Abstract:
BACKGROUND:Abiraterone and enzalutamide are novel endocrine treatments that abrogate androgen receptor (AR) signalling in castration-resistant prostate cancer (CRPC). Here, we developed a circulating tumour cells (CTCs)-based assay to evaluate AR expression in real-time in CRPC and investigated nuclear AR expression in CTCs in patients treated with enzalutamide and abiraterone. METHODS:CTCs were captured and characterised using the CellSearch system. An automated algorithm to identify CTCs and quantify AR expression was employed. The primary aim was to evaluate the association between CTC AR expression and prior treatment with abiraterone or enzalutamide. RESULTS:AR expression in CTCs was evaluated in 94 samples from 48 metastatic CRPC patients. We observed large intra-patient heterogeneity of AR expression in CTCs. Prior exposure to abiraterone or enzalutamide was not associated with a change in CTCs AR expression (median intensity and distribution of AR-positive classes). In support of this, we also confirmed maintained nuclear AR expression in tissue samples collected after progression on abiraterone. AR staining also identified additional AR-positive CD45-negative circulating cells that were CK-negative/weak and therefore missed using standard protocols. The number of these events correlated with traditional CTCs and was associated with worse outcome on univariate analysis. CONCLUSIONS:We developed a non-invasive method to monitor AR nuclear expression in CTCs. Our studies confirm nuclear AR expression in CRPC patients progressing on novel endocrine treatments. Owing to the significant heterogeneity of AR expression in CTCs, studies in larger cohorts of patients are required to identify associations with outcome.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Crespo M,van Dalum G,Ferraldeschi R,Zafeiriou Z,Sideris S,Lorente D,Bianchini D,Rodrigues DN,Riisnaes R,Miranda S,Figueiredo I,Flohr P,Nowakowska K,de Bono JS,Terstappen LW,Attard Gdoi
10.1038/bjc.2015.63subject
Has Abstractpub_date
2015-03-31 00:00:00pages
1166-74issue
7eissn
0007-0920issn
1532-1827pii
bjc201563journal_volume
112pub_type
杂志文章abstract::The addition of lapatinib (Tykerb/Tyverb) to capecitabine (Xeloda) delays disease progression more effectively than capecitabine monotherapy in women with previously treated HER2+ metastatic breast cancer (MBC). The quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) method was used to...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
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更新日期:2008-09-02 00:00:00
abstract::Two hundred and thirteen lung tumours of primary site and 42 metastases were heterotransplanted into nude mice with an overall success rate of 44%. There were differences in success between the histological types. Squamous cell and adenocarcinoma had the highest success rate (51% and 43%, respectively) whereas large c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1985.29
更新日期:1985-02-01 00:00:00
abstract::In addition to the direct targeting effects on HER2-positive cells, trastuzumab may have a therapeutic role modulating the activity of the cellular immune system in patients with breast cancer. To investigate this further, the balance of T-regulatory (T(reg)), Th17, natural killer (NK) and NK T (NKT) cells before, dur...
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journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/bjc.2011.7
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abstract:BACKGROUND:Epithelial-to-mesenchymal transition (EMT) is associated with decreased adhesion and acquisition of metastatic potential of breast cancer cells. Epithelial-to-mesenchymal transition is mediated, in part, by two transcription repressors, Snail and Slug, that are known to be targets of the Notch signaling path...
journal_title:British journal of cancer
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更新日期:2010-01-19 00:00:00
abstract::Metabolic reprogramming towards aerobic glycolysis is a common feature of transformed cells and can be driven by a network of transcription factors. It is well established that c-Myc and hypoxia-inducible factor-1α (HIF-1α) contribute to metabolic reprogramming by driving the expression of glycolytic target genes. Mor...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
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更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance in ovarian cancer is the acquisition of DNA methylation. We therefore tested the hypothesis that the DNA hypomethylating agent 5-aza-2'-deoxycytodine (decitabine) can reverse resistance to...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/bjc.2014.116
更新日期:2014-04-15 00:00:00
abstract::Acute inflammatory reactions were induced in rats by the intravenous injection of cellulose sulphate (CS) or an extract of normal rat lung homogenate (LH), or by intraperitoneal injections of Compound 48/80. These treatments greatly increased survival and clonogenic growth in the lungs of rats of intravenously injecte...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1974.189
更新日期:1974-09-01 00:00:00
abstract::Recombinant single-chain fragments (scFv) of the murine anti-MUC1 monoclonal antibody C595 have been produced using the original hybridoma cells as a source of variable heavy (V(H))- and variable light (V(L))-chain-encoding antibody genes. The use of the polymerase chain reaction (PCR), bacteriophage (phage) display t...
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journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究,随机对照试验
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abstract::Large primary breast tumours and extensive lymph node involvement are linked to a high rate of local recurrence after surgery. In 10-20% of such high-risk breast cancer patients, local relapse will occur despite postoperative radiotherapy. In the present study, we investigated whether molecular features, such as angio...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
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更新日期:2003-03-10 00:00:00
abstract::Serum protein induced by vitamin K absence or antagonist II (PIVKAII), hepatoma-specific band of serum gamma-glutamyl transferase (GGTII), and alpha-fetoprotein (AFP) levels were determined in 120 patients with hepatocellular carcinoma (HCC) and 90 patients with cirrhosis. The mean serum concentration of PIVKAII in HC...
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pub_type: 杂志文章
doi:10.1038/sj.bjc.6601018
更新日期:2003-06-16 00:00:00
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journal_title:British journal of cancer
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doi:10.1038/bjc.1997.312
更新日期:1997-01-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1977.49
更新日期:1977-03-01 00:00:00
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doi:10.1038/sj.bjc.6604651
更新日期:2008-10-07 00:00:00
abstract::Canine transmissible venereal sarcoma (CTVS) is a naturally occurring contagious neoplasm which can be transplanted with intact viable cells across major histocompatibility (MHC) barriers within the species and even to other members of the canine family, such as foxes, coyotes, and wolves. After 2 to 4 months of progr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.27
更新日期:1987-02-01 00:00:00
abstract::Fc-receptor-bearing cells forming EA rosettes with antibody-coated human erythrocytes (Ripley) were studied in cell suspensions and in purified preparations of mononuclear cells (MC) from 20 human malignant tumours. The EA rosettes were studied in preparations made by cytocentrifugation and the rosette-forming cells i...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1982.34
更新日期:1982-02-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1971.58
更新日期:1971-09-01 00:00:00
abstract:BACKGROUND:Prenatal supplementation has been inversely associated with childhood, but not with infant, leukaemia. METHODS:Mothers of 443 cases of infant leukaemia diagnosed during 1996-2006 and 324 frequency-matched controls completed interviews. Associations were evaluated by unconditional logistic regression. RESUL...
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更新日期:2010-11-23 00:00:00
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journal_title:British journal of cancer
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更新日期:1995-08-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2018-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:1992-09-01 00:00:00
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doi:10.1038/sj.bjc.6605296
更新日期:2009-10-06 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.123
更新日期:1992-04-01 00:00:00
abstract::The relationship between circulating C-reactive protein concentrations and potential cytokine and receptor mediators (interleukin-6, leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), soluble IL-6 receptor, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and interleukin-8 (IL...
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doi:10.1038/sj.bjc.6602248
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journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.59
更新日期:1997-01-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1997-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-05-25 00:00:00