3 results on '"England GM"'
Search Results
2. Stromal androgen receptor regulates the composition of the microenvironment to influence prostate cancer outcome.
- Author
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Leach DA, Need EF, Toivanen R, Trotta AP, Palethorpe HM, Tamblyn DJ, Kopsaftis T, England GM, Smith E, Drew PA, Pinnock CB, Lee P, Holst J, Risbridger GP, Chopra S, DeFranco DB, Taylor RA, and Buchanan G
- Subjects
- Aged, Aged, 80 and over, Androgens pharmacology, Animals, Apoptosis drug effects, Blotting, Western, Case-Control Studies, Cell Adhesion drug effects, Cell Movement drug effects, Cell Proliferation drug effects, Chromatin Immunoprecipitation, Follow-Up Studies, Humans, Immunoenzyme Techniques, Male, Middle Aged, Myofibroblasts drug effects, Myofibroblasts metabolism, Neoplasm Grading, Neoplasm Invasiveness, Orchiectomy, Prognosis, Prostatic Hyperplasia drug therapy, Prostatic Hyperplasia metabolism, Prostatic Neoplasms drug therapy, Prostatic Neoplasms metabolism, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Receptors, Androgen genetics, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Stromal Cells drug effects, Stromal Cells metabolism, Tissue Array Analysis, Tumor Cells, Cultured, Myofibroblasts pathology, Prostatic Hyperplasia pathology, Prostatic Neoplasms pathology, Receptors, Androgen metabolism, Stromal Cells pathology, Tumor Microenvironment
- Abstract
Androgen receptor (AR) signaling in stromal cells is important in prostate cancer, yet the mechanisms underpinning stromal AR contribution to disease development and progression remain unclear. Using patient-matched benign and malignant prostate samples, we show a significant association between low AR levels in cancer associated stroma and increased prostate cancer-related death at one, three and five years post-diganosis, and in tissue recombination models with primary prostate cancer cells that low stromal AR decreases castration-induced apoptosis. AR-regulation was found to be different in primary human fibroblasts isolated from adjacent to cancerous and non-cancerous prostate epithelia, and to represent altered activation of myofibroblast pathways involved in cell cycle, adhesion, migration, and the extracellular matrix (ECM). Without AR signaling, the fibroblast-derived ECM loses the capacity to promote attachment of both myofibroblasts and cancer cells, is less able to prevent cell-matrix disruption, and is less likely to impede cancer cell invasion. AR signaling in prostate cancer stroma appears therefore to alter patient outcome by maintaining an ECM microenvironment inhibitory to cancer cell invasion. This paper provides comprehensive insight into AR signaling in the non-epithelial prostate microenvironment, and a resource from which the prognostic and therapeutic implications of stromal AR levels can be further explored.
- Published
- 2015
- Full Text
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3. Effects of the antiestrogens tamoxifen, toremifene, and ICI 182,780 on endometrial cancer growth.
- Author
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O'Regan RM, Cisneros A, England GM, MacGregor JI, Muenzner HD, Assikis VJ, Bilimoria MM, Piette M, Dragan YP, Pitot HC, Chatterton R, and Jordan VC
- Subjects
- Animals, Antineoplastic Agents, Hormonal adverse effects, Breast Neoplasms drug therapy, Disease Models, Animal, Estradiol adverse effects, Female, Fulvestrant, Mice, Mice, Nude, Ovariectomy, Endometrial Neoplasms chemically induced, Estradiol analogs & derivatives, Estrogen Antagonists adverse effects, Tamoxifen adverse effects, Toremifene adverse effects
- Abstract
Background: Tamoxifen has been shown to promote the growth of human endometrial tumors implanted in athymic mice, and it has been associated with a twofold to threefold increase in endometrial cancer. Toremifene, a chlorinated derivative of tamoxifen, and ICI 182,780, a pure antiestrogen, are two new antiestrogens being developed for the treatment of breast cancer. The effects of these drugs on endometrial cancer are currently unknown. Our objective was to evaluate the effects of toremifene and ICI 182,780 on the growth of human endometrial cancer in athymic mice., Methods: Athymic, ovariectomized mice were implanted with human endometrial tumors and treated with estrogen, tamoxifen, or the new antiestrogens., Results: The effects of tamoxifen and toremifene on the growth of either tamoxifen-stimulated or tamoxifen-naive endometrial tumors in athymic mice were not substantially different. ICI 182,780 inhibited the growth of tamoxifen-stimulated endometrial cancer, in both the presence and the absence of estrogen., Conclusions: Toremifene and tamoxifen produce identical effects in our endometrial cancer models. Therefore, it is possible that toremifene, like tamoxifen, may be associated with an increased incidence of endometrial cancer. In contrast, ICI 182,780 inhibited tamoxifen-stimulated endometrial cancer, both in the presence and in the absence of estrogen, suggesting that this drug may be safe with regard to the endometrium, even if it is used following tamoxifen, and that it may not result in an increased incidence of endometrial cancer. Indeed, it is even possible that ICI 182,780 may prove useful as an adjuvant agent in early stage endometrial cancer.
- Published
- 1998
- Full Text
- View/download PDF
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