CLAIRE SEEDHOUSE's Outputs (41)

Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML (2023)
Journal Article
James, J. R., Curd, J., Ashworth, J. C., Abuhantash, M., Grundy, M., Seedhouse, C. H., …Thompson, A. (2023). Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML. International Journal of Molecular Sciences, 24(4), Article 4235. https://doi.org/10.3390/ijms24044235

In vivo models of acute myeloid leukemia (AML) are low throughput, and standard liquid culture models fail to recapitulate the mechanical and biochemical properties of the extracellular matrix-rich protective bone marrow niche that contributes to dru... Read More about Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML.

Performance evaluation of a non-invasive one-step multiplex RT-qPCR assay for detection of SARS-CoV-2 direct from saliva (2022)
Journal Article
Jenkins, H. H., Lopez, A. A. T., Tarantini, F. S., Tomlin, H., Scales, D., Lee, I., …Seedhouse, C. (2022). Performance evaluation of a non-invasive one-step multiplex RT-qPCR assay for detection of SARS-CoV-2 direct from saliva. Scientific Reports, 12(1), Article 11553. https://doi.org/10.1038/s41598-022-15616-6

Polymerase chain reaction (PCR) has proven to be the gold-standard for SARS-CoV-2 detection in clinical settings. The most common approaches rely on nasopharyngeal specimens obtained from swabs, followed by RNA extraction, reverse transcription and q... Read More about Performance evaluation of a non-invasive one-step multiplex RT-qPCR assay for detection of SARS-CoV-2 direct from saliva.

Protein Kinase C Epsilon Overexpression Is Associated With Poor Patient Outcomes in AML and Promotes Daunorubicin Resistance Through p-Glycoprotein-Mediated Drug Efflux (2022)
Journal Article
Nicholson, R., Menezes, A., Azevedo, A., Leckenby, A., Davies, S., Seedhouse, C., …Darley, R. L. (2022). Protein Kinase C Epsilon Overexpression Is Associated With Poor Patient Outcomes in AML and Promotes Daunorubicin Resistance Through p-Glycoprotein-Mediated Drug Efflux. Frontiers in Oncology, 12, Article 840046. https://doi.org/10.3389/fonc.2022.840046

The protein kinase C (PKC) family of serine/threonine kinases are pleiotropic signaling regulators and are implicated in hematopoietic signaling and development. Only one isoform however, PKCϵ, has oncogenic properties in solid cancers where it is as... Read More about Protein Kinase C Epsilon Overexpression Is Associated With Poor Patient Outcomes in AML and Promotes Daunorubicin Resistance Through p-Glycoprotein-Mediated Drug Efflux.

Direct RT-qPCR Assay for the Detection of SARS-CoV-2 in Saliva Samples (2022)
Journal Article
Tarantini, F. S., Wu, S., Jenkins, H., Lopez, A. T., Tomlin, H., Hyde, R., …Benest, A. V. (2022). Direct RT-qPCR Assay for the Detection of SARS-CoV-2 in Saliva Samples. Methods and Protocols, 5(2), Article 25. https://doi.org/10.3390/mps5020025

Since mid-2020 there have been complexities and difficulties in the standardisation and administration of nasopharyngeal swabs. Coupled with the variable and/or poor accuracy of lateral flow devices, this has led to increased societal ‘testing fatigu... Read More about Direct RT-qPCR Assay for the Detection of SARS-CoV-2 in Saliva Samples.

Saliva for COVID-19 testing: Simple but useless or an undervalued resource? (2021)
Journal Article
Pijuan-Galito, S., Tarantini, F. S., Tomlin, H., Jenkins, H., Thompson, J. L., Scales, D., …Denning, C. (2021). Saliva for COVID-19 testing: Simple but useless or an undervalued resource?. Frontiers in Virology, 1, Article 778790. https://doi.org/10.3389/fviro.2021.778790

During the COVID-19 pandemic, countries with robust population-based asymptomatic testing were generally successful in controlling virus spread, hence reducing hospitalizations and deaths. This effectiveness inspired widespread asymptomatic surveilla... Read More about Saliva for COVID-19 testing: Simple but useless or an undervalued resource?.

A same‐day assay predicts apoptotic response to combined BCL‐2 and MCL‐1 BH3‐mimetic targeting in multiple myeloma cells (2020)
Journal Article
Grundy, M., Al‐Kaisi, F., Cull, J., Williams, C., Smith, D., & Seedhouse, C. H. (2021). A same‐day assay predicts apoptotic response to combined BCL‐2 and MCL‐1 BH3‐mimetic targeting in multiple myeloma cells. eJHaem, 2(1), 40-47. https://doi.org/10.1002/jha2.133

Recent advances in treatment options for multiple myeloma (MM) have positive impact on patient survival. However, there is a short fall of rapid and reliable assays that can predict patient response to novel agents. The anti-apoptotic proteins B-cell... Read More about A same‐day assay predicts apoptotic response to combined BCL‐2 and MCL‐1 BH3‐mimetic targeting in multiple myeloma cells.

Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia (2020)
Journal Article
Bailey, G. D., Doolan, L., Baskar, A., Smith, L. C., & Seedhouse, C. H. (2020). Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia. Scientific Reports, 10, Article 17695. https://doi.org/10.1038/s41598-020-73782-x

Nucleophosmin is commonly both over-expressed and mutated in acute myeloid leukemia (AML). NPM1 mutations are always heterozygous. In addition, NPM1 has a number of different splice variants with the major variant encoded by exons 1–9 and 11–12 (NPM1... Read More about Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia.

Frequent loss of BTG1 activity and impaired interactions with the Caf1 subunit of the Ccr4–Not deadenylase in non-Hodgkin lymphoma (2020)
Journal Article
Almasmoum, H., Airhihen, B., Seedhouse, C., & Winkler, G. S. (2020). Frequent loss of BTG1 activity and impaired interactions with the Caf1 subunit of the Ccr4–Not deadenylase in non-Hodgkin lymphoma. Leukemia & Lymphoma, 62(2), 281-290. https://doi.org/10.1080/10428194.2020.1827243

© 2020 Informa UK Limited, trading as Taylor & Francis Group. Mutations in the highly similar genes B-cell translocation gene 1 (BTG1) and BTG2 are identified in approximately 10–15% of non-Hodgkin lymphoma cases, which may suggest a direct involve... Read More about Frequent loss of BTG1 activity and impaired interactions with the Caf1 subunit of the Ccr4–Not deadenylase in non-Hodgkin lymphoma.

The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun (2020)
Journal Article
Alhuthali, H. M., Bradshaw, T. D., Lim, K. H., Kam, T. S., & Seedhouse, C. H. (2020). The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun. BMC Cancer, 20, Article 629. https://doi.org/10.1186/s12885-020-07119-2

© 2020 The Author(s). Background: Acute myeloid leukemia (AML) is a heterogenous hematological malignancy with poor long-term survival. New drugs which improve the outcome of AML patients are urgently required. In this work, the activity and mechanis... Read More about The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun.

Increased FLYWCH1 Expression is Negatively Correlated with Wnt/β-catenin Target Gene Expression in Acute Myeloid Leukemia Cells (2019)
Journal Article
Almars, A., Chondrou, P. S., Onyido, E. K., Almozyan, S., Seedhouse, C., Babaei-Jadidi, R., & Nateri, A. S. (2019). Increased FLYWCH1 Expression is Negatively Correlated with Wnt/β-catenin Target Gene Expression in Acute Myeloid Leukemia Cells. International Journal of Molecular Sciences, 20(11), Article 2739. https://doi.org/10.3390/ijms20112739

Acute myeloid leukaemia (AML) is a heterogeneous clonal malignancy of hematopoietic progenitor cells. The Wnt pathway and its downstream targets are tightly regulated by β-catenin. We recently discovered a new protein, FLYWCH1, which can directly bin... Read More about Increased FLYWCH1 Expression is Negatively Correlated with Wnt/β-catenin Target Gene Expression in Acute Myeloid Leukemia Cells.

DNA damage corrects the aberrant cytoplasmic localisation of nucleophosmin in NPM1 mutated acute myeloid leukaemia (2019)
Journal Article
Bailey, G. D., Qutob, H. M. H., Akhtar, A., Russell, N. H., & Seedhouse, C. H. (2019). DNA damage corrects the aberrant cytoplasmic localisation of nucleophosmin in NPM1 mutated acute myeloid leukaemia. British Journal of Haematology, 186(2), 343-347. https://doi.org/10.1111/bjh.15823

Genetic biomarkers predict response to dual BCL-2 and MCL-1 targeting in acute myeloid leukaemia cells (2018)
Journal Article
Grundy, M., Balakrishnan, S., Fox, M., Seedhouse, C., & Russell, N. (2018). Genetic biomarkers predict response to dual BCL-2 and MCL-1 targeting in acute myeloid leukaemia cells. Oncotarget, 9, Article 102. https://doi.org/10.18632/oncotarget.26540

Acute myeloid leukaemia (AML) cells often up-regulate pro-survival members of the BCL-2 protein family, such as BCL-2 and MCL-1, to avoid apoptosis. Venetoclax (ABT-199) targets BCL-2 and has shown promising efficacy in AML but over-expression of MCL... Read More about Genetic biomarkers predict response to dual BCL-2 and MCL-1 targeting in acute myeloid leukaemia cells.

Targeting PARP1 in XRCC1-deficient sporadic invasive breast cancer or preinvasive ductal carcinoma in situ induces synthetic lethality and chemoprevention (2018)
Journal Article
Ali, R., Al-Kawaz, A., Toss, M. S., Green, A. R., Miligy, I. M., Mesquita, K. A., …Madhusudan, S. (2018). Targeting PARP1 in XRCC1-deficient sporadic invasive breast cancer or preinvasive ductal carcinoma in situ induces synthetic lethality and chemoprevention. Cancer Research, 78(24), 6818-6827. https://doi.org/10.1158/0008-5472.CAN-18-0633

© 2018 American Association for Cancer Research. Targeting PARP1 for synthetic lethality is a new strategy for breast cancers harboring germline mutations in BRCA. However, these mutations are rare, and reactivation of BRCA-mediated pathways may resu... Read More about Targeting PARP1 in XRCC1-deficient sporadic invasive breast cancer or preinvasive ductal carcinoma in situ induces synthetic lethality and chemoprevention.

Quantitative assessment of the sensitivity of dormant AML cells to the BAD mimetics ABT-199 and ABT-737 (2018)
Journal Article
Yu, N., Seedhouse, C., Russell, N., & Pallis, M. (2018). Quantitative assessment of the sensitivity of dormant AML cells to the BAD mimetics ABT-199 and ABT-737. Leukemia & Lymphoma, 59(10), 2447-2453. https://doi.org/10.1080/10428194.2018.1434884

Cells from patients with acute myeloid leukaemia (AML) that remain dormant and protected by stromal cells may escape effects of chemotherapy. We modelled dormancy in vitro and investigated the ability of Bcl-2 inhibitors ABT-199 and ABT-737 to overco... Read More about Quantitative assessment of the sensitivity of dormant AML cells to the BAD mimetics ABT-199 and ABT-737.

Predicting effective pro-apoptotic antileukaemic drug combinations using cooperative dynamic BH3 profiling (2018)
Journal Article
Grundy, M., Seedhouse, C., Jones, T., Elmi, L., Hall, M., Graham, A., …Pallis, M. (2018). Predicting effective pro-apoptotic antileukaemic drug combinations using cooperative dynamic BH3 profiling. PLoS ONE, 13(1), Article e0190682. https://doi.org/10.1371/journal.pone.0190682

The BH3-only apoptosis agonists BAD and NOXA target BCL-2 and MCL-1 respectively and co-operate to induce apoptosis. On this basis, therapeutic drugs targeting BCL-2 and MCL-1 might have enhanced activity if used in combination. We identified anti-le... Read More about Predicting effective pro-apoptotic antileukaemic drug combinations using cooperative dynamic BH3 profiling.

A molecular signature of dormancy in CD34+CD38- acute myeloid leukaemia cells (2017)
Journal Article
Al-Asadi, M. G., Brindle, G., Castellanos, M., May, S., Mills, K. I., Russell, N., …Pallis, M. (2017). A molecular signature of dormancy in CD34+CD38- acute myeloid leukaemia cells. Oncotarget, 8(67), 111405-111418. https://doi.org/10.18632/oncotarget.22808

Dormant leukaemia initiating cells in the bone marrow niche are a crucial therapeutic target for total eradication of acute myeloid leukaemia. To study this cellular subset we created and validated an in vitro model employing the cell line TF-1a, tre... Read More about A molecular signature of dormancy in CD34+CD38- acute myeloid leukaemia cells.

Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer (2017)
Journal Article
Shafiee, M. N., Mongan, N. P., Seedhouse, C., Chapman, C., Deen, S., Abu, J., & Atiomo, W. (2017). Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer. Acta Obstetricia et Gynecologica Scandinavica, 96(5), 556-562. https://doi.org/10.1111/aogs.13106

Introduction: Women with polycystic ovary syndrome (PCOS) have a 3-fold higher risk of endometrial cancer (EC). Insulin resistance and hyperlipidaemia may be pertinent factors in the pathogenesis of both conditions. The aim of this study was to inves... Read More about Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer.

Complementary dynamic BH3 profiles predict co-operativity between the multi-kinase inhibitor TG02 and the BH3 mimetic ABT-199 in acute myeloid leukaemia cells (2016)
Journal Article
Pallis, M., Burrows, F., Ryan, J., Grundy, M., Seedhouse, C., Abdul-Aziz, A., …Russell, N. (2016). Complementary dynamic BH3 profiles predict co-operativity between the multi-kinase inhibitor TG02 and the BH3 mimetic ABT-199 in acute myeloid leukaemia cells. Oncotarget, 8(10), https://doi.org/10.18632/oncotarget.8742

Direct co-operation between sensitiser molecules BAD and NOXA in mediating apoptosis suggests that therapeutic agents which sensitise to BAD may complement agents which sensitise to NOXA. Dynamic BH3 profiling is a novel methodology that we have appl... Read More about Complementary dynamic BH3 profiles predict co-operativity between the multi-kinase inhibitor TG02 and the BH3 mimetic ABT-199 in acute myeloid leukaemia cells.

Up-regulation of genes involved in the Insulin signaling pathway (IGF1, PTEN and IGFBP1) in the endometrium may link Polycystic Ovarian Syndrome and endometrial cancer (2016)
Journal Article
Shafiee, M. N., Seedhouse, C., Mongan, N., Chapman, C., Deen, S., Abu, J., & Atiomo, W. (2016). Up-regulation of genes involved in the Insulin signaling pathway (IGF1, PTEN and IGFBP1) in the endometrium may link Polycystic Ovarian Syndrome and endometrial cancer. Molecular and Cellular Endocrinology, 424, 94-101. https://doi.org/10.1016/j.mce.2016.01.019

BACKGROUND

Endometrial cancer (EC) is the most common gynaecological cancer amongst women in the UK. Although previous studies have found that women with polycystic ovary syndrome (PCOS) have at least a three-fold increase in endometrial cancer (E... Read More about Up-regulation of genes involved in the Insulin signaling pathway (IGF1, PTEN and IGFBP1) in the endometrium may link Polycystic Ovarian Syndrome and endometrial cancer.

Caspase-8 polymorphisms result in reduced Alemtuzumab-induced T-cell apoptosis and worse survival after transplantation (2014)
Journal Article

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., …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

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.

Distinct poor prognostic subgroups of acute myeloid leukaemia, FLT3-ITD and P-glycoprotein-positive, have contrasting levels of FOXO1 (2013)
Journal Article
Seedhouse, C., Mills, K. I., Ahluwalia, S., Grundy, M., Shang, S., Burnett, A. K., …Pallis, M. (2014). Distinct poor prognostic subgroups of acute myeloid leukaemia, FLT3-ITD and P-glycoprotein-positive, have contrasting levels of FOXO1. Leukemia Research, 38(1), 131-137. https://doi.org/10.1016/j.leukres.2013.10.030

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., …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.

Low dose rapamycin does not modulate p-glycoprotein function in acute myeloid leukaemia (2007)
Journal Article
Shang, S., Seedhouse, C., Russell, N., & Pallis, M. (2008). Low dose rapamycin does not modulate p-glycoprotein function in acute myeloid leukaemia. Leukemia Research, 32(5), 836-837. https://doi.org/10.1016/j.leukres.2007.08.021

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.

The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia (2002)
Journal Article
Seedhouse, C., Bainton, R., Lewis, M., Harding, A., Russell, N., & Das-Gupta, E. (2002). The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia. Blood, 100(10), 3761-3766. https://doi.org/10.1182/blood-2002-04-1152

Polymorphisms in several DNA repair genes have been described. These polymorphisms may affect DNA repair capacity and modulate cancer susceptibility by means of gene-environment interactions. We investigated DNA repair capacity and its association wi... Read More about The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia.