependent, associated with increases mitochondrial membrane permeability. Vincristine upregulated expression Bax, Bak, PUMA, Noxa, p53 p21 proteins, downregulated and/or phosphorylated Bcl-2 protein. Inhibitors Jun N-terminal kinase...
Abstract Two of the hallmark features melanoma are its development as a result chronic UV radiation exposure and limited efficacy cisplatin in disease treatment. Both these DNA-damaging agents large helix-distorting DNA damage that is recognized repaired by nucleotide excision repair (NER). The aim this study was to examine expression NER gene transcripts, p53, p21 cell lines treated with compared melanocytes. Basal all genes greater Global genome (GGR) transcripts showed significantly...