Abstract:
BACKGROUND:Though p53 mutations are rare in ES, there is a strong indication that p53 mutant tumours form a particularly bad prognostic group. As such, novel treatment strategies are warranted that would specifically target and eradicate tumour cells containing mutant p53 in this subset of ES patients. METHODS:PRIMA-1(Met), also known as APR-246, is a small organic molecule that has been shown to restore tumour-suppressor function primarily to mutant p53 and also to induce cell death in various cancer types. In this study, we interrogated the ability of APR-246 to induce apoptosis and inhibit tumour growth in ES cells with different p53 mutations. RESULTS:APR-246 variably induced apoptosis, associated with Noxa, Puma or p21(WAF1) upregulation, in both mutant and wild-type p53 harbouring cells. The apoptosis-inducing capability of APR-246 was markedly reduced in ES cell lines transfected with p53 siRNA. Three ES cell lines established from the same patient at different stages of the disease and two cell lines of different patients with identical p53 mutations all exhibited different sensitivities to APR-246, indicating cellular context dependency. Comparative transcriptome analysis on the three cell lines established from the same patient identified differential expression levels of several TP53 and apoptosis-associated genes such as APOL6, PENK, PCDH7 and MST4 in the APR-246-sensitive cell line relative to the less APR-246-sensitive cell lines. CONCLUSION:This is the first study reporting the biological response of Ewing sarcoma cells to APR-246 exposure and shows gross variability in responses. Our study also proposes candidate genes whose expression might be associated with ES cells' sensitivity to APR-246. With APR-246 currently in early-phase clinical trials, our findings call for caution in considering it as a potential adjuvant to conventional ES-specific chemotherapeutics.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Aryee DN,Niedan S,Ban J,Schwentner R,Muehlbacher K,Kauer M,Kofler R,Kovar Hdoi
10.1038/bjc.2013.635subject
Has Abstractpub_date
2013-11-12 00:00:00pages
2696-704issue
10eissn
0007-0920issn
1532-1827pii
bjc2013635journal_volume
109pub_type
杂志文章abstract::A death certificate-based case-control study was conducted on 207 women aged 25-44 who died of bladder cancer in England and Wales in the period 1971-89 and 411 controls matched on sex, year of death and age at death. An odds ratio of 12.0 (95% CI 1.5-99.7) was found for women with a history of paraplegia. Four of the...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.269
更新日期:1994-07-01 00:00:00
abstract:BACKGROUND:Paired related homoeobox 1 (PRRX1) has been identified as a new epithelial-mesenchymal transition (EMT) inducer in breast cancer. However, the function of PRRX1 in colorectal cancer (CRC) has not been elucidated. METHODS:We utilised ectopic PRRX1-expressing cell lines to analyse the function of PRRX1 in CRC...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.339
更新日期:2013-07-23 00:00:00
abstract::Trends in long-term relative survival from breast cancer are examined for women diagnosed in England and Wales up to 2001, using both period and hybrid approaches. Large improvements in long-term survival are predicted. Women with breast cancer still experience persistent excess mortality up to at least 20 years after...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603668
更新日期:2007-04-10 00:00:00
abstract::In the present study we demonstrate that Aza-dC in combination with Amsacrine has major antileukaemic properties in patients who have not already received extensive Ara-C therapy. Eight out of 11 patients in their first relapse of acute leukaemia achieved complete remission. Cross resistance between Ara-C and Aza-dC w...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.258
更新日期:1991-07-01 00:00:00
abstract::SR 4233 (3-amino-1,2,4-benzotriazine 1,4-dioxide) is an anti-tumour agent that has a highly selective toxicity to hypoxic cells. In this study we delineate the role of several different bioreductive enzymes in the metabolism of SR 4233 by two tumour cell lines HT 1080 (human fibrosarcoma) and SCCVII (mouse carcinoma)....
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.59
更新日期:1993-02-01 00:00:00
abstract::It is known that interferon-gamma (IFN-gamma) is produced by activated T and NK lymphoid cells, mononuclear cells, and macrophage and dendritic cells. Our previous studies have shown that IFN-gamma-like immunoreactivity also appears in human adrenal cortical tumour and phaeochromocytoma. To investigate whether human t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603870
更新日期:2007-08-06 00:00:00
abstract::Microcolonies were obtained by culturing cells of two human osteosarcoma lines (OHS and KPDX) and one human melanoma line (WIX-c) for either 24 or 72 h. The microcolonies were treated with either alpha-particle radiation emitted by the 211At-labelled monoclonal antibody (MAb) TP-3 or external beam X-rays. Survival of ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.196
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:CXC chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) have important roles in promoting tumour growth and metastasis. Therefore, targeting CXCR4 could be a promising strategy for treatment of human cancer. METHODS:To achieve this goal, we developed a h...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.1
更新日期:2014-03-04 00:00:00
abstract::The incidence of adenocarcinoma of the oesophagus in British women is among the highest in the world. To investigate its aetiology, we conducted a multi-centre, population based case-control study in four regions in England and Scotland. We included 74 incident cases in women with histologically confirmed diagnoses of...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1054/bjoc.2000.1121
更新日期:2000-07-01 00:00:00
abstract::Time trends in therapeutic approaches and in the prognosis of colon cancer for patients aged 75 years and above have been investigated in comparison with corresponding trends for younger patients using a population-based series of 2089 colon cancer patients diagnosed between 1976 and 1990 in the Côte-d'Or area (478,00...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.492
更新日期:1997-01-01 00:00:00
abstract::We followed a population-based cohort of 5696 women, 32-38 years of age, by registry linkage with cytology and pathology registries during a mean follow-up time of 4.1 years to assess the importance for CIN2+ development of type-specific HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and ...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.bjc.6603843
更新日期:2007-07-02 00:00:00
abstract:BACKGROUND:Human polypyrimidine tract binding protein 3 (PTBP3) was first discovered in 1999 and has been well characterised as a differentiation regulator. However, its role in human cancer has rarely been reported. Our previous study revealed increased PTBP3 protein level in gastric cancer tissues. Downregulation of ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.32
更新日期:2017-03-28 00:00:00
abstract:BACKGROUND:To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). METHODS:Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 ...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2017.92
更新日期:2017-06-06 00:00:00
abstract::Isomerisation to all-trans-retinoic acid (ATRA) is widely accepted as the key mechanism underlying the favourable clinical properties of 13-cis-retinoic acid (13cisRA). As intracellular metabolism of ATRA by CYP26 may result in clinical resistance to 13cisRA, an increase in efficacy may be achieved through modulation ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603779
更新日期:2007-06-04 00:00:00
abstract::Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery, the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated. The value of T(pot) in predicting th...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/sj.bjc.6600119
更新日期:2002-02-12 00:00:00
abstract:BACKGROUND:Tumours are made up of a mixed population of different types of cells that include normal structures as well as ones associated with the malignancy, and there are multiple interactions between the malignant cells and the local microenvironment. These intercellular interactions, modulated by the microenvironm...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.517
更新日期:2012-01-03 00:00:00
abstract::A crude membrane fraction isolated from mouse tumour cells was treated with various chemicals. The effects on the immunogenicity of the membrane sample were tested in syngeneic mice for tumour protection, using a challenge dose of 10(5) viable tumour cells. Best protection was obtained after immunization of mice with ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.236
更新日期:1978-10-01 00:00:00
abstract::The objective of the study was to evaluate the effect of neoadjuvant chemotherapy on the survival of patients with oropharyngeal cancer. Patients with a squamous cell carcinoma of the oropharynx for whom curative radiotherapy or surgery was considered feasible were entered in a multicentric randomized trial comparing ...
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:10.1054/bjoc.2000.1512
更新日期:2000-12-01 00:00:00
abstract::One hundred and eighteen doctors who treat pulmonary neoplasms in Ontario were asked how they would wish to be treated if they had non-small cell lung cancer. Four different scenarios were given. The physicians were then asked if they would consent to take part as subjects in one or more clinical trials for which they...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1986.224
更新日期:1986-10-01 00:00:00
abstract::Apurinic/apyrimidinic (AP) sites in DNA are potentially lethal and mutagenic. They can arise spontaneously or following DNA damage from reactive oxygen species or alkylating agents, and they constitute a significant product of DNA damage following cellular exposure to ionizing radiation. The major AP endonuclease resp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690447
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:We used bleomycin, etoposide, cisplatin (BEP), the most effective regimen in the treatment of germ cell tumours (GCTs) and increased dose-density by using pegfilgrastim to shorten cycle length. Our aim was to assess safety and tolerability. METHODS:Sixteen male patients with intermediate or poor prognosis m...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.309
更新日期:2011-09-06 00:00:00
abstract::Immunoglobulins (Ig) and some complement components (C) were quantified in sera from patients with gastric carcinoma before surgery and at regular intervals during a 5-year follow-up. The preoperative concentrations of C1-INH and C4 were higher (P < 0.0005 and P < 0.005) and IgG lower (P < 0.0005) in 50 patients with ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.376
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND:Impaired drug transport is an important factor that reduces the efficacy of anticancer agents against pancreatic cancer. Here, we report a novel combination chemotherapy using gemcitabine (GEM) and internalised-RGD (iRGD) peptide, which enhances tumour-specific drug penetration by binding neuropilin-1 (NRP1)...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.49
更新日期:2014-03-18 00:00:00
abstract::Some cancer cells depend on the function of specific molecules for their growth, survival, and metastatic potential. Targeting of these critical molecules has arguably been the best therapy for cancer as demonstrated by the success of tamoxifen and trastuzumab in breast cancer. This review will evaluate the type I IGF...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6602963
更新日期:2006-02-27 00:00:00
abstract::In rapidly frozen livers from chickens affected with myeloblastosis and Marek's disease and from unaffected control birds there exists a strong correlation between catalase activity and catalase Electron Paramagnetic Resonance (EPR) signal intensities. The diseased chickens had activities and signals reduced to as lit...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.189
更新日期:1984-09-01 00:00:00
abstract::A prospective, consecutive study of the aetiology of treatment-associated diarrhoea was conducted in 25 patients with disseminated germ cell cancer treated with intensive chemotherapy. Clostridium difficile was isolated in 45% of the diarrhoea episodes, which makes this species the most important bacterial pathogen in...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.334
更新日期:1992-10-01 00:00:00
abstract::Cells of a patient with Turcot's syndrome and of her parents were evaluated for the presence of molecular alterations in the p53 and the Ki-ras gene. Deletions on chromosome 17p, overexpression and point mutations of the p53 gene as well as mutations of the Ki-ras gene were detected in primary and metastatic tumour bu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.379
更新日期:1993-09-01 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...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605957
更新日期:2010-11-23 00:00:00
abstract:BACKGROUND:Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after ant...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.564
更新日期:2013-10-29 00:00:00
abstract::Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.344
更新日期:1990-10-01 00:00:00