A5080995949- Prostate Cancer Treatment and Research
- Prostate Cancer Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- Genetic factors in colorectal cancer
- Cancer Immunotherapy and Biomarkers
- Bladder and Urothelial Cancer Treatments
- Cancer-related molecular mechanisms research
- Molecular Biology Techniques and Applications
- Alzheimer's disease research and treatments
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- Urologic and reproductive health conditions
- Cancer, Hypoxia, and Metabolism
- Hormonal and reproductive studies
- Cancer-related Molecular Pathways
- Angiogenesis and VEGF in Cancer
- RNA Research and Splicing
- PARP inhibition in cancer therapy
- Cancer Cells and Metastasis
- Renal cell carcinoma treatment
- MicroRNA in disease regulation
- Wnt/β-catenin signaling in development and cancer
The University of Melbourne
2016-2025
Prostate Cancer Foundation of Australia
2016-2025
Epworth Hospital
2010-2025
The Royal Melbourne Hospital
2015-2024
Victorian Comprehensive Cancer Centre
2021-2024
Western Health
2024
Footscray Hospital
2024
Melbourne Bioinformatics
2022
Walter and Eliza Hall Institute of Medical Research
2020
Arizona State University
2018-2019
Abstract Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality poorly understood. Here we reveal precise direction metastatic spread across four lethal patients using whole-genome ultra-deep targeted sequencing longitudinally collected tumours. We find one case surgical bed causing local recurrence, another cross-metastatic site seeding combining with dynamic...
The AF-6/afadin protein, which contains a single PDZ domain, forms peripheral component of cell membranes at specialized sites cell-cell junctions. To identify potential receptor-binding targets AF-6 we screened the domain against range COOH-terminal peptides selected from receptors having domain-binding termini. interacts with subset members Eph subfamily RTKs via its COOH terminus both in vitro and vivo. Cotransfection green fluorescent protein-tagged fusion protein full-length into...
Traumatic brain injury is a common and serious neurodegenerative condition that lacks pharmaceutical intervention to improve long-term outcome. Hyperphosphorylated tau implicated in some of the consequences traumatic potential pharmacological target. Protein phosphatase 2A heterotrimeric protein regulates key signalling pathways, heterotrimers consisting PR55 B-subunit represent major brain. Here we investigated whether rats humans would induce changes phosphorylated tau, treatment with...
The Illumina HumanMethylation450 BeadChip (HM450K) measures the DNA methylation of 485,512 CpGs in human genome. technology relies on hybridization genomic fragments to probes chip. However, certain factors may compromise ability measure using array such as single nucleotide polymorphisms (SNPs), small insertions and deletions (INDELs), repetitive DNA, regions with reduced complexity. Currently, there is no clear method or pipeline for determining which HM450K bead should be retained...
Study Type – Prognosis (retrospective cohort) Level of Evidence 2b OBJECTIVE • To determine the effect an upgrade in Gleason score between initial prostate biopsy and final prostatectomy specimen on risk postoperative biochemical recurrence. PATIENTS AND METHODS A total 1629 patients with paired radical histology were identified from two prospectively recorded cancer databases. Information key clinical pathological characteristics as well prostate-specific antigen follow-up was recorded....
There are no treatments in clinical practice known to mitigate the neurobiological processes that convert a healthy brain into an epileptic one, phenomenon as epileptogenesis. Downregulation of protein phosphatase 2A, causes hyperphosphorylation tau, is implicated neurodegenerative diseases commonly associated with epilepsy, such Alzheimer's disease and traumatic injury. Here we used 2A activator sodium selenate investigate role three different rat models epileptogenesis: amygdala kindling,...
The objective of this study was to determine whether microRNA (miRNA) profiling urine could identify the presence urothelial carcinoma bladder (UCB) and compare its performance characteristics that cystoscopy.In discovery cohort we screened 81 patients, which included 21 benign controls, 30 non-recurrers patients with active cancer (recurrers), using a panel 12 miRNAs. Data analysis performed machine learning approach Support Vector Machine classifier Student's t-test feature selection...
Emerging data suggest that metastasis is a spectrum of disease burden rather than binary state, and local therapies, such as radiation, might improve outcomes in oligometastasis. However, current definitions oligometastasis are solely numerical. To characterize the somatic mutational landscape across metastatic castration-sensitive prostate cancer (mCSPC) to elucidate biological definition oligometastatic CSPC. This was retrospective study men with mCSPC who underwent clinical-grade...
Abstract Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as grade. To interrogate the evolutionary origins cancer heterogeneity, we analyzed 666 whole genomes. We identified a compendium 223 recurrently mutated driver regions, influencing downstream processes gene expression. validated individual germline variants that predispose tumors to acquire specific...
By using the polymerase chain reaction with degenerate oligonucleotides based on highly conserved motifs held in common between all members of protein tyrosine kinase (PTK) family, a PTK-related sequence was isolated from murine peritoneal macrophage cDNA. Full-length clones have been that encompass entire coding region mRNA, and predicted amino acid indicates encoded has structure growth factor receptor PTK (RTK). We dubbed this molecule RYK (for related to kinase). The RYK-encoded bears...
Transforming Growth Factor-β (TGF-β) and Epidermal Factor (EGF) signaling pathways are both independently implicated as key regulators in tumor formation progression. Here, we report that the tumor-associated overexpression of epidermal growth factor receptor (EGFR) desensitizes TGF-β its cytostatic regulation through specific persistent Stat3 activation Smad7 induction vivo. In human cell lines, reduction TGF-β-mediated Smad2 phosphorylation, nuclear translocation Smad3 target gene were...
The latency associated with bone metastasis emergence in castrate-resistant prostate cancer is attributed to dormancy, a state which cells persist prior overt lesion formation. Using single-cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor-intrinsic immune signaling retention cell dormancy. We demonstrate that loss type I IFN occurs proliferating bone. This suppresses tumor immunogenicity therapeutic response promotes activation drive progression....
Background: There is increasing interest in targeting hyperphosphorylated tau (h-tau) as a disease modifying approach for Alzheimer's (AD). Sodium selenate directly stimulates the activity of PP2A, main enzyme responsible h-tau dephosphorylation brain. Objective: This study ssessed safety and tolerability 24-week treatment with VEL015 (sodium selenate) AD. Investigating effects on cognitive, CSF, neuroimaging biomarkers AD were secondary, exploratory objectives. Data used to identify showing...
Abstract Background DNA originating from degenerate tumour cells can be detected in the circulation many types, where it used as a marker of disease burden well to monitor treatment response. Although circulating (ctDNA) measurement has prognostic/predictive value metastatic prostate cancer, its utility localised is unknown. Methods We performed whole-genome sequencing tumour-normal pairs eight patients with clinically undergoing prostatectomy, identifying high confidence genomic...
Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does study add? Due to sampling error, Gleason score clinically localized prostate cancer is frequently underestimated at time initial biopsy. Given that this may lead inappropriate surveillance patients with high‐risk disease, there considerable interest in identifying predictors significant undergrading. Recently PSAD has been proposed be an accurate predictor subsequent upgrading...
Study Type – Diagnostic (case series) Level of Evidence 4 What's known on the subject? and What does study add? The Gleason score prostate cancer is frequently underestimated at time diagnostic biopsy, although contribution sampling error to its incidence unknown. We show that under‐graded tumours are significantly smaller concordant for higher grade, indicating incomplete tumour plays a significant role in assignment error. OBJECTIVE To determine influence gland volumes underestimation core...