Publications
976 results found
Abduljabbar R, Al-Kaabi MM, Negm OH, et al., 2015, Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer, BREAST CANCER RESEARCH AND TREATMENT, Vol: 150, Pages: 511-522, ISSN: 0167-6806
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- Citations: 24
Abduljabbar R, Negm OH, Lai C-F, et al., 2015, Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer, BREAST CANCER RESEARCH AND TREATMENT, Vol: 150, Pages: 335-346, ISSN: 0167-6806
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- Citations: 66
Lombardo Y, de Giorgio A, Coombes CR, et al., 2015, Mammosphere Formation Assay from Human Breast Cancer Tissues and Cell Lines, JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, ISSN: 1940-087X
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- Citations: 67
Larner F, Woodley LN, Shousha S, et al., 2015, Zinc isotopic compositions of breast cancer tissue, Metallomics: integrated biometal science, Vol: 7, Pages: 107-112, ISSN: 1756-5901
An early diagnostic biomarker for breast cancer is essential to improve outcome. High precision isotopic analysis, originating in Earth sciences, can detect very small shifts in metal pathways. For the first time, the natural intrinsic Zn isotopic compositions of various tissues in breast cancer patients and controls were determined. Breast cancer tumours were found to have a significantly lighter Zn isotopic composition than the blood, serum and healthy breast tissue in both groups. The Zn isotopic lightness in tumours suggests that sulphur rich metallothionein dominates the isotopic selectivity of a breast tissue cell, rather than Zn-specific proteins. This reveals a possible mechanism of Zn delivery to Zn-sequestering vesicles by metallothionein, and is supported by a similar signature observed in the copper isotopic compositions of one breast cancer patient. This change in intrinsic isotopic compositions due to cancer has the potential to provide a novel early biomarker for breast cancer.
Larner F, Shousha S, Coombes RC, 2015, Zinc isotopes: a novel approach to biomarkers of breast cancer?, BIOMARKERS IN MEDICINE, Vol: 9, Pages: 379-382, ISSN: 1752-0363
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- Citations: 7
Blighe K, Kenny L, Patel N, et al., 2014, Whole Genome Sequence Analysis Suggests Intratumoral Heterogeneity in Dissemination of Breast Cancer to Lymph Nodes, PLOS One, Vol: 9, ISSN: 1932-6203
Background: Intratumoral heterogeneity may help drive resistance to targetedtherapies in cancer. In breast cancer, the presence of nodal metastases is a keyindicator of poorer overall survival. The aim of this study was to identify somaticgenetic alterations in early dissemination of breast cancer by whole genome nextgeneration sequencing (NGS) of a primary breast tumor, a matched locally-involvedaxillary lymph node and healthy normal DNA from blood.Methods: Whole genome NGS was performed on 12 mg (range 11.1–13.3 mg) ofDNA isolated from fresh-frozen primary breast tumor, axillary lymph node andperipheral blood following the DNA nanoball sequencing protocol. Single nucleotidevariants, insertions, deletions, and substitutions were identified through abioinformatic pipeline and compared to CIN25, a key set of genes associated withtumor metastasis.Results: Whole genome sequencing revealed overlapping variants between thetumor and node, but also variants that were unique to each. Novel mutations uniqueto the node included those found in two CIN25 targets, TGIF2 and CCNB2, whichare related to transcription cyclin activity and chromosomal stability, respectively,and a unique frameshift in PDS5B, which is required for accurate sister chromatidsegregation during cell division. We also identified dominant clonal variants thatprogressed from tumor to node, including SNVs in TP53 and ARAP3, whichmediates rearrangements to the cytoskeleton and cell shape, and an insertion in TOP2A, the expression of which is significantly associated with tumor proliferationand can segregate breast cancers by outcome.Conclusion: This case study provides preliminary evidence that primary tumor andearly nodal metastasis have largely overlapping somatic genetic alterations. Therewere very few mutations unique to the involved node. However, significantconclusions regarding early dissemination needs analysis of a larger number ofpatient samples.
Palmieri C, Cleator S, Kilburn LS, et al., 2014, NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer, BREAST CANCER RESEARCH AND TREATMENT, Vol: 148, Pages: 581-590, ISSN: 0167-6806
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- Citations: 60
Filipovic A, Lombardo Y, Faronato M, et al., 2014, Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells (vol 148, pg 455, 2014), BREAST CANCER RESEARCH AND TREATMENT, Vol: 148, Pages: 463-463, ISSN: 0167-6806
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- Citations: 1
Filipovic A, Lombardo Y, Fronato M, et al., 2014, Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells, BREAST CANCER RESEARCH AND TREATMENT, Vol: 148, Pages: 455-462, ISSN: 0167-6806
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- Citations: 16
Rudraraju B, Droog M, Abdel-Fatah TMA, et al., 2014, Phosphorylation of activating transcription factor-2 (ATF-2) within the activation domain is a key determinant of sensitivity to tamoxifen in breast cancer, BREAST CANCER RESEARCH AND TREATMENT, Vol: 147, Pages: 295-309, ISSN: 0167-6806
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- Citations: 13
Xu Y, Zhang H, Lit LC, et al., 2014, The Kinase LMTK3 Promotes Invasion in Breast Cancer Through GRB2-Mediated Induction of Integrin β<sub>1</sub>, SCIENCE SIGNALING, Vol: 7, ISSN: 1945-0877
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- Citations: 31
Elliott KM, Dent J, Stanczyk FZ, et al., 2014, Effects of aromatase inhibitors and body mass index on steroid hormone levels in women with early and advanced breast cancer, BRITISH JOURNAL OF SURGERY, Vol: 101, Pages: 939-948, ISSN: 0007-1323
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- Citations: 13
Lombardo Y, Faronato M, Filipovic A, et al., 2014, Nicastrin and Notch4 drive endocrine therapy resistance and epithelial to mesenchymal transition in MCF7 breast cancer cells, Breast Cancer Research, Vol: 16, ISSN: 1465-542X
IntroductionResistance to anti-estrogen therapies is a major cause of disease relapse and mortality in estrogen receptor alpha (ERα)-positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependence of breast cancer cells on Notch signalling. Here, we investigated the contribution of Nicastrin and Notch signalling in endocrine-resistant breast cancer cells.MethodsWe used two models of endocrine therapies resistant (ETR) breast cancer: tamoxifen-resistant (TamR) and long-term estrogen-deprived (LTED) MCF7 cells. We evaluated the migratory and invasive capacity of these cells by Transwell assays. Expression of epithelial to mesenchymal transition (EMT) regulators as well as Notch receptors and targets were evaluated by real-time PCR and western blot analysis. Moreover, we tested in vitro anti-Nicastrin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. Finally, we generated stable Nicastrin overexpessing MCF7 cells and evaluated their EMT features and response to tamoxifen.ResultsWe found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and displayed increased levels of Nicastrin and Notch targets. Interestingly, we detected higher level of Notch4 but lower levels of Notch1 and Notch2 suggesting a switch to signalling through different Notch receptors after acquisition of resistance. Anti-Nicastrin monoclonal antibodies and the GSI PF03084014 were effective in blocking the Nicastrin/Notch4 axis and partially inhibiting the EMT process. As a result of this, cell migration and invasion were attenuated and the stem cell-like population was significantly reduced. Genetic silencing of Nicastrin and Notch4 led to equivalent effects. Finally, stable overexpression of Nicastrin was sufficient to make MCF7 unresponsive to tamoxifen by Notch4 activation.ConclusionsETR cells express high levels of Nicastrin and Notch4, whose activation ultimately drives invasive be
Forbes JF, Dowsett M, Bradley R, et al., 2014, Patient-level meta-analysis of randomized trials of aromatase inhibitors (AI) versus tamoxifen (Tam)., 50th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
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- Citations: 2
Roca-Alonso L, Castellano L, Mills A, et al., 2014, Myocardial miR-30 down-regulation triggered by doxorubicin drives alterations in the beta-adrenergic pathway and enhances apoptosis, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 16, Pages: 115-115, ISSN: 1388-9842
Fraser SP, Ozerlat-Gunduz I, Brackenbury WJ, et al., 2014, Regulation of voltage-gated sodium channel expression in cancer: hormones, growth factors and auto-regulation, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 369, ISSN: 0962-8436
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- Citations: 98
Djamgoz MBA, Coombes RC, Schwab A, 2014, Ion transport and cancer: from initiation to metastasis Introduction, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 369, ISSN: 0962-8436
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- Citations: 64
Zhou Y, Hu Y, Yang M, et al., 2014, The miR-106b similar to 25 cluster promotes bypass of doxorubicin-induced senescence and increase in motility and invasion by targeting the E-cadherin transcriptional activator EP300, Cell Death and Differentiation, Vol: 21, Pages: 462-474, ISSN: 1350-9047
Resistance to chemotherapeutic treatment, which is indirectly responsible for many cancer deaths, is normally associated with an aggressive phenotype including increased cell motility and acquisition of invasive properties. Here we describe how breast cancer cells overcome doxorubicin-induced senescence and become drug resistant by overexpression of the microRNA (miR)-106b∼25 cluster. Although all three miRs in the cluster contribute to the generation of doxorubicin resistance, miR-25 is the major contributor to this phenotype. All three miRs in this cluster target EP300, a transcriptional activator of E-cadherin, resulting in cells acquiring a phenotype characteristic of cells undergoing epithelial-to-mesenchymal transition (EMT), including an increase in both cell motility and invasion, as well as the ability to proliferate after treatment with doxorubicin. These findings provide a novel drug resistance/EMT regulatory pathway controlled by the miR-106b∼25 cluster by targeting a transcriptional activator of E-cadherin.
Huang B, Omoto Y, Iwase H, et al., 2014, Differential expression of estrogen receptor alpha, beta 1, and beta 2 in lobular and ductal breast cancer, Proceedings of the National Academy of Sciences of the United States of America, Vol: 111, Pages: 1933-1938, ISSN: 0027-8424
The role of estrogen receptor (ER) α as a target in treatment of breast cancer is clear, but those of ERβ1 and ERβ2 in the breast remain unclear. We have examined expression of all three receptors in surgically excised breast samples from two archives: (i): 187 invasive ductal breast cancer from a Japanese study; and (ii) 20 lobular and 24 ductal cancers from the Imperial College. Samples contained normal areas, areas of hyperplasia, and in situ and invasive cancer. In the normal areas, ERα was expressed in not more than 10% of epithelium, whereas approximately 80% of epithelial cells expressed ERβ. We found that whereas ductal cancer is a highly proliferative, ERα-positive, ERβ-negative disease, lobular cancer expresses both ERα and ERβ but with very few Ki67-positive cells. ERβ2 was expressed in 32% of the ductal cancers, of which 83% were postmenopausal. In all ERβ2-positive cancers the interductal space was filled with dense collagen, and cell nuclei expressed hypoxia-inducible factor 1α. ERβ2 expression was not confined to malignant cells but was strong in stromal, immune, and endothelial cells. In most of the high-grade invasive ductal cancers neither ERα nor ERβ was expressed, but in the high-grade lobular cancer ERβ was lost and ERα and Ki67 expression were abundant. The data show a clear difference in ER expression between lobular and ductal breast cancer and suggest (i) that tamoxifen may be more effective in late than in early lobular cancer and (ii) a potential role for ERβ agonists in preventing in situ ductal cancers from becoming invasive.
Brooke GN, Powell SM, Lavery DN, et al., 2014, Engineered repressors are potent inhibitors of androgen receptor activity, Oncotarget, Vol: 5, Pages: 959-969, ISSN: 1949-2553
Prostate cancer growth is dependent upon the Androgen Receptor (AR) pathway, hence therapies for this disease often target this signalling axis. Such therapies are successful in the majority of patients but invariably fail after a median of 2 years and tumours progress to a castrate resistant stage (CRPC). Much evidence exists to suggest that the AR remains key to CRPC growth and hence remains a valid therapeutic target. Here we describe a novel method to inhibit AR activity, consisting of an interaction motif, that binds to the AR ligand-binding domain, fused to repression domains. These ‘engineered repressors’ are potent inhibitors of AR activity and prostate cancer cell growth and importantly inhibit the AR under circumstances in which conventional therapies would be predicted to fail, such as AR mutation and altered cofactor levels.
Sarajlic A, Filipovic A, Janjic V, et al., 2014, The role of genes co-amplified with nicastrin in breast invasive carcinoma, BREAST CANCER RESEARCH AND TREATMENT, Vol: 143, Pages: 393-401, ISSN: 0167-6806
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- Citations: 6
Challapalli A, Barwick T, Tomasi G, et al., 2014, Exploring the potential of [<SUP>11</SUP>C]choline-PET/CT as a novel imaging biomarker for predicting early treatment response in prostate cancer, NUCLEAR MEDICINE COMMUNICATIONS, Vol: 35, Pages: 20-29, ISSN: 0143-3636
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- Citations: 19
Frampton AE, Castellano L, Colombo T, et al., 2014, MicroRNAs Cooperatively Inhibit a Network of Tumor Suppressor Genes to Promote Pancreatic Tumor Growth and Progression, GASTROENTEROLOGY, Vol: 146, Pages: 268-+, ISSN: 0016-5085
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- Citations: 132
Caballero OL, Shousha S, Zhao Q, et al., 2014, Expression of Cancer/Testis genes in ductal carcinoma in situ and benign lesions of the breast., Oncoscience, Vol: 1, Pages: 14-20, ISSN: 2331-4737
Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in cancer patients and this feature makes them attractive targets for immunotherapy-based approaches. We have previously reported that CTs are relatively commonly expressed in estrogen receptor (ER) negative, high risk carcinomas. In this study, we examined the expression of selected CT genes in ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and benign proliferative lesions of the breast. ER negative DCIS were found to be associated with significant CT gene expression together with HER2 positivity and a marked stromal immune response.
Ignatiadis M, Riethdorf S, Bidard F-C, et al., 2014, International study on inter-reader variability for circulating tumor cells in breast cancer, BREAST CANCER RESEARCH, Vol: 16, ISSN: 1465-5411
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- Citations: 36
Stebbing J, Harding V, Urch CE, et al., 2014, The prognostic role of circulating tumor cells in heavily pretreated individuals with a low life expectancy, FUTURE ONCOLOGY, Vol: 10, Pages: 2555-2560, ISSN: 1479-6694
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- Citations: 1
Myatt SS, Kongsema M, Man CW-Y, et al., 2013, SUMOylation inhibits FOXM1 activity and delays mitotic transition, Oncogene, Vol: 33, Pages: 4316-4329, ISSN: 1476-5594
The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response.
Filipovic A, Green A, Hsu R, et al., 2013, Nicastrin RNA in situ hybridization (RNAScope®) reveals estrogen receptor negative breast cancer patients at risk of metastatic relapse and could serve as companion diagnostic for anti-nicastrin monoclonal antibody therapy, CANCER RESEARCH, Vol: 73, ISSN: 0008-5472
Ottaviani S, Brooke GN, O'Hanlon-Brown C, et al., 2013, Characterisation of the androgen regulation of glycine <i>N</i>-methyltransferase in prostate cancer cells, JOURNAL OF MOLECULAR ENDOCRINOLOGY, Vol: 51, Pages: 301-312, ISSN: 0952-5041
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- Citations: 13
Lai C-F, Flach KD, Alexi X, et al., 2013, Co-regulated gene expression by oestrogen receptor α and liver receptor homolog-1 is a feature of the oestrogen response in breast cancer cells, NUCLEIC ACIDS RESEARCH, Vol: 41, Pages: 10228-10240, ISSN: 0305-1048
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- Citations: 36
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