A5010545255- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Mechanisms of cancer metastasis
- Cytokine Signaling Pathways and Interactions
- Hormonal and reproductive studies
- S100 Proteins and Annexins
- Breast Cancer Treatment Studies
- Computational Drug Discovery Methods
- Genomics and Chromatin Dynamics
- Hormonal Regulation and Hypertension
- Prostate Cancer Treatment and Research
- Inflammatory mediators and NSAID effects
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Lung Cancer Treatments and Mutations
- Retinoids in leukemia and cellular processes
- Cancer Genomics and Diagnostics
- Sexual Differentiation and Disorders
- Cancer, Lipids, and Metabolism
- Metabolism, Diabetes, and Cancer
- Melanoma and MAPK Pathways
- Cell Adhesion Molecules Research
- Cancer-related gene regulation
- Radiopharmaceutical Chemistry and Applications
Royal College of Surgeons in Ireland
2011-2024
University College Dublin
2010-2024
St. Vincent's University Hospital
2010-2024
University of Medicine and Health Sciences
2024
Beaumont Hospital
2013-2018
Baylor College of Medicine
2011-2014
University of Ulster
2005-2008
Nokia (United States)
1982
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Genome-wide screen identifies methylation of the estrogen-repressed HOXC10 gene as a determinant resistance to aromatase inhibitors in breast cancer.
This study investigates the role of p160 coactivators AIB1 and SRC-1 independently, their interactions with estrogen receptor, in development resistance to endocrine treatments.The expression p160s interactions, was analyzed by immunohistochemistry quantitative coassociation immunofluorescent microscopy, using cell lines, primary breast tumor cultures, a tissue microarray cancer samples from 560 patients.Coassociation receptor alpha increased LY2 endocrine-resistant line following treatment...
Abstract Mechanisms of acquired resistance to endocrine therapy in breast cancer, a major clinical challenge, are poorly understood. We have used mass spectrometry–based screen identify proteins that associated with the endocrine-resistant phenotype. In this study, we report identification novel pathway involving interactions developmental transcription HOXC11 steroid receptor coactivator protein SRC-1, which is strong predictor reduced disease-free survival cancer patients. and SRC-1...
The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity that permits the emergence a hormone-independent tumor. steroid coactivator protein SRC-1, through interactions with developmental proteins and other nonsteroidal transcription factors, drives this tumor adaptability. In discovery study, we identified ADAM22, non-protease member ADAM family disintegrins, as direct estrogen receptor (ER)-independent target SRC-1. We confirmed SRC-1...
The use of aromatase inhibitors (AI) in the treatment estrogen receptor (ER)-positive, postmenopausal breast cancer has proven efficacy. However, inappropriate activation ER target genes been implicated development resistant tumors. coactivator protein AIB1 previously associated with initiation and resistance to endocrine therapy.Here, we investigated role deregulation occurring as a consequence AI using tissue microarrays patients cell line models letrozole.Expression disease recurrence (P...
Transcriptional control is the major determinant of cell fate. The steroid receptor coactivator (SRC)-1 enhances activity estrogen in breast cancer cells, where it confers survival benefits. Here, we report that a global analysis SRC-1 target genes suggested also mediates transcriptional repression cells. Combined and HOXC11 ChIPseq identified differentiation marker, CD24, apoptotic protein, PAWR, as direct SRC-1/HOXC11 suppression targets. Reduced expression both CD24 PAWR was associated...
Disease recurrence is a common problem in breast cancer and yet the mechanisms enabling tumor cells to evade therapy colonize distant organs remain unclear. We sought characterize global expression changes occurring with metastatic disease progression endocrine-resistant setting.Here, for first time, RNAsequencing has been performed on matched primary, nodal, liver tumors from tamoxifen-treated patients following progression. Expression of genes commonly elevated metastases sequenced was...
Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How mediates its effects the consequence of it on clinical outcome has not been fully elucidated. The participation coregulatory proteins modulating receptor (ER) function input crosstalk with tyrosine kinase HER2 was investigated. Oestrogen induced cell proliferation follicular cancer (FTC)-133 cells, but anaplastic 8305C line. Knockdown coactivator steroid (SRC)-1 inhibited FTC-133 basal,...
Cyclooxygenase-2 (COX-2) is associated with breast tumour progression. Clinical and molecular studies implicate human epidermal growth factor receptor 2 (HER2) in the regulation of COX-2 expression. Recent reports raise possibility that HER2 could mediate these effects through direct transcriptional mechanisms. The relationship between was investigated a cohort cancer patients or without endocrine treatment. A tissue microarray comprising tumours from 560 10-year follow-up analysed for HER2,...
Human cancers utilise telomerase to maintain telomeres and prohibit cell senescence. reverse transcriptase (hTERT), an essential component of this complex, is regulated at the level gene transcription. Using SILAC‐proteomic analysis molecular studies, we identified AAA+ ATPase, RuvBl2 as a transcriptional regulator hTERT established that regulation through cooperation with Ets‐2. In colon cancer patients, nuclear expression associated hTERT, pEts2 advanced nodal disease ( P < 0.01, = 0.05...
Endocrine therapy is standard treatment for estrogen receptor (ER)-positive breast cancer. However, its efficacy limited by intrinsic and acquired resistance. Here the potential of S100β as a biomarker inhibition signaling network therapeutic strategy in endocrine treated patients was investigated. The expression tissue serum assessed immunohistochemistry an enzyme-linked immunosorbent assay, respectively. investigated cell line models resistance western blot, PCR, immunoprecipitation,...
Cutaneous melanoma is an aggressive disease. S100beta established biomarker of disease progression; however, the mechanism its regulation in undefined.Expression HOXC11 and SRC-1 was examined by immunohistochemistry immunofluorescence. Molecular cellular techniques were used to investigate S100beta, including, western blot, qPCR, ChIP migration assays.Expression levels transcription factor coactivator significantly elevated malignant comparison with benign nevi (P<0.001 P=0.017,...
Pericytes, located in close proximity to the underlying endothelium, form an integral component of microvasculature. These cells are intimately involved angiogenesis, which is fundamental importance many physiological and pathological processes. We evaluated influence pericyte-conditioned medium (PCM) on endothelial cell growth characteristics modulation gene expression.Migration tubule formation assays were performed vitro determine effect PCM characteristics. cDNA microarray analysis was...
Divergent roles for androgen receptor (AR) in breast cancer have been reported. Following aromatase inhibitor (AI) treatment, the conversion of circulating androgens into estrogens can be diminished by >99%. We wished to establish whether steroid environment dictate role AR and implications this subsequent therapy. This study utilizes models AI resistance explore responsiveness PI3K/mTOR anti-AR therapy when cells are exposed unconverted weak androgens. Transcriptomic alterations driven...
Abstract Context 11-Oxygenated androgens are a group of adrenal-derived steroids that require peripheral activation. In vitro data highlight putative role for 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) in 11-oxygenated androgen biosynthesis, converting 11β-hydroxyandrostenedione to 11-ketoandrostenedione (11KA4), the direct precursor potent 11-ketotestosterone (11KT). As kidney is major site HSD11B2 expression, we hypothesized patients with chronic disease (CKD) would have reduced...