Imperial College London

ProfessorCharlesCoombes

Faculty of MedicineDepartment of Surgery & Cancer

Emeritus Professor of Medical Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2135c.coombes

 
 
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Assistant

 

Mrs Suzy Ford +44 (0)20 7594 2135

 
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Location

 

145ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

976 results found

Bhangu A, Ali SM, Darzi A, Brown G, Tekkis Pet 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

Journal article

Palmieri C, Alifrangis C, Shipway D, Tat T, Watson V, Mackie D, Emson M, Coombes RCet al., 2012, A Randomized Feasibility Study of Docetaxel Versus Vinorelbine in Advanced Breast Cancer, ONCOLOGIST, Vol: 17, ISSN: 1083-7159

Journal article

Rey J, Hu H, Kyle F, Lai C-F, Buluwela L, Coombes RC, Ortlund EA, Ali S, Snyder JP, Barrett AGMet 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

Journal article

Monteiro LJ, Khongkow P, Kongsema M, Morris JR, Man C, Weekes D, Koo C-Y, Gomes AR, Pinto PH, Varghese V, Kenny LM, Coombes RC, Freire R, Medema RH, Lam EW-Fet 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.

Journal article

Lombardo Y, Filipovic A, Molyneux G, Periyasamy M, Giamas G, Hu Y, Trivedi PS, Wang J, Yaguee E, Michel L, Coombes RCet 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

Journal article

Lake MC, Quang-De N, Ali S, Aboagye EOet 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.

Journal article

Pestrin M, Bessi S, Puglisi F, Minisini AM, Masci G, Battelli N, Ravaioli A, Gianni L, Di Marsico R, Tondini C, Gori S, Coombes CR, Stebbing J, Biganzoli L, Buyse M, Di Leo Aet 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

Journal article

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

Journal article

Contractor K, Challapalli A, Tomasi G, Rosso L, Wasan H, Stebbing J, Kenny L, Mangar S, Riddle P, Palmieri C, Al-Nahhas A, Sharma R, Turkheimer F, Coombes RC, Aboagye Eet 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

Journal article

Payne RE, Wang F, Su N, Krell J, Zebrowski A, Yaguee E, Ma X-J, Luo Y, Coombes RCet 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

Journal article

Lee B, Lim AK, Krell J, Satchithananda K, Lewis JS, Coombes RC, Stebbing Jet 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

Conference paper

Lombardo Y, Filipovic A, Molyneux G, Coombes RCet al., 2012, Role of nicastrin in the maintenance of breast cancer stem cells and invasion, CANCER RESEARCH, Vol: 72, ISSN: 0008-5472

Journal article

Stebbing J, Sharma A, North B, Athersuch TJ, Zebrowski A, Pchejetski D, Coombes RC, Nicholson JK, Keun HCet 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

Journal article

Contractor K, Aboagye EO, Jacob J, Challapalli A, Coombes RC, Stebbing Jet 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

Journal article

Fallowfield LJ, Kilburn LS, Langridge C, Snowdon CF, Bliss JM, Coombes RCet 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

Journal article

Bliss JM, Kilburn LS, Coleman RE, Forbes JF, Coates AS, Jones SE, Jassem J, Delozier T, Andersen J, Paridaens R, van de Velde CJH, Lonning PE, Morden J, Reise J, Cisar L, Menschik T, Coombes RCet 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

Journal article

Ross-Innes CS, Stark R, Teschendorff AE, Holmes KA, Ali HR, Dunning MJ, Brown GD, Gojis O, Ellis IO, Green AR, Ali S, Chin S-F, Palmieri C, Caldas C, Carroll JSet al., 2012, Differential oestrogen receptor binding is associated with clinical outcome in breast cancer, NATURE, Vol: 481, Pages: 389-U177, ISSN: 0028-0836

Journal article

Payne RE, Hava NL, Page K, Blighe K, Ward B, Slade M, Brown J, Guttery DS, Zaidi SAA, Stebbing J, Jacob J, Yaguee E, Shaw JA, Coombes RCet 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.

Journal article

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

Journal article

Contractor KB, Kenny LM, Coombes CR, Turkheimer FE, Aboagye EO, Rosso Let 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

Journal article

Palmieri C, Yan K, Owadally W, Shah D, Gojis O, North B, Riddle P, Ahmad R, Lewanski C, Coombes RC, Cleator S, Howell S, Beresford Met al., 2011, Neoadjuvant Chemotherapy-Trastuzumab Versus Neoadjuvant Chemotherapy Followed by Post-Operative Trastuzumab: A Multicentre Study, CANCER RESEARCH, Vol: 71, ISSN: 0008-5472

Journal article

Coombes RC, Reise JA, Lau MR, Carme SC, Searle GE, Huiban M, Burgess P, Noibi S, Koch K, Sapunar F, Saleem Aet 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

Journal article

Dowsett M, Nielsen TO, A'Hern R, Bartlett J, Coombes RC, Cuzick J, Ellis M, Henry NL, Hugh JC, Lively T, McShane L, Paik S, Penault-Llorca F, Prudkin L, Regan M, Salter J, Sotiriou C, Smith IE, Viale G, Zujewski JA, Hayes DFet 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

Journal article

Palmieri C, Januszewski A, Stanway S, Coombes RCet 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

Journal article

Palmieri C, Januszewski A, Stanway S, Coombes RCet 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

Journal article

Horimoto Y, Hartman J, Millour J, Pollock S, Olmos Y, Ho K-K, Coombes RC, Poutanen M, Makela SI, El-Bahrawy M, Speirs V, Lam EW-Fet 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

Journal article

Stebbing J, Thiyagarajan A, Surendrakumar V, Payne R, Krell J, Szydlo R, Peston D, Lewis JS, Coombes RC, Shousha Set 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

Journal article

Berry DA, Ueno NT, Johnson MM, Lei X, Caputo J, Rodenhuis S, Peters WP, Leonard RC, Barlow WE, Tallman MS, Bergh J, Nitz UA, Gianni AM, Basser RL, Zander AR, Coombes RC, Roche H, Tokuda Y, de Vries EGE, Hortobagyi GN, Crown JP, Pedrazzoli P, Bregni M, Demirer Tet 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

Journal article

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