A5084525017- Melanoma and MAPK Pathways
- Autophagy in Disease and Therapy
- Cell Adhesion Molecules Research
- Endoplasmic Reticulum Stress and Disease
- Cutaneous Melanoma Detection and Management
- Writing and Handwriting Education
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- Cellular Mechanics and Interactions
- Education and Technology Integration
- RNA regulation and disease
- 3D Printing in Biomedical Research
- Reading and Literacy Development
- Cancer Research and Treatments
- Cognitive and developmental aspects of mathematical skills
- Computational Drug Discovery Methods
- Immunotherapy and Immune Responses
- Cancer Cells and Metastasis
- Nanoplatforms for cancer theranostics
- Viral Infectious Diseases and Gene Expression in Insects
- Cell Image Analysis Techniques
- Cancer, Hypoxia, and Metabolism
- Traffic and Road Safety
- Disability Education and Employment
- Educational Assessment and Improvement
University of Sunderland
2020-2025
Newcastle University
2010-2021
Centenary Institute
2014-2021
The University of Sydney
2014-2020
Canadian Sport Centre Pacific
2019
Amgen (United States)
2017
McMaster University
2015
The Ohio State University
1979-2014
Weatherford College
2013
Cellular Therapeutics (United Kingdom)
2009
Abstract Exploiting vulnerabilities in the intracellular signaling pathways of tumor cells is a key strategy for development new drugs. The activation cellular stress responses mediated by endoplasmic reticulum (ER) allows cancer to survive outside their normal environment. Many proteins that protect against ER are active as protein disulfide isomerases (PDI) and aim this study was test hypothesis apoptosis response can be increased inhibiting PDI activity. We show novel chemotherapeutic...
Solid cancers are composed of heterogeneous zones containing proliferating and quiescent cells. Despite considerable insight into the molecular mechanisms underlying aberrant cell cycle progression, there is limited understanding relationship between on one side, melanoma motility, invasion, drug sensitivity other side. Utilizing fluorescent ubiquitination-based indicator (FUCCI) to longitudinally monitor proliferation migration cells in 3D culture vivo, we found that invading actively,...
Endoplasmic reticulum (ER) malfunction, leading to ER stress, can be a consequence of genome instability and hypoxic tissue environments. Cancer cells survive by acquiring or enhancing survival mechanisms counter the effects stress these homeostatic responses may new therapeutic targets. Understanding links between apoptosis approached using drugs specifically target in cancer cells. The retinoid analogue fenretinide [N-(4-hydroxyphenyl) retinamide] is preventive chemotherapeutic drug, that...
Metastatic melanoma remains incurable, emphasizing the acute need for improved research models to investigate underlying biologic mechanisms mediating tumor invasion and metastasis, develop more effective targeted therapies improve clinical outcome. Available animal of do not accurately reflect human disease current in vitro skin equivalent incorporating cells are fully representative microenvironment. We have developed a robust reproducible, humanized three-dimensional (3D) comprising...
Abstract Purpose: Metastatic melanoma is characterized by extremely poor survival rates and hence novel therapies are urgently required. The ability of many anticancer drugs to activate autophagy, a lysosomal-mediated catabolic process which usually promotes cell survival, suggests targeting the autophagy pathway may be means augment therapy. Experimental Design: Autophagy apoptosis were assessed in vitro human lines response clinically achievable concentrations endoplasmic reticulum (ER)...
Summary Melanoma drug resistance is often attributed to abrogation of the intrinsic apoptosis pathway. Targeting regulators thus considered a promising approach sensitizing melanomas treatment. The development small‐molecule inhibitors that mimic natural antagonists either antiapoptotic members BCL‐2 family or inhibitor proteins (IAPs), known as BH3‐ SMAC‐mimetics, respectively, are helping us understand mechanisms behind apoptotic resistance. Studies using BH3‐mimetics indicate protein...
Abstract Purpose: Single-agent chemotherapy is largely the treatment of choice for systemic therapy metastatic melanoma, but survival rates are low, and novel adjuvant therapies urgently required. Endoplasmic reticulum (ER) stress a potential therapeutic target, two relatively new drugs, fenretinide bortezomib (Velcade), each acting via different cellular mechanisms, induce ER leading to apoptosis in melanoma cells. The aim this study was test hypothesis that cells may be increased by...
<ns5:p>Cancer metastasis is the most important prognostic factor determining patient survival, but currently there are very few drugs or therapies that specifically inhibit invasion and of cancer cells. Currently, human largely studied using transgenic immunocompromised mouse xenograft models, which useful for analysing end-point tumour growth unable to accurately reliably monitor <ns5:italic>in vivo</ns5:italic> invasion, intravasation, extravasation secondary formation Furthermore, limits...
Doxorubicin (DOX), a potent chemotherapeutic, is commonly prescribed treatment for breast cancer, but limited by severe organ toxicity. Therefore, more effective therapies are required. This study developed novel DOX-liposomes (LipDOX-ALA-AA) co-loaded with alpha-lipoic-acid (ALA) and ascorbic-acid (AA) to enhance antineoplastic effect. Liposomes were fabricated using microfluidic-system DSPClipid:Cholesterol ratio of 1:1 flow rate 5:1. investigated various-techniques such-as dynamic light...
Targeting endoplasmic reticulum stress-induced apoptosis may offer an alternative therapeutic strategy for metastatic melanoma. Fenretinide and bortezomib induce of melanoma cells but their efficacy be hindered by the unfolded protein response, which promotes survival ameliorating stress. The aim this study was to test hypothesis that inhibition GRP78, a vital response mediator, increases cell death in combination with stress-inducing agents. Down-regulation GRP78 small-interfering RNA...
Abstract The B cl‐2 family member M cl‐1 is essential for melanoma survival; however, the influence of oncogenic BRAF signalling remains elusive. In this study, splice variant expression was determined in a panel cell lines relation to mutational status. L m RNA increased cells compared with primary melanocytes significantly and protein observed V600E mutant cells. Although no change cl‐1S observed, S also Additionally, while over‐expression both expression, inhibition hyperactive resulted...
Patients with malignant melanoma often relapse after treatment BRAF and/or mitogen‐activated protein kinase (MEK) inhibitors (MEKi) owing to development of drug resistance. To establish the temporal pattern CD271 regulation during resistance by trametinib, and determine association between trametinib induction prosurvival autophagy. Immunohistochemistry for p62 was performed on human naevi primary tumours. Western blotting used analyse expression CD271, LC3 in subpopulations. Flow cytometry...
Presently, there are numerous structural classes of cannabinoid receptor agonists, all which require solubilization for experimental purposes. One strategy solubilizing water-insoluble tetrahydrocannabinols is conversion the phenolic hydroxyl to a morpholinobutyryloxy substituent. The hydrochloride salts these analogs water-soluble and active in vivo when administered saline. present investigation demonstrated that substituted butyryloxy esters highly potent. substitutions include...
<ns4:p>Cancer metastasis is the most important prognostic factor determining patient survival, but currently there are very few drugs or therapies that specifically inhibit invasion and of cancer cells. Currently, human largely studied using transgenic immunocompromised mouse xenograft models, which useful for analysing end-point tumour growth unable to accurately reliably monitor <ns4:italic>in vivo</ns4:italic> invasion, intravasation, extravasation secondary formation Furthermore, limits...
Abstract Phenotypic heterogeneity of cancer cells plays a critical role in shaping treatment response. This type is organized spatially with specific phenotypes, such as sharply demarcated clusters proliferating and cell cycle-arrested cells, predominating within discrete domains tumor. What determines the occurrence tumor phenotypes distinct microdomains solid cancers poorly understood. Here, we show that melanoma spatial organization phenotypic dictated by expression activity MITF. We...
AbstractA comparison was made of the accuracy transitional cursive letter strokes on large-spaced paper and normal-spaced second third grade students. Results indicate that both students produce more accurate with (space size 1.11 cm). Third graders produced significantly correct than graders. These data revealed no significant differences between formation girls boys. The results support continued use writing letters.
For patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of autophagy regulatory protein AMBRA1 and terminal differentiation marker loricrin in peritumoral epidermis is associated a significantly increased risk metastasis.
ABSTRACT Retinoic acid (RA) exerts a variety of effects on the regenerating urodele limb including positional respecification blastema. The major RA receptor expressed in newt and blastema is 1 isoform and, order to detect this context, we have made five affinity-purified antibodies against fusion proteins peptides from non-overlapping regions molecule. These been evaluated by reaction with transfected COS-7 cells, cells culture tissue sections. most informative were RP6, directed N-terminal...