Publications
976 results found
Bhangu A, Ali SM, Darzi A, et al., 2012, Meta-analysis of survival based on resection margin status following surgery for recurrent rectal cancer, COLORECTAL DISEASE, Vol: 14, Pages: 1457-1466, ISSN: 1462-8910
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- Citations: 91
Palmieri C, Alifrangis C, Shipway D, et al., 2012, A Randomized Feasibility Study of Docetaxel Versus Vinorelbine in Advanced Breast Cancer, ONCOLOGIST, Vol: 17, ISSN: 1083-7159
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- Citations: 4
Rey J, Hu H, Kyle F, et al., 2012, Discovery of a New Class of Liver Receptor Homolog-1 (LRH-1) Antagonists: Virtual Screening, Synthesis and Biological Evaluation, CHEMMEDCHEM, Vol: 7, Pages: 1909-1914, ISSN: 1860-7179
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- Citations: 18
Monteiro LJ, Khongkow P, Kongsema M, et al., 2012, The Forkhead Box M1 protein regulates BRIP1 expression and DNA damage repair in epirubicin treatment, Oncogene, Vol: 32, Pages: 4634-4645, ISSN: 1476-5594
FOXM1 is implicated in genotoxic drug resistance but its role and mechanism of action remain unclear. Here, we establish that γH2AX foci, indicative of DNA double-strand breaks (DSBs), accumulate in a time-dependent manner in the drug-sensitive MCF-7 cells but not in the resistant counterparts in response to epirubicin. We find that FOXM1 expression is associated with epirubicin sensitivity and DSB repair. Ectopic expression of FOXM1 can increase cell viability and abrogate DSBs sustained by MCF-7 cells following epirubicin, owing to an enhancement in repair efficiency. Conversely, alkaline comet and γH2AX foci formation assays show that Foxm1-null cells are hypersensitive to DNA damage, epirubicin and γ-irradiation. Furthermore, we find that FOXM1 is required for DNA repair by homologous recombination (HR) but not non-homologous end joining (NHEJ), using HeLa cell lines harbouring an integrated direct repeat green fluorescent protein reporter for DSB repair. We also identify BRIP1 as a direct transcription target of FOXM1 by promoter analysis and chromatin-immunoprecipitation assay. In agreement, depletion of FOXM1 expression by small interfering RNA downregulates BRIP1 expression at the protein and mRNA levels in MCF-7 and the epirubicin-resistant MCF-7 EpiR cells. Remarkably, the requirement for FOXM1 for DSB repair can be circumvented by reintroduction of BRIP1, suggesting that BRIP1 is an important target of FOXM1 in DSB repair. Indeed, like FOXM1, BRIP1 is needed for HR. These data suggest that FOXM1 regulates BRIP1 expression to modulate epirubicin-induced DNA damage repair and drug resistance.
Lombardo Y, Filipovic A, Molyneux G, et al., 2012, Nicastrin regulates breast cancer stem cell properties and tumor growth in vitro and in vivo, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 16558-16563, ISSN: 0027-8424
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- Citations: 60
Lake MC, Quang-De N, Ali S, et al., 2012, Development of a novel molecular sensor for imaging estrogen receptor-coactivator protein-protein interactions, PLoS One, Vol: 7, Pages: 1-9, ISSN: 1932-6203
Anti-estrogens, in particular tissue selective anti-estrogens, have been the bedrock of adjuvant therapy for patients with estrogen receptor alpha (ERα) positive breast cancer. Though current therapies have greatly enhanced patient prognosis, there continues to be an impetus for the development of improved anti-estrogens. ERα is a nuclear receptor transcription factor which activates gene expression through the recruitment of transcriptional coactivator proteins. The SRC family of coactivators, which includes AIB1, has been shown to be of particular importance for ERα mediated transcription. ERα-AIB1 interactions are indicative of gene expression and are inhibited by anti-estrogen treatment. We have exploited the interaction between ERα and AIB1 as a novel method for imaging ERα activity using a split luciferase molecular sensor. By producing a range of ERα ligand binding domain (ER-LBD) and AIB1 nuclear receptor interacting domain (AIB-RID) N- and C-terminal firefly luciferase fragment fusion proteins, constructs which exhibited more than a 10-fold increase in luciferase activity with E2 stimulation were identified. The specificity of the E2-stimulated luciferase activity to ERα-AIB1 interaction was validated through Y537S and L539/540A ER-LBD fusion protein mutants. The primed nature of the split luciferase assay allowed changes in ERα activity, with respect to the protein-protein interactions preceding transcription, to be assessed soon after drug treatment. The novel assay split luciferase detailed in this report enabled modulation of ERα activity to be sensitively imaged in vitro and in living subjects and potentially holds much promise for imaging the efficacy of novel ERα specific therapies.
Pestrin M, Bessi S, Puglisi F, et al., 2012, Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study, BREAST CANCER RESEARCH AND TREATMENT, Vol: 134, Pages: 283-289, ISSN: 0167-6806
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- Citations: 76
Mallarkey G, Coombes RC, 2012, Pathways and biomarkers in breast cancer: latest evidence, THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, Vol: 4, Pages: 157-166, ISSN: 1758-8340
Contractor K, Challapalli A, Tomasi G, et al., 2012, Imaging of cellular proliferation in liver metastasis by [<SUP>18</SUP>F]fluorothymidine positron emission tomography: effect of therapy, PHYSICS IN MEDICINE AND BIOLOGY, Vol: 57, Pages: 3419-3433, ISSN: 0031-9155
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- Citations: 16
Payne RE, Wang F, Su N, et al., 2012, Viable circulating tumour cell detection using multiplex RNA <i>in situ</i> hybridisation predicts progression-free survival in metastatic breast cancer patients, BRITISH JOURNAL OF CANCER, Vol: 106, Pages: 1790-1797, ISSN: 0007-0920
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- Citations: 48
Lee B, Lim AK, Krell J, et al., 2012, The efficacy of axillary ultrasound in the detection of nodal metastasis in breast cancer, 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Lombardo Y, Filipovic A, Molyneux G, et al., 2012, Role of nicastrin in the maintenance of breast cancer stem cells and invasion, CANCER RESEARCH, Vol: 72, ISSN: 0008-5472
Stebbing J, Sharma A, North B, et al., 2012, A metabolic phenotyping approach to understanding relationships between metabolic syndrome and breast tumour responses to chemotherapy, ANNALS OF ONCOLOGY, Vol: 23, Pages: 860-U2, ISSN: 0923-7534
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- Citations: 39
Contractor K, Aboagye EO, Jacob J, et al., 2012, Monitoring early response to taxane therapy in advanced breast cancer with circulating tumor cells and [<SUP>18</SUP>F] 3′-deoxy-3′-fluorothymidine PET: a pilot study, BIOMARKERS IN MEDICINE, Vol: 6, Pages: 231-233, ISSN: 1752-0363
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- Citations: 14
Mieog JSD, Morden JP, Bliss JM, et al., 2012, Carpal tunnel syndrome and musculoskeletal symptoms in postmenopausal women with early breast cancer treated with exemestane or tamoxifen after 2-3 years of tamoxifen: a retrospective analysis of the Intergroup Exemestane Study, LANCET ONCOLOGY, Vol: 13, Pages: 420-432, ISSN: 1470-2045
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- Citations: 50
Fallowfield LJ, Kilburn LS, Langridge C, et al., 2012, Long-term assessment of quality of life in the Intergroup Exemestane Study: 5 years post-randomisation, BRITISH JOURNAL OF CANCER, Vol: 106, Pages: 1062-1067, ISSN: 0007-0920
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- Citations: 34
Bliss JM, Kilburn LS, Coleman RE, et al., 2012, Disease-Related Outcomes With Long-Term Follow-Up: An Updated Analysis of the Intergroup Exemestane Study, JOURNAL OF CLINICAL ONCOLOGY, Vol: 30, Pages: 709-717, ISSN: 0732-183X
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- Citations: 87
Ross-Innes CS, Stark R, Teschendorff AE, et al., 2012, Differential oestrogen receptor binding is associated with clinical outcome in breast cancer, NATURE, Vol: 481, Pages: 389-U177, ISSN: 0028-0836
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- Citations: 1114
Payne RE, Hava NL, Page K, et al., 2012, The presence of disseminated tumour cells in the bone marrow is inversely related to circulating free DNA in plasma in breast cancer dormancy, British Journal of Cancer, Vol: 106, Pages: 375-382, ISSN: 0007-0920
Background:The aim of this study was to gain insight into breast cancer dormancy by examining different measures of minimal residual disease (MRD) over time in relation to known prognostic factors.Methods:Sixty-four primary breast cancer patients on follow-up (a median of 8.3 years post surgery) who were disease free had sequential bone marrow aspirates and blood samples taken for the measurement of disseminated tumour cells (DTCs), circulating tumour cells (CTCs) by CellSearch and qPCR measurement of overlapping (96-bp and 291-bp) amplicons in circulating free DNA (cfDNA).Results:The presence of CTCs was correlated with the presence of DTCs measured by immunocytochemistry (P=0.01) but both were infrequently detected. Increasing cfDNA concentration correlated with ER, HER2 and triple-negative tumours and high tumour grade, and the 291-bp amplicon was inversely correlated with DTCs measured by CK19 qRT-PCR (P=0.047).Conclusion:Our results show that breast cancer patients have evidence of MRD for many years after diagnosis despite there being no overt evidence of disease. The inverse relationship between bone marrow CK19 mRNA and the 291-bp amplicon in cfDNA suggests that an inverse relationship between a measure of cell viability in the bone marrow (DTCs) and cell death in the plasma occurs during the dormancy phase of breast cancer.
Mallarkey G, Coombes RC, 2012, Latest advances in the medical treatment of cancer: a 2011 snapshot, THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, Vol: 4, Pages: 3-8, ISSN: 1758-8340
Contractor KB, Kenny LM, Coombes CR, et al., 2012, Evaluation of limited blood sampling population input approaches for kinetic quantification of [<SUP>18</SUP>F]fluorothymidine PET data, EJNMMI RESEARCH, Vol: 2, ISSN: 2191-219X
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- Citations: 12
Palmieri C, Yan K, Owadally W, et al., 2011, Neoadjuvant Chemotherapy-Trastuzumab Versus Neoadjuvant Chemotherapy Followed by Post-Operative Trastuzumab: A Multicentre Study, CANCER RESEARCH, Vol: 71, ISSN: 0008-5472
Coombes RC, Reise JA, Lau MR, et al., 2011, An Open-Label Positron Emission Tomography Study To Investigate and Quantify Brain and Tumor Penetration of Carbon 11-Labeled Lapatinib in Patients with HER2-Overexpressing Advanced or Metastatic Breast Cancer., CANCER RESEARCH, Vol: 71, ISSN: 0008-5472
Dowsett M, Nielsen TO, A'Hern R, et al., 2011, Assessment of Ki67 in Breast Cancer: Recommendations from the International Ki67 in Breast Cancer Working Group, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 103, Pages: 1656-1664, ISSN: 0027-8874
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- Citations: 1237
Palmieri C, Januszewski A, Stanway S, et al., 2011, Erratum: Irosustat: A first-generation steroid sulfatase inhibitor in breast cancer (Expert Review of Anticancer Therapy (2011) 11:2 179-183), Expert Review of Anticancer Therapy, Vol: 11, ISSN: 1473-7140
Palmieri C, Januszewski A, Stanway S, et al., 2011, Irosustat: a first-generation steroid sulfatase inhibitor in breast cancer (vol 11, pg 179, 2011), EXPERT REVIEW OF ANTICANCER THERAPY, Vol: 11, Pages: 1472-1472, ISSN: 1473-7140
Horimoto Y, Hartman J, Millour J, et al., 2011, ERβ1 Represses FOXM1 Expression through Targeting ERα to Control Cell Proliferation in Breast Cancer, AMERICAN JOURNAL OF PATHOLOGY, Vol: 179, Pages: 1148-1156, ISSN: 0002-9440
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- Citations: 29
Stebbing J, Thiyagarajan A, Surendrakumar V, et al., 2011, Epidermal growth factor receptor status in early stage breast cancer is associated with cellular proliferation but not cross-talk, JOURNAL OF CLINICAL PATHOLOGY, Vol: 64, Pages: 829-831, ISSN: 0021-9746
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- Citations: 4
Mallarkey G, Coombes RC, 2011, Advancing breast cancer therapy by translational research: highlights of the Improving Care and Knowledge through Translational Research (IMPAKT) breast cancer conference., Ther Adv Med Oncol, Vol: 3, Pages: 223-227
Berry DA, Ueno NT, Johnson MM, et al., 2011, High-Dose Chemotherapy With Autologous Stem-Cell Support As Adjuvant Therapy in Breast Cancer: Overview of 15 Randomized Trials, JOURNAL OF CLINICAL ONCOLOGY, Vol: 29, Pages: 3214-3223, ISSN: 0732-183X
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- Citations: 80
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