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Epigenetic Control of Gene Expression in the Normal and Malignant Human Prostate: A Rapid Response Which Promotes Therapeutic Resistance (2019)
Journal Article
Frame, F. M., & Maitland, N. J. (2019). Epigenetic Control of Gene Expression in the Normal and Malignant Human Prostate: A Rapid Response Which Promotes Therapeutic Resistance. International Journal of Molecular Sciences, 20(10), https://doi.org/10.3390/ijms20102437

A successful prostate cancer must be capable of changing its phenotype in response to a variety of microenvironmental influences, such as adaptation to treatment or successful proliferation at a particular metastatic site. New cell phenotypes emerge... Read More

Effects on prostate cancer cells of targeting RNA polymerase III (2019)
Journal Article
Petrie, J. L., Swan, C., Ingram, R. M., Frame, F. M., Collins, A. T., Dumay-Odelot, H., …White, R. J. (2019). Effects on prostate cancer cells of targeting RNA polymerase III. Nucleic Acids Research, 47(8), 3937-3956. https://doi.org/10.1093/nar/gkz128

RNA polymerase (pol) III occurs in two forms, containing either the POLR3G subunit or the related paralogue POLR3GL. Whereas POLR3GL is ubiquitous, POLR3G is enriched in undifferentiated cells. Depletion of POLR3G selectively triggers proliferative a... Read More

Phenotype-independent DNA methylation changes in prostate cancer (2018)
Journal Article
Pellacani, D., Droop, A. P., Frame, F. M., Simms, M. S., Mann, V. M., Collins, A. T., …Maitland, N. J. (2018). Phenotype-independent DNA methylation changes in prostate cancer. The British journal of cancer / Cancer Research Campaign, 119(9), 1133-1143. https://doi.org/10.1038/s41416-018-0236-1

Background Human prostate cancers display numerous DNA methylation changes compared to normal tissue samples. However, definitive identification of features related to the cells’ malignant status has been compromised by the predominance of cells wit... Read More

Inhibition of the PI3K/AKT/mTOR pathway activates autophagy and compensatory Ras/Raf/MEK/ERK signalling in prostate cancer (2017)
Journal Article
Butler, D. E., Marlein, C., Walker, H. F., Frame, F. M., Mann, V. M., Simms, M. S., …Maitland, N. J. (2017). Inhibition of the PI3K/AKT/mTOR pathway activates autophagy and compensatory Ras/Raf/MEK/ERK signalling in prostate cancer. Oncotarget, 8(34), 56698-56713. https://doi.org/10.18632/oncotarget.18082

The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by... Read More

Harvesting human prostate tissue material and culturing primary prostate epithelial cells (2016)
Book Chapter
Frame, F. M., Pellacani, D., Collins, A. T., & Maitland, N. J. (2016). Harvesting human prostate tissue material and culturing primary prostate epithelial cells. In I. J. McEwan (Ed.), The nuclear receptor superfamily: methods and protocols, 181-201. Humana Press. https://doi.org/10.1007/978-1-4939-3724-0_12

In order to fully explore the biology of a complex solid tumor such as prostate cancer, it is desirable to work with patient tissue. Only by working with cells from a tissue can we take into account patient variability and tumor heterogeneity. Cell l... Read More

Stem cells and the role of ETS transcription factors in the differentiation hierarchy of normal and malignant prostate epithelium (2016)
Journal Article
Archer, L. K., Frame, F. M., & Maitland, N. J. (2017). Stem cells and the role of ETS transcription factors in the differentiation hierarchy of normal and malignant prostate epithelium. Journal of Steroid Biochemistry and Molecular Biology, 166, 68-83. https://doi.org/10.1016/j.jsbmb.2016.05.006

Prostate cancer is the most common cancer of men in the UK and accounts for a quarter of all new cases. Although treatment of localised cancer can be successful, there is no cure for patients presenting with invasive prostate cancer and there are les... Read More

An epigenetic reprogramming strategy to resensitize radioresistant prostate cancer cells (2016)
Journal Article
Peitzsch, C., Cojoc, M., Hein, L., Kurth, I., Mäbert, K., Trautmann, F., …Dubrovska, A. (2016). An epigenetic reprogramming strategy to resensitize radioresistant prostate cancer cells. Cancer Research, 76(9), 2637-2651. https://doi.org/10.1158/0008-5472.can-15-2116

Radiotherapy is a mainstay of curative prostate cancer treatment, but risks of recurrence after treatment remain significant in locally advanced disease. Given that tumor relapse can be attributed to a population of cancer stem cells (CSC) that survi... Read More

Low temperature plasmas as emerging cancer therapeutics: the state of play and thoughts for the future (2016)
Journal Article
Hirst, A. M., Frame, F. M., Arya, M., Maitland, N. J., & O’Connell, D. (2016). Low temperature plasmas as emerging cancer therapeutics: the state of play and thoughts for the future. Tumor Biology, 37(6), 7021-7031. https://doi.org/10.1007/s13277-016-4911-7

The field of plasma medicine has seen substantial advances over the last decade, with applications developed for bacterial sterilisation, wound healing and cancer treatment. Low temperature plasmas (LTPs) are particularly suited for medical purposes... Read More

Mechanisms of growth inhibition of primary prostate epithelial cells following gamma irradiation or photodynamic therapy including senscence, necrosis, and autophagy, but not apoptosis (2015)
Journal Article
Frame, F. M., Savoie, H., Bryden, F., Giuntini, F., Mann, V. M., Simms, M. S., …Maitland, N. J. (2016). Mechanisms of growth inhibition of primary prostate epithelial cells following gamma irradiation or photodynamic therapy including senscence, necrosis, and autophagy, but not apoptosis. Cancer medicine, 5(1), 61-73. https://doi.org/10.1002/cam4.553

In comparison to more differentiated cells, prostate cancer stem-like cells are radioresistant, which could explain radio-recurrent prostate cancer. Improvement of radiotherapeutic efficacy may therefore require combination therapy. We have investiga... Read More

Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells (2015)
Journal Article
Hirst, A. M., Simms, M. S., Mann, V. M., Maitland, N. J., O'Connell, D., & Frame, F. M. (2015). Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells. The British journal of cancer / Cancer Research Campaign, 112(9), 1536-1545. https://doi.org/10.1038/bjc.2015.113

Background: In recent years, the rapidly advancing field of low-temperature atmospheric pressure plasmas has shown considerable promise for future translational biomedical applications, including cancer therapy, through the generation of reactive ox... Read More

Low temperature plasma: a novel focal therapy for localized prostate cancer? (2014)
Journal Article
Hirst, A. M., Frame, F. M., Maitland, N. J., & O’Connell, D. (2014). Low temperature plasma: a novel focal therapy for localized prostate cancer?. Biomed research international, 2014, https://doi.org/10.1155/2014/878319

Despite considerable advances in recent years for the focal treatment of localized prostate cancer, high recurrence rates and detrimental side effects are still a cause for concern. In this review, we compare current focal therapies to a potentially... Read More

DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation (2014)
Journal Article
Pellacani, D., Kestoras, D., Droop, A. P., Frame, F. M., Berry, P. A., Lawrence, M. G., …Maitland, N. J. (2014). DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation. Cell Death and Differentiation, 21(5), 761-773. https://doi.org/10.1038/cdd.2013.202

Prostate cancer (CaP) is mostly composed of luminal-like differentiated cells, but contains a small subpopulation of basal cells (including stem-like cells), which can proliferate and differentiate into luminal-like cells. In cancers, CpG island hype... Read More

HDAC inhibitor confers radiosensitivity to prostate stem-like cells (2013)
Journal Article
Frame, F. M., Pellacani, D., Collins, A. T., Simms, M. S., Mann, V. M., Jones, G., …Maitland, N. J. (2013). HDAC inhibitor confers radiosensitivity to prostate stem-like cells. The British journal of cancer / Cancer Research Campaign, 109(12), 3023-3033. https://doi.org/10.1038/bjc.2013.691

Background: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fract... Read More

Differential cytotoxic activity of a novel palladium-based compound on prostate cell lines, primary prostate epithelial cells and prostate stem cells (2013)
Journal Article
Ulukaya, E., Frame, F. M., Cevatemre, B., Pellacani, D., Walker, H., Mann, V. M., …Maitland, N. J. (2013). Differential cytotoxic activity of a novel palladium-based compound on prostate cell lines, primary prostate epithelial cells and prostate stem cells. PloS one, 8(5), https://doi.org/10.1371/journal.pone.0064278

The outcome for patients with advanced metastatic and recurrent prostate cancer is still poor. Therefore, new chemotherapeutics are required, especially for killing cancer stem cells that are thought to be responsible for disease recurrence. In this... Read More

Cancer Stem Cells, Models of Study and Implications of Therapy Resistance Mechanisms (2011)
Book Chapter
Frame, F. M., & Maitland, N. J. (2011). Cancer Stem Cells, Models of Study and Implications of Therapy Resistance Mechanisms. In J. S. Rhim, & R. Kremer (Eds.), Human cell transformation, 105-118. Springer. https://doi.org/10.1007/978-1-4614-0254-1_9

There is now compelling evidence for tumour initiating or cancer stem cells (CSCs) in human cancers. The current evidence of this CSC hypothesis, the CSC phenotype and methods of identification, culture and in vitro modelling will be presented, with... Read More

Regulation of the stem cell marker CD133 is independent of promoter hypermethylation in human epithelial differentiation and cancer (2011)
Journal Article
Pellacani, D., Packer, R. J., Frame, F. M., Oldridge, E. E., Berry, P. A., Labarthe, M., …Maitland, N. J. (2011). Regulation of the stem cell marker CD133 is independent of promoter hypermethylation in human epithelial differentiation and cancer. Molecular Cancer, 10(1), https://doi.org/10.1186/1476-4598-10-94

Background Epigenetic control is essential for maintenance of tissue hierarchy and correct differentiation. In cancer, this hierarchical structure is altered and epigenetic control deregulated, but the relationship between these two phenomena is sti... Read More

Prostate cancer stem cells: do they have a basal or luminal phenotype? (2011)
Journal Article
Maitland, N. J., Frame, F. M., Polson, E. S., Lewis, J. L., & Collins, A. T. (2011). Prostate cancer stem cells: do they have a basal or luminal phenotype?. Hormones and Cancer, 2(1), 47-61. https://doi.org/10.1007/s12672-010-0058-y

The prostate is a luminal secretory tissue whose function is regulated by male sex hormones. Castration produces involution of the prostate to a reversible basal state, and as the majority of prostate cancers also have a luminal phenotype, drug-induc... Read More

Development and limitations of lentivirus vectors as tools for tracking differentiation in prostate epithelial cells (2010)
Journal Article
Frame, F. M., Hager, S., Pellacani, D., Stower, M. J., Walker, H. F., Burns, J. E., …Maitland, N. J. (2010). Development and limitations of lentivirus vectors as tools for tracking differentiation in prostate epithelial cells. Experimental Cell Research, 316(19), 3161-3171. https://doi.org/10.1016/j.yexcr.2010.08.004

To investigate hierarchy in human prostate epithelial cells, we generated recombinant lentiviruses, infected primary cultures and cell lines, and followed their fate in vitro. The lentiviruses combined constitutive promoters including CMV and β-actin... Read More

Prostate cancer stem cells (2008)
Journal Article
Lang, S., Frame, F., & Collins, A. (2009). Prostate cancer stem cells. Journal of Pathology, 217(2), 299-306. https://doi.org/10.1002/path.2478

Despite the discovery over 60 years ago by Huggins and Hodges that prostate cancers respond to androgen deprivation therapy, hormone‐refractory prostate cancer remains a major clinical challenge. There is now mounting evidence that solid tumours orig... Read More

An internal polyadenylation signal substantially increases expression levels of lentivirus-delivered transgenes but has the potential to reduce viral titer in a promoter-dependent manner (2008)
Journal Article
Hager, S., Frame, F. M., Collins, A. T., Burns, J. E., & Maitland, N. J. (2008). An internal polyadenylation signal substantially increases expression levels of lentivirus-delivered transgenes but has the potential to reduce viral titer in a promoter-dependent manner. Human Gene Therapy, 19(8), 840-850. https://doi.org/10.1089/hum.2007.165

In lentiviral gene delivery systems, transgene expression cassettes are commonly cloned without a polyadenylation signal to prevent disruption of full-length lentiviral genomes on mRNA maturation in producer cells. The lack of the polyadenylation sig... Read More