Abstract：
:Chordomas are radio- and chemo-resistant tumours and metastasise in as many as 40% of patients. The aim of this study was to identify potential molecular targets for the treatment of chordoma. In view of the reported association of chordoma and tuberous sclerosis complex syndrome, and the available therapeutic agents against molecules in the PI3K/AKT/TSC1/TSC2/mTOR pathway, a tissue microarray of 50 chordoma cases was analysed for expression of active molecules involved in this signalling pathway by immunohistochemistry and a selected number by western blot analysis. Chordomas were positive for p-AKT (92%), p-TSC2 (96%), p-mTOR (27%), total mTOR (75%), p-p70S6K (62%), p-RPS6 (22%), p-4E-BP1 (96%) and eIF-4E (98%). Phosphatase and tensin homologue deleted on chromosome 10 expression was lost in 16% of cases. Mutations failed to be identified in PI3KCA and RHEB1 in the 23 cases for which genomic DNA was available. Fluorescence in situ hybridisation analysis for mTOR and RPS6 loci showed that 11 of 33 and 21 of 44 tumours had loss of one copy of the respective genes, results which correlated with the loss of the relevant total proteins. Fluorescence in situ hybridisation analysis for loci containing TSC1 and TSC2 revealed that all cases analysed harboured two copies of the respective genes. On the basis of p-mTOR and or p-p70S6K expression there is evidence indicating that 65% of the chordomas studied may be responsive to mTOR inhibitors, rapamycin or its analogues, and that patients may benefit from combined therapy including drugs that inhibit AKT.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Presneau N,Shalaby A,Idowu B,Gikas P,Cannon SR,Gout I,Diss T,Tirabosco R,Flanagan AMdoi
10.1038/sj.bjc.6605019subject
Has Abstractpub_date
2009-05-05 00:00:00pages
1406-14issue
9eissn
0007-0920issn
1532-1827pii
6605019journal_volume
100pub_type
杂志文章abstract：BACKGROUND:Tallness has consistently been associated with an increased risk of breast cancer. We investigated the association further by decomposing height into leg length and sitting height. METHODS:From the prospective Danish cohort 'Diet, Cancer and Health', 23 864 postmenopausal women enrolled during 1993-1997 wer...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.244
更新日期：2012-06-26 00:00:00
abstract：:Dipyridamole has been shown to enhance the in vitro activity of antimetabolite anticancer drugs through the inhibition of nucleoside transport. However, the clinical potential of dipyridamole has not been realized because of the avid binding of the drug to the plasma protein alpha1-acid glycoprotein (AGP). Dipyridamol...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690591
更新日期：1999-08-01 00:00:00
abstract：BACKGROUND:Pre-existing non-cancer conditions may complicate and delay colorectal cancer diagnosis. METHOD:Incident cases (aged ⩾40 years, 2007-2009) with colorectal cancer were identified in the Clinical Practice Research Datalink, UK. Diagnostic interval was defined as time from first symptomatic presentation of col...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2017.127
更新日期：2017-06-06 00:00:00
abstract：:Previous studies have reported the clinical usefulness of reverse transcription-polymerase chain reaction (RT-PCR) detection of thyroglobulin (TG) mRNA in the peripheral blood of patients with differentiated thyroid carcinoma. To evaluate this usefulness, we measured TG mRNA in the peripheral blood of patients diagnos...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.1904
更新日期：2001-07-06 00:00:00
abstract：:The tolerability, anti-tumour activity and pharmacokinetic interaction of high-dose intravenous cyclosporin combined with intravenous etoposide was evaluated in children. Eighteen patients with recurrent or refractory tumours, all of whom had previously received etoposide, were treated with a combination of high-dose ...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1998.383
更新日期：1998-06-01 00:00:00
abstract：:Photodynamic therapy (PDT) using Photofrin was used in combination with a hypoxic toxin (mitomycin C, MMC) to treat four patients with recurrent skin metastasis of a mammary carcinoma. In preclinical experiments an additive effect was found for the combination of MMC and PDT for treating subcutaneous RIF1 tumours in m...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.186
更新日期：1996-04-01 00:00:00
abstract：:Growth factor-induced migration is a rate-limiting step in tumour invasiveness. The molecules that regulate this cellular behaviour would represent novel targets for limiting tumour cell progression. Epidermal growth factor (EGF) receptor (EGFR)-mediated motility, present in both autocrine and paracrine modes in prost...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603234
更新日期：2006-07-17 00:00:00
abstract：:While statins have been highly effective for lowering serum cholesterol and reducing the incidence of coronary events, they have multiple other effects. Certain statins block the interaction of adhesion molecules that are important for cell-cell interactions including those between EBV-transformed B cells. These same ...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6602561
更新日期：2005-05-09 00:00:00
abstract：BACKGROUND:Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, incr...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.40
更新日期：2013-03-05 00:00:00
abstract：:This study reports on the frequency and disease association pattern of a number of gene rearrangements in a large panel of lymphoid tumours (n = 94). We detected the t(11;14) translocation, involving rearrangement of the BCL-1 locus, in 60% of mantle cell lymphomas. The BCL-2 gene, located at band 18q21, was rearrange...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.279
更新日期：1997-01-01 00:00:00
abstract：BACKGROUND:The clinical utility of machine-learning (ML) algorithms for breast cancer risk prediction and screening practices is unknown. We compared classification of lifetime breast cancer risk based on ML and the BOADICEA model. We explored the differences in risk classification and their clinical impact on screenin...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0937-0
更新日期：2020-09-01 00:00:00
abstract：:We studied 5555 seminoma patients and 3733 patients with nonseminomatous testicular cancers diagnosed in Southeast England between 1960 and 2004. For both groups survival improved over time: 10-year relative survival increased from 78% in 1960-1969 to 99% in 1990-2004 for seminomas, and from 55 to 95% for nonseminomas...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603589
更新日期：2007-02-12 00:00:00
abstract：:High expression of thymidylate synthase (TS) and inactivation of p53 are allegedly associated with chemoresistance. The authors evaluated TS and p53 expression in gastric cancer treated with neoadjuvant S-1/cisplatin chemotherapy. Paraffin sections of pretreatment biopsy and surgical specimens from 41 gastric cancers ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603546
更新日期：2007-01-29 00:00:00
abstract：BACKGROUND:Colorectal cancer (CRC) diagnoses and disease-specific survival (DSS) vary between ethnic groups in the United States. However, few studies have assessed differences among Asian subgroups. METHODS:The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with invasive CRC...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.97
更新日期：2013-04-16 00:00:00
abstract：BACKGROUND:Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) contains crucial information about tumour heterogeneity and the transport limitations that reduce drug efficacy. Mathematical modelling of drug delivery and cellular responsiveness based on underutilised DCE-MRI data has the unique potential to p...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605773
更新日期：2010-08-10 00:00:00
abstract：OBJECTIVE:Detection of lymph node involvement in women with IB2-IIB cervical cancer could have a positive effect on survival. We set out to evaluate the incidence of pelvic and/or para-aortic lymph node involvement using the sentinel node (SN) biopsy and its impact on survival. METHODS:From 2002 to 2010, 66 women with...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.541
更新日期：2012-01-03 00:00:00
abstract：:Eleven patients suffering from intra-abdominal malignancy were treated with various doses of intraperitoneal mitomycin C adsorbed onto activated carbon particles. Seven of the patients underwent resection of their primary gastric tumour and all developed potentially life-threatening severe complications that proved to...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.615
更新日期：1997-01-01 00:00:00
abstract：BACKGROUND:The purpose of this study was to evaluate the number of ovarian cancer and primary peritoneal cancer (PPC) progressive disease cases identified via routine follow-up procedures and the corresponding cost throughout a 16-year period at a single medical institution. METHODS:Previously undiagnosed epithelial o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605963
更新日期：2010-11-23 00:00:00
abstract：:Vascular endothelial growth factor (VEGF) is recognized to play a predominant role in breast cancer prognosis. The action of VEGF is mediated by two high-affinity receptors with ligand-stimulated tyrosine kinase activity: VEGFR-1/flt-1 and VEGFR-2/flk-1, which are expressed mainly in vascular endothelial cells. To the...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6692206
更新日期：1999-12-01 00:00:00
abstract：:A regional cancer network has been set up in the Rhône-Alpes region in France. The aim of the project is to improve the quality of care and to rationalize prescriptions in the network. In this network, we assessed the impact of the implementation of a clinical practice guidelines project by assessing the conformity of...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600057
更新日期：2002-02-01 00:00:00
abstract：BACKGROUND:Circulating total cytokeratin 18 (tCK18) and/or caspase cleaved cytokeratin 18 (cCK18) (measured by M65 and M30 enzyme-linked immunosorbent assays (ELISAs), respectively) are used as pharmacodynamic (PD) biomarkers of epithelial cell death in clinical trials. Having validated these ELISAs, we assessed their ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.416
更新日期：2012-10-23 00:00:00
abstract：:The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603685
更新日期：2007-04-23 00:00:00
abstract：:The role of high-risk human papillomavirus (hrHPV) testing in primary cervical screening has not been established. We generated a randomised evaluation design ultimately to clarify whether primary hrHPV testing implemented into routine screening can bring increase in the programme effectiveness. The aim of the present...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1038/sj.bjc.6602799
更新日期：2005-10-17 00:00:00
abstract：BACKGROUND:Oral squamous cell carcinoma (OSCC) has increased morbidity, and its high metastatic potential affects patient survival. Bromodomain containing 4 (BRD4) is a chromatin protein that associates with acetylated histone lysines and facilitates transcription. BRD4 has been implicated in cell proliferation, metast...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0907-6
更新日期：2020-08-01 00:00:00
abstract：:The tissue-specific translation elongation factor eEF1A2 is a potential oncogene that is overexpressed in human ovarian cancer. eEF1A2 is highly similar (98%) to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-alpha) making analysis with commercial antibodies difficult. We wanted to establish the express...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603748
更新日期：2007-05-21 00:00:00
abstract：:The level of Gross cell-surface antigen (GCSAa) expression at the surface of murine retrovirus-infected fibroblasts was determined by quantitative absorption of the anti-GCSAa activity of a serum produced in syngeneic W/Fu rats immunized against (C58NT)D lymphoma, and tested in a cytotoxicity assay against E male G2 l...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.97
更新日期：1981-05-01 00:00:00
abstract：:Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on th...
journal_title：British journal of cancer
pub_type： 杂志文章,实务指引
doi：10.1038/sj.bjc.6605642
更新日期：2010-05-25 00:00:00
abstract：:Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical chang...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603102
更新日期：2006-05-22 00:00:00
abstract：:We previously demonstrated a characteristically high sensitivity of pancreatic cancer cells to interferon alpha (IFN-alpha) gene transfer, which induced a more prominent growth suppression and cell death in pancreatic cancer cells than in other types of cancers and normal cells. The IFN-alpha protein can exhibit both ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602713
更新日期：2005-08-22 00:00:00
abstract：:Classification of lymphoid malignancy has changed markedly in recent years and advances have been made in therapy. This study investigated the variations in treatment and survival of 1622 patients in a population-based registry. A total of 1009 cases of malignant lymphoma (ML) were classified according to the Kiel cla...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.406
更新日期：1995-09-01 00:00:00
