A5053097935- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Radiopharmaceutical Chemistry and Applications
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Peptidase Inhibition and Analysis
- Cancer Immunotherapy and Biomarkers
- Hormonal and reproductive studies
- Circular RNAs in diseases
- Prostate Cancer Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Cancer, Lipids, and Metabolism
- Cancer-related gene regulation
- Mass Spectrometry Techniques and Applications
- Lung Cancer Research Studies
- Cancer Cells and Metastasis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Advanced Breast Cancer Therapies
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Heat shock proteins research
- Immune cells in cancer
- Esophageal Cancer Research and Treatment
- Angiogenesis and VEGF in Cancer
Imperial College London
2016-2025
Hammersmith Hospital
2016-2024
Prostate Cancer Research
2024
The London College
2021-2023
Massachusetts Department of Public Health
2022
Queen Elizabeth Hospital
2015-2018
Basil Hetzel Institute
2013-2018
The University of Adelaide
2013-2018
Centre for Cancer Biology
2017
Freemasons Foundation Centre for Men's Health
2013
Protocadherin 19 (PCDH19) female limited epilepsy (PCDH19-FE; also known as and mental retardation to females, EFMR; MIM300088) is an infantile onset syndrome with or without intellectual disability (ID) autism. We investigated transcriptomes of PCDH19-FE control primary skin fibroblasts, which are endowed metabolize neurosteroid hormones. identified a set 94 significantly dysregulated genes in females. Intriguingly, 43 the (45.7%) showed gender-biased expression; enrichment such was highly...
Abstract SARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 TMPRSS2. Downregulation of one or both these is thus a potential therapeutic approach for COVID-19. TMPRSS2 known target androgen receptor, ligand-activated transcription factor; receptor activation increases levels in tissues, notably prostate. We show here that treatment with antiandrogen enzalutamide—a well-tolerated drug widely used advanced prostate...
Emerging evidence indicates that metabolic dysregulation drives prostate cancer (PCa) progression and metastasis. AMP-activated protein kinase (AMPK) is a master regulator of metabolism, although its role in PCa remains unclear. Here, we show genetic pharmacological activation AMPK provides protective effect on vivo. We induces PGC1α expression, leading to catabolic reprogramming cells. This state characterized by increased mitochondrial gene fatty acid oxidation, decreased lipogenic...
Cancer genome sequencing has implicated the cytosine deaminase activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) genes as an important source mutations in diverse cancers, with APOBEC3B (A3B) expression especially correlated such cancer mutations. To better understand processes directing A3B over-expression cancer, and possible therapeutic avenues for targeting A3B, we have investigated regulation gene expression. Here, show that is inversely related to p53...
// 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...
Androgen receptor (AR) signalling is a key prostate cancer (PC) driver, even in advanced 'castrate-resistant' disease (CRPC). To systematically identify microRNAs (miRs) modulating AR activity lethal disease, hormone-responsive and -resistant PC cells expressing luciferase-based reporter were transfected with miR inhibitor library; 78 inhibitors significantly altered activity. Upon validation, miR-346, miR-361-3p miR-197 markedly reduced transcriptional activity, mRNA protein levels,...
Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, well known for their antimicrobial activity, released in high quantities by infiltrating immune cells breast cancer. However, the functional importance of presence within tumour microenvironment is unclear. We have recently described a new role peroxidases as key regulators fibroblast endothelial cell functionality. In present study, we investigate first time, ability to promote cancer development progression....
Abstract Background Current strategies to inhibit androgen receptor (AR) are circumvented in castration-resistant prostate cancer (CRPC). Cyclin-dependent kinase 7 (CDK7) promotes AR signalling, addition established roles cell cycle and global transcription, providing a rationale for its therapeutic targeting CRPC. Methods The antitumour activity of CT7001, an orally bioavailable CDK7 inhibitor, was investigated across CRPC models vitro xenograft vivo. Cell-based assays transcriptomic...
Prostate cancer (PCa) is a highly prevalent disease, causing the second largest amount of male deaths worldwide. Currently, prostate specific antigen (PSA) blood test remains standard serum prognostic and diagnostic monitoring biomarker but it lacks specificity sensitivity. PSA testing can lead to invasive biopsies which result in under detection clinically significant disease potential overtreatment indolent disease. There are promising circulating biomarkers could facilitate less more...
Prostate cancer (PCa) is an androgen receptor (AR) driven, high-incidence disease significantly contributing to mortality. PCa in need of better risk stratification at diagnosis and treatment outcomes patients high metastasis. The unfolded protein response (UPR) AR-dependent process. However, the impact UPR transducer IRE1 on biology resistance has not been defined. We use diverse pre-clinical models stress describe activity multiple stages demonstrate its involvement with poor prognosis...
Prostate cancer (PCa) is a highly prevalent disease, causing the second largest amount of male deaths worldwide. Currently, prostate specific antigen (PSA) test remains standard serum prognostic and diagnostic monitoring biomarker but it lacks specificity sensitivity. PSA testing can lead to invasive biopsies which result in under detection clinically significant disease potential overtreatment indolent disease. Promising circulating biomarkers could facilitate less more accurate tests,...
In breast cancer, progesterone receptor (PR) positivity or abundance is positively associated with survival and treatment response. It was initially believed that PR a useful diagnostic marker of estrogen activity, but increasingly has been recognised to play an important biological role in homeostasis, carcinogenesis metastasis. Although expression almost exclusively observed positive tumors, few studies have investigated the cellular mechanisms action context ongoing signalling. this...
In prostate cancer (PCa), and many other hormone-dependent cancers, there is clear evidence for distorted transcriptional control as disease driver mechanisms. Defining which transcription factor (TF) coregulators are altered combine to become oncogenic drivers remains a challenge, in part because of the multitude TFs diverse genomic space on they function. The current study was undertaken identify commonly PCa. We generated unique lists (n = 2662), coactivators (COA; n 766); corepressors...
Abstract Background miR-346 was identified as an activator of Androgen Receptor (AR) signalling that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). We sought to delineate the impact on damage, and its potential a therapeutic agent. Methods RNA-IP, RNA-seq, RNA-ISH, fibre assays, vivo xenograft studies bioinformatics approaches were used alongside novel method for amplification-free, single nucleotide-resolution genome-wide mapping breaks (INDUCE-seq)....
Solid tumors have an increased reliance on Hsp70/Hsp90 molecular chaperones for proliferation, survival and maintenance of intracellular signaling systems. An underinvestigated component the chaperone system is tetratricopeptide repeat (TPR)-containing cochaperone, which coordinates involvement client proteins as well having diverse individual actions. A potentially important cochaperone in prostate cancer (PCa) small glutamine-rich TPR-containing protein alpha (SGTA), interacts with...
Patients with prostate cancer treated androgen deprivation therapy (ADT) eventually develop castrate-resistant (CRPC). 1,25-Dihydroxyvitamin D3 (1,25D3/calcitriol) is a potential adjuvant that confers antiproliferative and pro-differentiation effects in vitro, but has had mixed results clinical trials. The impact of the tumor microenvironment on 1,25D3 patients CRPC not been assessed. Transforming growth factor β (TGFβ), which associated development tumorigenic "reactive stroma" cancer,...
Breast cancer (BC) is the most diagnosed in women worldwide. In estrogen receptor (ER)-positive disease, anti-estrogens and aromatase inhibitors (AI) improve patient survival; however, many patients develop resistance. Dysregulation of apoptosis a common resistance mechanism; thus, agents that can reinstate activity apoptotic pathways represent promising therapeutics for advanced drug-resistant disease. Emerging targets this scenario include microRNAs (miRs). To identify miRs modulating...