A5078921079- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Cancer Cells and Metastasis
- Prostate Cancer Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Heat shock proteins research
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Metabolomics and Mass Spectrometry Studies
- Estrogen and related hormone effects
- Cancer Genomics and Diagnostics
- Tissue Engineering and Regenerative Medicine
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- BRCA gene mutations in cancer
- Xenotransplantation and immune response
- Molecular Biology Techniques and Applications
- Adipose Tissue and Metabolism
- CAR-T cell therapy research
- Genetic Associations and Epidemiology
- Protein Degradation and Inhibitors
- Adipokines, Inflammation, and Metabolic Diseases
- Hormonal and reproductive studies
- Historical and Scientific Studies
- Cardiovascular Disease and Adiposity
Monash University
2016-2025
Peter MacCallum Cancer Centre
2004-2025
The University of Melbourne
2006-2025
Australian Regenerative Medicine Institute
2013-2024
Cabrini Hospital
2022-2024
National Acoustic Laboratories
2024
The University of Sydney
2024
Discovery Institute
2018-2022
Austin Health
2022
John Wiley & Sons (United States)
2017-2021
Prostate cancer depends on fatty acid uptake and remodeling of the prostate lipidome, blocking impairs tumorigenesis.
Abstract Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and aggressive disease. To understand this aggression, here we profile genomes methylomes localized PCa from 14 carriers deleterious germline ( -mutant PCa). We show that harbour genomic instability a mutational more closely resembles metastastic than shows epigenomic dysregulation MED12L / MED12 axis, which is frequently dysregulated metastatic...
Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent diseases commonly treated by inhibiting androgen action. However, ablation or castration fail to target androgen-independent cells implicated in disease etiology recurrence. Mechanistically different castration, this study shows beneficial proapoptotic actions of estrogen receptor–β (ERβ) BPH PCa. ERβ agonist induces apoptosis stromal, luminal castrate-resistant basal epithelial estrogen-deficient aromatase...
Adipocyte progenitor cells (APCs) provide the reservoir of regenerative to produce new adipocytes, although their identity in humans remains elusive. Using FACS analysis, gene expression profiling, and metabolic proteomic analyses, we identified three APC subtypes human white adipose tissues. The are molecularly distinct but possess similar proliferative adipogenic capacities. Adipocytes derived from APCs with high CD34 exhibit exceedingly rates lipid flux compared low or no expression,...
The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium the surrounding microenvironment. To date, molecular profiling has largely been restricted to epithelial component tumors; therefore, features underpinning persistent protumorigenic phenotype tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for first time that cancer-associated fibroblasts (CAFs) from localized prostate display remarkably distinct enduring...
In prostate cancer, cancer-associated fibroblasts (CAF) exhibit contrasting biological properties to non-malignant (NPF) and promote tumorigenesis. Resolving intercellular signaling pathways between CAF tumor epithelium may offer novel opportunities for research translation. To this end, the proteome phosphoproteome of four pairs patient-matched NPF were characterized identify discriminating proteomic signatures. Samples analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
Targeting Hsp90 has significant potential as a treatment for prostate cancer, but prototypical agents such 17-allylamino-17 demethoxygeldanamycin (17-AAG) have been ineffective in clinical trials. Recently, phase I study aimed at defining biologically active dose reported the first response to an inhibitor patient with which supports development of new generation compounds this disease.The biological actions two synthetic inhibitors, NVP-AUY922 and NVP-HSP990, were evaluated cancer cell...
Normal prostatic epithelium is composed of basal and luminal cells. Prostate cancer can be initiated in both benign stem cells, but because cell markers are not expressed patient tumors, the former result was unexpected. Since cells origin prostate important therapeutic targets, we sought to provide further proof that have tumorigenic potential. Prostatic were enriched based on α2β1integrin(hi) expression for using CD133 nontumorigenic BPH-1 Human embryonic (hESCs) also used as a source...
Background While it has been challenging to establish prostate cancer patient‐derived xenografts (PDXs), with a take rate of 10‐40% and long latency time, multiple groups throughout the world have developed methods for successful establishment serially transplantable human PDXs using variety immune deficient mice. In 2014, Movember Foundation launched Global Action Plan 1 (GAP1) project support an international collaborative PDX program involving eleven groups. Between these consortium...
// Damien A. Leach 1 , Eleanor F. Need Roxanne Toivanen 2 Andrew P. Trotta Helen M. Palenthorpe David J. Tamblyn 3 Tina Kopsaftis Georgina England 4 Eric Smith Paul Drew 1,5 Carole B. Pinnock Peng Lee 6 Jeff Holst 7,8 Gail Risbridger Samarth Chopra 3,9 Donald DeFranco 10 Renea Taylor 2,11 and Grant Buchanan The Basil Hetzel Institute for Translational Health Research, University of Adelaide, SA, Australia Department Anatomy Development, Monash University, VIC, Urology Unit, Repatriation...
Abstract The timing of puberty is highly variable and associated with long-term health outcomes. To date, understanding the genetic control based largely on studies in women. Here, we report a multi-trait genome-wide association study for male an effective sample size 205,354 men. We find moderately strong genomic correlation between sexes (rg = 0.68) identify 76 independent signals timing. Implicated mechanisms include unexpected link natural hair colour, possibly reflecting common effects...
Abstract Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish significant resource of patient-derived xenografts (PDXs) prostate for rapid and systematic evaluation candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012–2020, coinciding with availability abiraterone enzalutamide. PDXs represent the clinico-pathological genomic spectrum cancer, treatment-naïve primary castration-resistant metastases. Inter-...
New treatments are required for advanced prostate cancer; however, there fewer preclinical models of cancer than other common tumor types to test candidate therapeutics. One opportunity increase the scope studies is grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline automated seeding, treatment and an analysis drug responses organoids. We established cultures 5 PDXs with diverse phenotypes cancer, including castrate-sensitive...
Potent therapeutic inhibition of the androgen receptor (AR) in prostate adenocarcinoma can lead to emergence neuroendocrine cancer (NEPC), a phenomenon associated with enhanced cell plasticity. Here, we show that microRNA-194 (miR-194) is regulator epithelial-neuroendocrine transdifferentiation. In clinical samples, miR-194 expression and activity were elevated NEPC inversely correlated AR signaling. facilitated features cells, process mediated by its ability directly target suite genes...
Chimeric antigen receptor (CAR) T cells have transformed the treatment landscape for hematological malignancies. However, CAR are less efficient against solid tumors, largely due to poor infiltration resulting from immunosuppressive nature of tumor microenvironment (TME). Here, we assessed efficacy Lewis Y (LeY)-specific in patient-derived xenograft (PDX) models prostate cancer. In vitro, LeY directly killed organoids derived androgen (AR)-positive or AR-null PDXs. vivo, although alone did...
Abstract FOXA family proteins act as pioneer factors by remodeling compact chromatin structures. FOXA1 is crucial for the binding of androgen receptor (AR) in both normal prostate epithelial cells and luminal subtype cancer (PCa). Recent studies have highlighted emergence FOXA2 an adaptive response to AR signaling inhibition treatments. However, role transition regulating lineage plasticity remains unclear. Our study demonstrates that binds distinct classes developmental enhancers multiple...