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Dr CLAIRE SEEDHOUSE's Outputs (41)

Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy (2014)
Journal Article
Albarakati, N., Abdel-Fatah, T. M., Doherty, R., Russell, R., Agarwal, D., Moseley, P., Perry, C., Arora, A., Alsubhi, N., Seedhouse, C., Rakha, E. A., Green, A., Ball, G., Chan, S., Caldas, C., Ellis, I. O., & Madhusudan, S. (2015). Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy. Molecular Oncology, 9(1), 204-217. https://doi.org/10.1016/j.molonc.2014.08.001

BRCA1, a key factor in homologous recombination (HR) repair may also regulate base excision repair (BER). Targeting BRCA1‐BER deficient cells by blockade of ATM and DNA‐PKcs could be a promising strategy in breast cancer. We investigated BRCA1, XRCC1... Read More about Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy.

Targeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy (2014)
Journal Article
Abbotts, R., Jewell, R., Nsengimana, J., Maloney, D. J., Simeonov, A., Seedhouse, C., Elliott, F., Laye, J., Walker, C., Jadhav, A., Grabowska, A., Ball, G., Patel, P. M., Newton-Bishop, J., Wilson III, D. M., & Madhusudan, S. (2014). Targeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy. Oncotarget, 5(10), 3273-3286. https://doi.org/10.18632/oncotarget.1926

Phosphatase and tensin homolog (PTEN) loss is associated with genomic instability. APE1 is a key player in DNA base excision repair (BER) and an emerging drug target in cancer. We have developed small molecule inhibitors against APE1 repair nuclease... Read More about Targeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy.

Efficacy of RNA polymerase II inhibitors in targeting dormant leukaemia cells (2013)
Journal Article
Pallis, M., Burrows, F., Whittall, A., Boddy, N., Seedhouse, C., & Russell, N. (2013). Efficacy of RNA polymerase II inhibitors in targeting dormant leukaemia cells. BMC Pharmacology and Toxicology, 14(June), Article 11. https://doi.org/10.1186/2050-6511-14-32

Background
Dormant cells are characterised by low RNA synthesis. In contrast, cancer cells can be addicted to high RNA synthesis, including synthesis of survival molecules. We hypothesised that dormant cancer cells, already low in RNA, might be sens... Read More about Efficacy of RNA polymerase II inhibitors in targeting dormant leukaemia cells.

Ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase inhibition is synthetically lethal in XRCC1 deficient ovarian cancer cells (2013)
Journal Article
Sultana, R., Abdel-Fatah, T., Perry, C., Moseley, P., Albarakti, N., Mohan, V., Seedhouse, C., Chan, S., & Madhusudan, S. (2013). Ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase inhibition is synthetically lethal in XRCC1 deficient ovarian cancer cells. PLoS ONE, 8(2), Article e57098. https://doi.org/10.1371/journal.pone.0057098

Introduction
Ataxia telangiectasia mutated and Rad3 Related (ATR) protein kinase is a key sensor of single-stranded DNA associated with stalled replication forks and repair intermediates generated during DNA repair. XRCC1 is a critical enzyme in sin... Read More about Ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase inhibition is synthetically lethal in XRCC1 deficient ovarian cancer cells.

Targeting of CD34+CD38- cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in acute Myeloid Leukaemia (2012)
Journal Article
Jawad, M., Yu, N., Seedhouse, C., Tandon, K., Russell, N. H., & Pallis, M. (2012). Targeting of CD34+CD38- cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in acute Myeloid Leukaemia. BMC Cancer, https://doi.org/10.1186/1471-2407-12-431

Background
The CD34+CD38- subset of AML cells is enriched for resistance to current chemotherapeutic agents and considered to contribute to disease progression and relapse in Acute Myeloid Leukaemia (AML) patients following initial treatment.

Met... Read More about Targeting of CD34+CD38- cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in acute Myeloid Leukaemia.

The multi-kinase inhibitor TG02 overcomes signalling activation by survival factors to deplete MCL1 and XIAP and induce cell death in primary acute myeloid leukaemia cells (2012)
Journal Article
Pallis, M., Abdul-Aziz, A., Burrows, F., Seedhouse, C., Grundy, M., & Russell, N. (2012). The multi-kinase inhibitor TG02 overcomes signalling activation by survival factors to deplete MCL1 and XIAP and induce cell death in primary acute myeloid leukaemia cells. British Journal of Haematology, 159(2), 191-203. https://doi.org/10.1111/bjh.12018

The novel multi-kinase inhibitor TG02 has selectivity against cell cycle and transcriptional cyclin dependent kinases (CDKs) as well as fms-like tyrosine kinase receptor-3 (FLT3). Inhibition of transcriptional CDKs preferentially depletes short-lived... Read More about The multi-kinase inhibitor TG02 overcomes signalling activation by survival factors to deplete MCL1 and XIAP and induce cell death in primary acute myeloid leukaemia cells.

P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA (2011)
Journal Article
Grundy, M., Seedhouse, C., Russell, N. H., & Pallis, M. (2011). P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA. BMC Cancer, 11, Article 254. https://doi.org/10.1186/1471-2407-11-254

Background
Aurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently over-expressed in a variety of human malignancies. Over-expression of... Read More about P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA.

The FLT3 internal tandem duplication mutation is a secondary target of the aurora B kinase inhibitor AZD1152-HQPA in acute myelogenous leukemia cells (2010)
Journal Article
Grundy, M., Seedhouse, C., Shang, S., Richardson, J., Russell, N., & Pallis, M. (2010). The FLT3 internal tandem duplication mutation is a secondary target of the aurora B kinase inhibitor AZD1152-HQPA in acute myelogenous leukemia cells. Molecular Cancer Therapeutics, 9(3), https://doi.org/10.1158/1535-7163.MCT-09-1144

Aurora kinases play an essential role in orchestrating chromosome alignment, segregation, and cytokinesis during mitotic progression and both aurora-A and B are frequently overexpressed in a variety of human malignancies. In this study, we report the... Read More about The FLT3 internal tandem duplication mutation is a secondary target of the aurora B kinase inhibitor AZD1152-HQPA in acute myelogenous leukemia cells.

Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine (2009)
Journal Article
Seedhouse, C., Grundy, M., Shang, S., Ronan, J., Pimblett, H., Russell, N., & Pallis, M. (2009). Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine. Clinical Cancer Research, 15(23), 7291-7298. https://doi.org/10.1158/1078-0432.CCR-09-1222

Purpose: Acute myeloid leukemia cells with an internal tandem duplication mutation of FLT3 (FLT3-ITD) have effective DNA repair mechanisms on exposure to drugs. Despite this, the phenotype is not associated with primary resistant disease. We show def... Read More about Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine.

Analysis of factors that affect in vitro chemosensitivity of leukaemic stem and progenitor cells to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukaemia (2009)
Journal Article
Jawad, M., Seedhouse, C., Mony, U., Grundy, M., Russell, N. H., & Pallis, M. (2010). Analysis of factors that affect in vitro chemosensitivity of leukaemic stem and progenitor cells to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukaemia. Leukemia, 24, 74-80. https://doi.org/10.1038/leu.2009.199

Relapse in acute myeloid leukaemia (AML) is considered to result from the persistence of drug-resistant leukaemic stem and progenitor cells (LSPC) within a bone marrow ‘niche’ microenvironment. Identifying novel agents that have the potential to targ... Read More about Analysis of factors that affect in vitro chemosensitivity of leukaemic stem and progenitor cells to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukaemia.

Resistance to FLT3 inhibition in an in vitro model of primary AML cells with a stem cell phenotype in a defined microenvironment (2008)
Journal Article
(2008). Resistance to FLT3 inhibition in an in vitro model of primary AML cells with a stem cell phenotype in a defined microenvironment. Leukemia, 22, 1395-1401. https://doi.org/10.1038/leu.2008.125

Relapse in acute myeloid leukaemia (AML) is mediated by survival of leukaemic stem cells following remission-induction chemotherapy. It would therefore be useful to identify therapeutic agents that target leukaemic stem cells. We devised a flow cytom... Read More about Resistance to FLT3 inhibition in an in vitro model of primary AML cells with a stem cell phenotype in a defined microenvironment.

P-glycoprotein is downregulated in KG1a-primitive leukemia cells by LDL cholesterol deprivation and by HMG-CoA reductase inhibitors (2007)
Journal Article
Connelly Smith, L., Pattinson, J., Grundy, M., Shang, S., Seedhouse, C., Russell, N., & Pallis, M. (2007). P-glycoprotein is downregulated in KG1a-primitive leukemia cells by LDL cholesterol deprivation and by HMG-CoA reductase inhibitors. Experimental Hematology, 35(12), 1793-1800. https://doi.org/10.1016/j.exphem.2007.07.017

Objective
P-glycoprotein (pgp) is a membrane transporter encoded by the multidrug resistance (MDR1, ABCB1) gene. Pgp is a poor prognostic factor in elderly patients with acute myeloid leukemia (AML). In addition to its role in drug efflux, pgp has b... Read More about P-glycoprotein is downregulated in KG1a-primitive leukemia cells by LDL cholesterol deprivation and by HMG-CoA reductase inhibitors.

Vascular endothelial growth factor induction by prostaglandin E2 in human airway smooth muscle cells is mediated by E prostanoid EP 2/EP4 receptors and SP-1 transcription factor binding sites (2005)
Journal Article
Bradbury, D., Clarke, D., Seedhouse, C., Corbettt, L., Stocks, J., & Knox, A. (2005). Vascular endothelial growth factor induction by prostaglandin E2 in human airway smooth muscle cells is mediated by E prostanoid EP 2/EP4 receptors and SP-1 transcription factor binding sites. Journal of Biological Chemistry, 280(34), 29993-30000. https://doi.org/10.1074/jbc.M414530200

Prostaglandin E2 (PGE2) can increase vascular endothelial growth factor A (VEGF-A) production but the mechanisms involved are unclear. Here we characterized the transcriptional mechanisms involved in human airway smooth muscle cells (HASMC). PGE2 inc... Read More about Vascular endothelial growth factor induction by prostaglandin E2 in human airway smooth muscle cells is mediated by E prostanoid EP 2/EP4 receptors and SP-1 transcription factor binding sites.

Advances in the understanding of susceptibility to treatment-related acute myeloid leukaemia (2004)
Journal Article
Seedhouse, C., & Russell, N. (2004). Advances in the understanding of susceptibility to treatment-related acute myeloid leukaemia. British Journal of Haematology, 137(6), 513-529. https://doi.org/10.1111/j.1365-2141.2007.06613.x

Treatment-related acute myeloid leukaemia (t-AML) is a devastating complication following exposure to the cytotoxic and genotoxic agents used to treat a primary malignancy. Whilst the incidence of t-AML is rising, it still only occurs in a minority o... Read More about Advances in the understanding of susceptibility to treatment-related acute myeloid leukaemia.

Clonal haemopoiesis may occur after conventional chemotherapy and is associated with accelerated telomere shortening and defects in the NQO1 pathway; possible mechanisms leading to an increased risk of t-AML/MDS (2004)
Journal Article
Fern, L., Pallis, M., Carter, G. I., Seedhouse, C., Russell, N., & Byrne, J. (2004). Clonal haemopoiesis may occur after conventional chemotherapy and is associated with accelerated telomere shortening and defects in the NQO1 pathway; possible mechanisms leading to an increased risk of t-AML/MDS. British Journal of Haematology, 126(1), 63-71. https://doi.org/10.1111/j.1365-2141.2004.05006.x

The molecular pathogenesis of therapy-related acute myeloid leukaemia/myelodysplastic syndrome (t-AML/MDS) remains uncertain. However, clonal haemopoiesis may develop following stem cell transplantation and precede the development of t-AML/MDS. Moreo... Read More about Clonal haemopoiesis may occur after conventional chemotherapy and is associated with accelerated telomere shortening and defects in the NQO1 pathway; possible mechanisms leading to an increased risk of t-AML/MDS.

Polymorphisms in Genes Involved in Homologous Recombination Repair Interact to Increase the Risk of Developing Acute Myeloid Leukemia (2004)
Journal Article
Seedhouse, C., Faulkner, R., Ashraf, N., Das-Gupta, E., & Russell, N. (2004). Polymorphisms in Genes Involved in Homologous Recombination Repair Interact to Increase the Risk of Developing Acute Myeloid Leukemia. Clinical Cancer Research, 10(8), 2675–2680. https://doi.org/10.1158/1078-0432.CCR-03-0372

Purpose: Double-strand break repair via homologous recombination is essential in maintaining genetic integrity. RAD51 and XRCC3 are involved in the repair of DNA by this pathway, and polymorphisms have been identified in both the RAD51 (RAD51-G135C)... Read More about Polymorphisms in Genes Involved in Homologous Recombination Repair Interact to Increase the Risk of Developing Acute Myeloid Leukemia.

Resistance to spontaneous apoptosis in acute myeloid leukaemia blasts is associated with p-glycoprotein expression and function, but not with the presence of FLT3 internal tandem duplications (2003)
Journal Article
Pallis, M., Turzanski, J., Grundy, M., Seedhouse, C., & Russell, N. (2003). Resistance to spontaneous apoptosis in acute myeloid leukaemia blasts is associated with p-glycoprotein expression and function, but not with the presence of FLT3 internal tandem duplications. British Journal of Haematology, 120(6), 1009-1016. https://doi.org/10.1046/j.1365-2141.2003.04210.x

The ability of acute myeloid leukaemia (AML) blasts to survive in culture has been associated with poor patient response to chemotherapy. Other biological factors predicting an adverse outcome include p-glycoprotein (pgp) expression, which is associa... Read More about Resistance to spontaneous apoptosis in acute myeloid leukaemia blasts is associated with p-glycoprotein expression and function, but not with the presence of FLT3 internal tandem duplications.

Flow cytometric measurement of phosphorylated STAT5 in AML: Lack of specific association with FLT3 internal tandem duplications (2003)
Journal Article
Pallis, M., Seedhouse, C., Grundy, M., & Russell, N. (2003). Flow cytometric measurement of phosphorylated STAT5 in AML: Lack of specific association with FLT3 internal tandem duplications. Leukemia Research, 27(9), 803-805. https://doi.org/10.1016/S0145-2126%2803%2900012-2

STAT5 phosphorylation has been noted in 69–95% of AML cases by Western blotting. We used flow cytometry to measure phosphorylated STAT5 on a semi-quantitative scale. The method was validated on K562 cells, which constitutively express phosphorylated... Read More about Flow cytometric measurement of phosphorylated STAT5 in AML: Lack of specific association with FLT3 internal tandem duplications.