Search

Your search keyword '"Clarkson, Richard W"' showing total 131 results
Start Over Author "Clarkson, Richard W"
131 results on '"Clarkson, Richard W"'

1. Development and Characterisation of a New Patient-Derived Xenograft Model of AR-Negative Metastatic Castration-Resistant Prostate Cancer

Author

Turnham, Daniel J., primary, Mullen, Manisha S., additional, Bullock, Nicholas P., additional, Gilroy, Kathryn L., additional, Richards, Anna E., additional, Patel, Radhika, additional, Quintela, Marcos, additional, Meniel, Valerie S., additional, Seaton, Gillian, additional, Kynaston, Howard, additional, Clarkson, Richard W. E., additional, Phesse, Toby J., additional, Nelson, Peter S., additional, Haffner, Michael C., additional, Staffurth, John N., additional, and Pearson, Helen B., additional

Published
2024
Full Text
View/download PDF

3. Supplemetary Material and Tables from Identification of Pik3ca Mutation as a Genetic Driver of Prostate Cancer That Cooperates with Pten Loss to Accelerate Progression and Castration-Resistant Growth

Author

Pearson, Helen B., primary, Li, Jason, primary, Meniel, Valerie S., primary, Fennell, Christina M., primary, Waring, Paul, primary, Montgomery, Karen G., primary, Rebello, Richard J., primary, Macpherson, Arthi A., primary, Koushyar, Sarah, primary, Furic, Luc, primary, Cullinane, Carleen, primary, Clarkson, Richard W., primary, Smalley, Matthew J., primary, Simpson, Kaylene J., primary, Phesse, Toby J., primary, Shepherd, Peter R., primary, Humbert, Patrick O., primary, Sansom, Owen J., primary, and Phillips, Wayne A., primary

Published
2023
Full Text
View/download PDF

4. Data from Identification of Pik3ca Mutation as a Genetic Driver of Prostate Cancer That Cooperates with Pten Loss to Accelerate Progression and Castration-Resistant Growth

Author

Pearson, Helen B., primary, Li, Jason, primary, Meniel, Valerie S., primary, Fennell, Christina M., primary, Waring, Paul, primary, Montgomery, Karen G., primary, Rebello, Richard J., primary, Macpherson, Arthi A., primary, Koushyar, Sarah, primary, Furic, Luc, primary, Cullinane, Carleen, primary, Clarkson, Richard W., primary, Smalley, Matthew J., primary, Simpson, Kaylene J., primary, Phesse, Toby J., primary, Shepherd, Peter R., primary, Humbert, Patrick O., primary, Sansom, Owen J., primary, and Phillips, Wayne A., primary

Published
2023
Full Text
View/download PDF

5. Figure S2 from Identification of Pik3ca Mutation as a Genetic Driver of Prostate Cancer That Cooperates with Pten Loss to Accelerate Progression and Castration-Resistant Growth

Author

Pearson, Helen B., primary, Li, Jason, primary, Meniel, Valerie S., primary, Fennell, Christina M., primary, Waring, Paul, primary, Montgomery, Karen G., primary, Rebello, Richard J., primary, Macpherson, Arthi A., primary, Koushyar, Sarah, primary, Furic, Luc, primary, Cullinane, Carleen, primary, Clarkson, Richard W., primary, Smalley, Matthew J., primary, Simpson, Kaylene J., primary, Phesse, Toby J., primary, Shepherd, Peter R., primary, Humbert, Patrick O., primary, Sansom, Owen J., primary, and Phillips, Wayne A., primary

Published
2023
Full Text
View/download PDF

24. Synergistic targeting of breast cancer stem-like cells by human γδ T cells and CD8+ T cells

Author

Chen, Hung-Chang, Joalland, Noémie, Bridgeman, John S, Alchami, Fouad S, Jarry, Ulrich, Khan, Mohd Wajid A, Piggott, Luke, Shanneik, Yasmin, Li, Jianqiang, Herold, Marco J, Herrmann, Thomas, Price, David A, Gallimore, Awen M, Clarkson, Richard W, Scotet, Emmanuel, Moser, Bernhard, Eberl, Matthias, Division of Infection and Immunity [Cardiff, UK] (School of Medicine), Cardiff University, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Cardiff and Vale University Health Board [Cardiff, UK], University Hospital of Wales [Cardiff, UK], School of Biosciences [Cardiff], Institute for Virology and Immunobiology [Würzburg, Germany], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), The Walter and Eliza Hall Institute of Medical Research (WEHI), Systems Immunity Research Institute [Cardiff, UK], European Cancer Stem Cell Research Institute [Cardiff, UK], Bernardo, Elizabeth, University Hospital of Wales (UHW), and Julius-Maximilians-Universität Würzburg (JMU)

Subjects
Cytotoxicity, Immunologic, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, CD8-Positive T-Lymphocytes, Zoledronic Acid, Antibodies, Major Histocompatibility Complex, RC0254, Epitopes, Interferon-gamma, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Animals, Humans, Breast, Diphosphonates, Imidazoles, Epithelial Cells, Receptors, Antigen, T-Cell, gamma-delta, Immunity, Innate, Phenotype, ras Proteins, Neoplastic Stem Cells, Female, Original Article
Abstract

International audience; The inherent resistance of cancer stem cells (CSCs) to existing therapies has largely hampered the development of effective treatments for advanced malignancy. To help develop novel immunotherapy approaches that efficiently target CSCs, an experimental model allowing reliable distinction of CSCs and non-CSCs was set up to study their interaction with non-MHC-restricted γδ T cells and antigen-specific CD8 + T cells. Stable lines with characteristics of breast CSC-like cells were generated from ras-transformed human mammary epithelial (HMLER) cells as confirmed by their CD44 hi CD24 lo GD2 + phenotype, their mesenchymal morphology in culture and their capacity to form mammospheres under non-adherent conditions, as well as their potent tumorigenicity, self-renewal and differentiation in xenografted mice. The resistance of CSC-like cells to γδ T cells could be overcome by inhibition of farnesyl pyrophosphate synthase (FPPS) through pretreatment with zoledronate or with FPPS-targeting short hairpin RNA. γδ T cells induced upregulation of MHC class I and CD54/ICAM-1 on CSC-like cells and thereby increased the susceptibility to antigen-specific killing by CD8 + T cells. Alternatively, γδ T-cell responses could be specifically directed against CSC-like cells using the humanised anti-GD2 monoclonal antibody hu14.18K322A. Our findings identify a powerful synergism between MHC-restricted and non-MHC-restricted T cells in the eradication of cancer cells including breast CSCs. Our research suggests that novel immunotherapies may benefit from a two-pronged approach combining γδ T-cell and CD8 + T-cell targeting strategies that triggers effective innate-like and tumour-specific adaptive responses.

Published
2017
Full Text
View/download PDF

26. Identification of Pik3ca Mutation as a Genetic Driver of Prostate Cancer That Cooperates with Pten Loss to Accelerate Progression and Castration-Resistant Growth

Author

Pearson, Helen B., primary, Li, Jason, additional, Meniel, Valerie S., additional, Fennell, Christina M., additional, Waring, Paul, additional, Montgomery, Karen G., additional, Rebello, Richard J., additional, Macpherson, Arthi A., additional, Koushyar, Sarah, additional, Furic, Luc, additional, Cullinane, Carleen, additional, Clarkson, Richard W., additional, Smalley, Matthew J., additional, Simpson, Kaylene J., additional, Phesse, Toby J., additional, Shepherd, Peter R., additional, Humbert, Patrick O., additional, Sansom, Owen J., additional, and Phillips, Wayne A., additional

Published
2018
Full Text
View/download PDF

28. Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup

Author

Cowley, Michael, Garfield, Alastair S., Madon-Simon, Marta, Charalambous, Marika, Clarkson, Richard W., Smalley, Matthew J., Kendrick, Howard, Isles, Anthony R., Parry, Aled J., Carney, Sara, Oakey, Rebecca J., Heisler, Lora K., Moorwood, Kim, Wolf, Jason B., and Ward, Andrew

Subjects
Mice, Knockout, Genomic Imprinting, Lactation/genetics, Mice, STAT5 Transcription Factor/physiology, Receptors, Cytoplasmic and Nuclear/physiology, Karyopherins/physiology, GRB10 Adaptor Protein/genetics, Animals, Gene Expression Regulation, Developmental, Female, Body Size/genetics, R1
Abstract

Developmental programming links growth in early life with health status in adulthood. Although environmental factors such as maternal diet can influence the growth and adult health status of offspring, the genetic influences on this process are poorly understood. Using the mouse as a model, we identify the imprinted gene Grb10 as a mediator of nutrient supply and demand in the postnatal period. The combined actions of Grb10 expressed in the mother, controlling supply, and Grb10 expressed in the offspring, controlling demand, jointly regulate offspring growth. Furthermore, Grb10 determines the proportions of lean and fat tissue during development, thereby influencing energy homeostasis in the adult. Most strikingly, we show that the development of normal lean/fat proportions depends on the combined effects of Grb10 expressed in the mother, which has the greater effect on offspring adiposity, and Grb10 expressed in the offspring, which influences lean mass. These distinct functions of Grb10 in mother and pup act complementarily, which is consistent with a coadaptation model of imprinting evolution, a model predicted but for which there is limited experimental evidence. In addition, our findings identify Grb10 as a key genetic component of developmental programming, and highlight the need for a better understanding of mother-offspring interactions at the genetic level in predicting adult disease risk.

Published
2014
Full Text
View/download PDF

29. Synergistic targeting of breast cancer stem-like cells by human γδ T cells and CD8+ T cells.

Author

Chen, Hung‐Chang, Joalland, Noémie, Bridgeman, John S, Alchami, Fouad S, Jarry, Ulrich, Khan, Mohd Wajid A, Piggott, Luke, Shanneik, Yasmin, Li, Jianqiang, Herold, Marco J, Herrmann, Thomas, Price, David A, Gallimore, Awen M, Clarkson, Richard W, Scotet, Emmanuel, Moser, Bernhard, and Eberl, Matthias

Subjects
BREAST cancer treatment, CANCER cells, STEM cells, T cells, CD8 antigen, CANCER immunotherapy
Abstract

The inherent resistance of cancer stem cells (CSCs) to existing therapies has largely hampered the development of effective treatments for advanced malignancy. To help develop novel immunotherapy approaches that efficiently target CSCs, an experimental model allowing reliable distinction of CSCs and non-CSCs was set up to study their interaction with non-MHC-restricted γδ T cells and antigen-specific CD8+ T cells. Stable lines with characteristics of breast CSC-like cells were generated from ras-transformed human mammary epithelial (HMLER) cells as confirmed by their CD44hi CD24lo GD2+ phenotype, their mesenchymal morphology in culture and their capacity to form mammospheres under non-adherent conditions, as well as their potent tumorigenicity, self-renewal and differentiation in xenografted mice. The resistance of CSC-like cells to γδ T cells could be overcome by inhibition of farnesyl pyrophosphate synthase (FPPS) through pretreatment with zoledronate or with FPPS-targeting short hairpin RNA. γδ T cells induced upregulation of MHC class I and CD54/ICAM-1 on CSC-like cells and thereby increased the susceptibility to antigen-specific killing by CD8+ T cells. Alternatively, γδ T-cell responses could be specifically directed against CSC-like cells using the humanised anti-GD2 monoclonal antibody hu14.18K322A. Our findings identify a powerful synergism between MHC-restricted and non-MHC-restricted T cells in the eradication of cancer cells including breast CSCs. Our research suggests that novel immunotherapies may benefit from a two-pronged approach combining γδ T-cell and CD8+ T-cell targeting strategies that triggers effective innate-like and tumour-specific adaptive responses. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

31. Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup

Author

Cowley, Michael, primary, Garfield, Alastair S., additional, Madon-Simon, Marta, additional, Charalambous, Marika, additional, Clarkson, Richard W., additional, Smalley, Matthew J., additional, Kendrick, Howard, additional, Isles, Anthony R., additional, Parry, Aled J., additional, Carney, Sara, additional, Oakey, Rebecca J., additional, Heisler, Lora K., additional, Moorwood, Kim, additional, Wolf, Jason B., additional, and Ward, Andrew, additional

Published
2014
Full Text
View/download PDF

34. Stat3 controls lysosomal-mediated cell death in vivo

Author

Kreuzaler, Peter A., primary, Staniszewska, Anna D., additional, Li, Wenjing, additional, Omidvar, Nader, additional, Kedjouar, Blandine, additional, Turkson, James, additional, Poli, Valeria, additional, Flavell, Richard A., additional, Clarkson, Richard W. E., additional, and Watson, Christine J., additional

Published
2011
Full Text
View/download PDF

37. Microarray Analysis of Apoptosis.

Author

Hollinger, Mannfred A., Davis, Myrtle A., Clarkson, Richard W. E., Boucher, Catherine A., and Watson, Christine J.

Abstract

Apoptotic cell death is a genetically regulated process and the balance between death and survival signals determines the fate of a cell. Apoptosis is important in development and in a number of pathological conditions including cancer and autoimmune diseases. Many transcription factors have been shown to regulate apoptosis in a range of biological systems. However, the downstream target genes and the mechanism of their action have not been clearly defined. The recent advent of gene microarray technology will allow the expression patterns of a large number of genes to be analyzed. Changes in transcription in response to an apoptotic stimulus can be identified and novel pathways defined. [ABSTRACT FROM AUTHOR]

Published
2002
Full Text
View/download PDF

40. Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup.

Author

Cowley, Michael, Garfield, Alastair S., Madon-Simon, Marta, Charalambous, Marika, Clarkson, Richard W., Smalley, Matthew J., Kendrick, Howard, Isles, Anthony R., Parry, Aled J., Carney, Sara, Oakey, Rebecca J., Heisler, Lora K., Moorwood, Kim, Wolf, Jason B., and Ward, Andrew

Subjects
HOMEOSTASIS, PLACENTA, MAMMARY glands, GENOMIC imprinting, MICE as carriers of disease, OBESITY, MAMMALS
Abstract

: A mouse genetic study reveals that a single gene acting in both mother and offspring has a central role in the uniquely mammalian phenomenon of nutrient provisioning through the placenta and the mammary gland. [ABSTRACT FROM AUTHOR]

Published
2014
Full Text
View/download PDF

41. Gene Structure of the Human Metabotropic Glutamate Receptor 5 and Functional Analysis of Its Multiple Promoters in Neuroblastoma and Astroglioma Cells.

Author

Corti, Corrado, Clarkson, Richard W., Crepaldi, Luca, Sala, Cinzia F., Xuereb, John H., and Ferraguti, Francesco

Subjects
*NEUROTRANSMITTER receptors, *PROMOTERS (Genetics), *NEUROBLASTOMA, *ASTROCYTOMAS
Abstract

The metabotropic glutamate receptor 5 (mGluR5) has a discrete tissue expression mainly limited to neural cells. Expression of mGluR5 is developmentally regulated and undergoes dramatic changes in association with neuropathological disorders. We report the complete genomic structure of the mGluR5 gene, which is composed of 11 exons and encompasses ∼563 kbp. Three clusters of multiple transcription initiation sites located on three distinct exons (IA, IB, and II), which undergo alternative splicing, have been identified. The 5'-flanking regions of these exons were isolated and, using a luciferase reporter gene assay, shown to possess active promoter elements in SKN-MC neuroblastoma and U178-MG astroglioma cells. Promoter IA was characterized by a CpG island; promoter IB contained a TATA box, and promoter II possessed three active Oct-1-binding sites. Preferential luciferase activity was observed in SKN-MC concomitant with differential DNA binding activity to several responsive elements, including CREB, Oct-1, C/EBP, and Brn-2. Exposure to growth factors produced enhanced expression of promoters lB and II in astroglioma cells and activation of NF-κB. These results suggest that alternative 5'-splicing and usage of multiple promoters may contribute regulatory mechanisms for tissue- and context-specific expression of the mGluR5 gene. [ABSTRACT FROM AUTHOR]

Published
2003
Full Text
View/download PDF

42. Signal Transduction by the Growth Hormone Receptor.

Author

Waters, Michael J., Rowlinson, Scott W., Clarkson, Richard W., Chen, Chang-Min, Lobie, Peter E., Norstedt, Gunnar, Mertani, Hichem, Morel, Gerard, Brinkworth, Ross, Wells, Christine A., Bastiras, Stan, Robins, Alan R., Muscat, George E., and Barnard, Ross T.

Published
1994
Full Text
View/download PDF

43. Efficient Intravenous Tumor Targeting Using the αvβ6 Integrin-Selective Precision Virotherapy Ad5 NULL -A20.

Author

Davies, James A., Marlow, Gareth, Uusi-Kerttula, Hanni K., Seaton, Gillian, Piggott, Luke, Badder, Luned M., Clarkson, Richard W. E., Chester, John D., Parker, Alan L., Ilett, Elizabeth, and Errington-Mais, Fiona

Subjects
VIROTHERAPY, BREAST cancer, GENETIC vectors, VIRAL genomes, INTRAVENOUS therapy, TRANSGENE expression
Abstract

We previously developed a refined, tumor-selective adenovirus, Ad5NULL-A20, harboring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20-mer peptide (A20) in the fiber knob for selective infection via αvβ6 integrin, a marker of aggressive epithelial cancers. Methods: To ascertain the selectivity of Ad5NULL-A20 for αvβ6-positive tumor cell lines of pancreatic and breast cancer origin, we performed reporter gene and cell viability assays. Biodistribution of viral vectors in mice harboring xenografts with low, medium, and high αvβ6 levels was quantified by qPCR for viral genomes 48 h post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an αvβ6-selective manner, whilst cell killing mediated by oncolytic Ad5NULL-A20 was αvβ6-selective. Biodistribution analysis following intravenous administration into mice bearing breast cancer xenografts demonstrated that Ad5NULL-A20 resulted in significantly reduced liver accumulation coupled with increased tumor accumulation compared to Ad5 in all three models, with tumor-to-liver ratios improved as a function of αvβ6 expression. Conclusions: Ad5NULL-A20-based virotherapies efficiently target αvβ6-integrin-positive tumors following intravenous administration, validating the potential of Ad5NULL-A20 for systemic applications, enabling tumor-selective overexpression of virally encoded therapeutic transgenes. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

44. A 119Sn Mössbauer study of the thermal degradation of organotin stabilisers in PVC

Author

Allen, David W., Brooks, John S., Clarkson, Richard W., Mellor, Malcolm T.J., and Williamson, Alfred G.

Abstract

119mSn Mössbauer studies of the thermal degradation of PVC containing the stabilisers dibutyltinbis (isooctylthioglycollate) (1.2% by weight of the polymer), dioctyltinbis (isooctylthioglycollate (4% by weight of the polymer) and dibutyltinbis (isooctylmaleate) (2% by weight of the polymer) indicate that in each case the stabiliser is converted into the dialkylmonochlorotin ester R2SnCl(X) (X  SCH2CO2C8H17or O2C.CH  CHCO2C8H17), and not into the dialkyltin dichloride, R2SnCl2, as recently suggested by other workers. Comparison of the Mössbauer data for organotin-stabilised PVC samples prepared by both hot-milling and room temperature solvent casting processes indicates that there is little degradation of the polymer (and stabiliser) during the initial hot-milling process.

Published
1980
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results