A5082911781- Thyroid Cancer Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cell Adhesion Molecules Research
- Cancer-related Molecular Pathways
- Thyroid Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Pituitary Gland Disorders and Treatments
- Cancer, Lipids, and Metabolism
- TGF-β signaling in diseases
- Prostate Cancer Treatment and Research
- RNA modifications and cancer
- Neonatal Respiratory Health Research
- Ubiquitin and proteasome pathways
- Radiopharmaceutical Chemistry and Applications
- Cancer Immunotherapy and Biomarkers
- Hormonal and reproductive studies
- Amino Acid Enzymes and Metabolism
- Immunotherapy and Immune Responses
- Inflammatory mediators and NSAID effects
- Genetic factors in colorectal cancer
- Estrogen and related hormone effects
- Nutrition, Genetics, and Disease
- Cancer-related gene regulation
- Glutathione Transferases and Polymorphisms
- Semantic Web and Ontologies
University of California, San Francisco
2014-2024
University of Birmingham
2010-2023
University of York
2017-2019
Yorkshire Cancer Research
2017-2019
University Hospitals Birmingham NHS Foundation Trust
2011
University of Ferrara
2011
Memorial Sloan Kettering Cancer Center
2011
TGF-β is a promising immunotherapeutic target. It expressed ubiquitously in latent form that must be activated to function. Determination of where and how (L-TGF-β) the tumor microenvironment could facilitate cell- mechanism-specific approaches immunotherapeutically target TGF-β. Binding L-TGF-β integrin αvβ8 results activation We engineered used antibodies optimized for blocking or detection, which — respectively inhibit growth syngeneic models sensitively specifically detect β8 human...
Therapeutic targeting of an extended-closed conformation the integrin αvβ8 inhibits TGF-β activation and ameliorates symptoms experimental airway disease in mice.
Abstract Interleukin-4 plays a critical role in the regulation of immune responses and has been detected at high levels tumour microenvironment cancer patients, where concentrations correlate with grade malignancy. In prostate cancer, interleukin-4 associated activation androgen receptor, increased proliferation survival pathways such as Akt NF-κB. However, its therapy resistance not yet determined. Here we investigate influence on primary epithelial cells from patients. Our data demonstrate...
TGF-β, essential for development and immunity, is expressed as a latent complex (L-TGF-β) non-covalently associated with its prodomain presented on immune cell surfaces by covalent association GARP. Binding to integrin αvβ8 activates L-TGF-β1/GARP. The dogma that mature TGF-β must physically dissociate from L-TGF-β1 signaling occur. Our previous studies discovered αvβ8-mediated autocrine can occur without TGF-β1 release form. Here, we show mice engineered express cannot survive early lethal...
Abstract Pituitary tumor transforming gene (PTTG)-binding factor (PBF or PTTG1IP) is a little characterized proto-oncogene that has been implicated in the etiology of breast and thyroid tumors. In this study, we created murine transgenic model to target PBF expression gland (PBF-Tg mice) found these mice exhibited normal function, but striking enlargement associated with hyperplastic macrofollicular lesions. Expression sodium iodide symporter (NIS), essential radioiodine ablation...
The PTTG1-binding factor (PBF/PTTG1IP) has an emerging repertoire of roles, especially in thyroid biology, and functions as a protooncogene. High PBF expression is independently associated with poor prognosis lower disease-specific survival human cancer. However, the precise role tumorigenesis unclear. Here, we present extensive evidence demonstrating that novel regulator p53, tumor suppressor protein key maintaining genetic stability, which infrequently mutated differentiated By...
Alveolar formation requires coordinated movement and interaction between alveolar epithelial cells, mesenchymal myofibroblasts, endothelial cells/pericytes to produce secondary septa. These processes rely on the acquisition of distinct cellular properties enable ligand secretion for cell-cell signaling initiate morphogenesis through contraction, cell migration, shape change. In this study, we showed that mitochondrial activity distribution play a key role in bestowing functions both cells...
ABSTRACT The ability of adenovirus early region proteins, E1B-55K and E4orf6, to usurp control cellular ubiquitin ligases target proteins for proteasome-dependent degradation during infection is well established. Here we show that the E4 gene product, E4orf3 can, independently transcriptional corepressor intermediary factor 1γ (TIF1γ) proteasome-mediated infection. Initial mass spectrometric studies identified TIF1 family members—TIF1α, TIF1β, TIF1γ—as E1B-55K-binding in both transformed...
Tumor cells expressing integrin αvβ8 activated latent TGF-β on T cells, inducing reg enrichment and tumor immunosuppression.
Macrophages are paracrine signalers that regulate tissular responses to injury through interactions with parenchymal cells. Connexin hemichannels have recently been shown mediate efflux of ATP by macrophages, resulting cytosolic calcium in adjacent Here we report lung macrophages deletion connexin 43 (MacΔCx43) had decreased into the extracellular space and induced a response co-cultured fibroblasts compared WT macrophages. Furthermore, MacΔCx43 mice fibrosis after bleomycin-induced injury....
The PTTG1-binding factor (PBF) is a transforming gene capable of eliciting tumor formation in xenograft models. However, the precise role PBF tumorigenesis and its prognostic value as cancer biomarker remain largely uncharacterised, particularly malignancies outside thyroid. Here, we provide first evidence that represents promising marker colorectal cancer. Examination total 39 patients demonstrated higher expression at both mRNA (P = 0.009) protein < 0.0001) level tumors compared to matched...
Prostate cancer research is hampered by the lack of in vivo preclinical models that accurately reflect patient tumour biology and clinical heterogeneity human prostate cancer. To overcome these limitations we propagated characterised a new collection patient-derived xenografts. Tumour fragments from 147 unsupervised, surgical samples were implanted subcutaneously into immunodeficient Rag2-/-γC-/- mice within 24 hours surgery. Histologic molecular characterisation xenografts was compared with...
Within the basolateral membrane of thyroid follicular epithelial cells, two transporter proteins are central to hormone (TH) biosynthesis and secretion. The sodium iodide symporter (NIS) delivers from bloodstream into thyroid, after TH biosynthesis, monocarboxylate 8 (MCT8) mediates secretion gland. Pituitary tumor-transforming gene-binding factor (PBF; PTTG1IP) is a protooncogene that up-regulated in cancer binds NIS modulates its subcellular localization function. We now show PBF MCT8...
Abstract Loss of latexin (LXN) expression negatively correlates with the prognosis several human cancers. Despite association numerous processes including haematopoietic stem cell (HSC) fate, inflammation and tumour suppression, a clearly defined biological role for LXN is still lacking. Therefore, we sought to understand function in normal malignant prostate assess its potential as therapeutic target. Our data demonstrate that highly expressed luminal cells but downregulated high Gleason...
Antiandrogen therapy is a primary treatment for patients with metastasized prostate cancer. Whilst the biologic mechanisms of antiandrogens have been extensively studied, operating protocols used characterization these drugs were not identical, limiting their comparison. Here, Bicalutamide, Enzalutamide, Apalutamide, and Darolutamide systematically compared using identical experimental setups. Androgen-dependent LNCaP LAPC4 cells as well androgen-independent C4-2 treated distinct...
Human pituitary tumor transforming gene (hPTTG) is a multifunctional proto-oncogene implicated in the initiation and progression of several tumors. Phosphorylation hPTTG mediated by cyclin-dependent kinase 2 (CDC2), whereas cellular expression regulated specificity protein 1 (SP1). The mechanisms underlying propagation aberrant thyroid cell growth have not been fully defined. We set out to investigate interplay between factors, as well effects phosphorylation SP1 regulation on function. In...
The multifunctional cytokine TGF-b is produced in a latent form (L-TGF-b) where RGD containing homodimeric prodomain forms "ring" encircling mature TGF-b, shielding it from its receptors. Thus L-TGF-b must be activated to function, process driven by dynamic allostery resulting integrin binding the motif. Here we provide critical evidence that defines domain-swapped architecture of L-TGF-b, an essential component mechanism activation.
The multifunctional cytokine TGF-β is produced in a latent form (L-TGF-β) where RGD containing homodimeric prodomain forms ring encircling mature shielding it from its receptors. Thus L-TGF-β must be activated to function, process driven by dynamic allostery resulting integrin binding the motif. Here we provide critical evidence that defines domain-swapped architecture of L-TGF-β, an essential component mechanism activation.
Urothelial cancer (UC) is one of the most common cancers in Europe and also costliest to treat. When first line therapies show initial success, around 50% relapse proceed metastasis. In this study we assessed Protein inhibitor activated signal transducers activators transcription (PIAS)1 as a potential therapeutic target urothelial cancer. PIAS1 key regulator STAT1 signalling may be implicated carcinogenesis. contrast other types protein expression not significantly different malignant areas...
The Anjing Hitam sedex lead/zinc/silver deposit currently estimated to contain 10 million tonnes at approximately 25% Pb/Zn combined is one of the most significant new basemetal discoveries in world last ten years. still open its deeper southern extremity located Sopokomil Northern Sumatra , Indonesia some 250 kilometres SW from city Medan an area high mountainous relief and only recently recognised as having potential host deposits . In July 1999 two years after commencement exploration...
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)