Abstract:
BACKGROUND:In colorectal cancer (CRC), BRAF mutations influence tumour progression. In mismatch repair-deficient (dMMR) tumours, BRAF mutations are associated with a good prognosis, whereas in MMR-competent tumours, they are detrimental. The differential expression of the downstream MAPK pathway members, which are constitutively activated in BRAF mutant patients, may account for these differences. METHODS:Phosphorylation of ERK, p38MAPK and JNK was assessed by immunohistochemistry, utilising CRC tissue microarrays. A discovery cohort (n = 187) and a validation cohort (n = 801) were analysed for associations with BRAF mutations, clinicopathological characteristics and cancer-specific survival (CSS). RESULTS:In 801 CRC patients, nuclear ERK phosphorylation (HR 0.65 95% CI 0.48-0.88, p = 0.004) and the combined nuclear pERK/p-p38 score (HR 0.61 95% CI 0.45-0.82, p = 0.001) were independently associated with CSS, and were further associated with increased BRAF mutations (p = 0.003 and p = 0.002). When stratified for BRAF status, only MMR-competent patients harbouring the mutation and a strong combined nuclear pERK/p-p38 score (HR 0.49 95% CI 0.27-0.89, p = 0.016) demonstrated improved CSS. This improvement in CSS was specific to stage III CRC (HR 0.25 95% CI 0.10-0.64, p = 0.002). CONCLUSIONS:MMR-competent stage III tumours harbouring BRAF mutations have an improved prognosis when strong nuclear phosphorylation of both ERK and p38MAPK is present.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Roseweir AK,Halcrow ES,Chichilo S,Powell AG,McMillan DC,Horgan PG,Edwards Jdoi
10.1038/s41416-018-0174-ysubject
Has Abstractpub_date
2018-08-01 00:00:00pages
323-329issue
3eissn
0007-0920issn
1532-1827pii
10.1038/s41416-018-0174-yjournal_volume
119pub_type
杂志文章abstract::We have studied whether N-methylformamide can affect the expression pattern of adhesion molecules and the attachment behaviour of M14 human melanoma cells. The role of N-methylformamide on experimental and spontaneous pulmonary metastases from M14 cells in nude mice was also investigated. We demonstrate that N-methylf...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.35
更新日期:1998-01-01 00:00:00
abstract::To investigate possible relationships between genetic alterations and hormonal deregulation during breast cancer development and/or progression, we examined 616 primary breast cancers for loss of heterozygosity (LOH) at chromosomal regions 16q24, 17p13.3 and 17q21, and for amplifications of the ERBB2 and c-MYC loci. A...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.89
更新日期:1995-03-01 00:00:00
abstract::Protein kinases play a key role in intracellular signalling, participating at multiple levels along the transduction cascades that trigger mitogenic response. Because protein kinases are involved in mitogenic pathways, they are likely to play a role in the abnormal proliferation of malignant cells. In this study we co...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.675
更新日期:1998-11-01 00:00:00
abstract:BACKGROUND:Doxorubicin and cyclophosphamide (AC) therapy is an effective treatment for early-stage breast cancer. Doxorubicin is a substrate for ABCB1 and SLC22A16 transporters. Cyclophosphamide is a prodrug that requires oxidation to 4-hydroxycyclophosphamide, which yields a cytotoxic alkylating agent. The initial oxi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605587
更新日期:2010-03-16 00:00:00
abstract::Bcl-2 expression in colorectal carcinomas was studied in a series of 224 patients and the relation to p53 expression, stage and survival assessed. Bcl-2 expression was down-regulated compared with normal mucosa in 67% (151) of the cases. In 144 cases staining was positive for p53 (MAB DO7), and 41 of these 144 p53-pos...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.310
更新日期:1998-06-01 00:00:00
abstract::In a previous study we found that aromatic amines, particularly 4-aminobiphenyl, formed haemoglobin adducts at higher concentrations in the blood of smokers compared to non-smokers. We re-analyse here data on haemoglobin adducts of 14 aromatic amines in order to ascertain if the inter-individual variability left unexp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.120
更新日期:1990-04-01 00:00:00
abstract:BACKGROUND:This study aimed to evaluate the safety and efficacy of dose-dense weekly chemotherapy, followed by resection and/or thoracic radiotherapy. METHODS:Patients with histologically documented thymoma with unresectable stage III disease received 9 weeks of chemotherapy: cisplatin 25 mg m(-2) on weeks 1-9; vincri...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605731
更新日期:2010-06-29 00:00:00
abstract:BACKGROUND:Some components of the Mediterranean diet have favourable effects on endometrial cancer, and the Mediterranean diet as a whole has been shown to have a beneficial role on various neoplasms. METHODS:We analysed this issue pooling data from three case-control studies carried out between 1983 and 2006 in vario...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/bjc.2015.153
更新日期:2015-05-26 00:00:00
abstract:BACKGROUND:Cellular Dissociation Grade (CDG) composed of tumour budding and cell nest size has been shown to independently predict prognosis in pre-therapeutic biopsies and primary resections of oesophageal squamous cell carcinoma (ESCC). Here, we aimed to evaluate the prognostic impact of CDG in ESCC after neoadjuvant...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0623-2
更新日期:2019-12-01 00:00:00
abstract::Rhizoxin is a tubulin-binding anti-neoplastic agent which is active in a range of murine tumour models. The recommended schedule, of intravenous (i.v.) bolus administration at a dose of 2 mg m-2 every 3 weeks, has been assessed in three phase II trials of ovarian, renal and colorectal cancer. In general terms the drug...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1995.498
更新日期:1995-11-01 00:00:00
abstract:BACKGROUND:BRCAness is defined as shared tumour characteristics between sporadic and BRCA-mutated cancers. However, how to exactly measure BRCAness and its frequency in breast cancer is not known. Assays to establish BRCAness would be extremely valuable for the clinical management of these tumours. We assessed BRCAness...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.144
更新日期:2013-05-28 00:00:00
abstract::RNA tumour virus genes are contained in the chromosomal DNA of most vertebrates, and may be transmitted vertically from parent to progeny along with other cellular genes, as well as horizontally as infectious particles. Activation of these viral genes may be part of the means by which RNA tumour viruses produce cancer...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/bjc.1978.23
更新日期:1978-02-01 00:00:00
abstract::Benzo[b]thiophenesulphonamide 1,1-dioxide (BTS) derivatives are strong cytotoxic agents that induce reactive oxygen species (ROS) overproduction and apoptosis in tumour cells. Although the precise origin of BTS-induced ROS is not known, a clear correlation between their cytotoxic effect and ability to inhibit a tumour...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602383
更新日期:2005-02-28 00:00:00
abstract::Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients...
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.6602388
更新日期:2005-02-28 00:00:00
abstract::Chemotherapy has been regarded as standard therapy for the majority of women with advanced epithelial ovarian cancer for several decades, with this role filled largely by the alkylating agents - used as monotherapy - until the mid-1980s. The activity of cisplatin in this disorder was established during the 1970s, and ...
journal_title:British journal of cancer
pub_type: 历史文章,杂志文章,评审
doi:10.1038/sj.bjc.6601494
更新日期:2003-12-01 00:00:00
abstract::Eighty-two patients were randomly allocated to receive intravenous acyclovir 5 mg kg-1 t.d.s. for 23 days followed by oral acyclovir 800 mg 6-hourly for 6 months or matching placebos after allogeneic bone marrow transplantation. Herpes simplex and varicella zoster virus infections were significantly reduced during the...
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/bjc.1989.88
更新日期:1989-03-01 00:00:00
abstract::Neurofilaments (NFs) are specific intermediate filaments to neural cells. Mammalian NFs are protein triplets composed of three major subunits with respective molecular weights of approximately 70, 150 and 200 kD. Using an immunohistochemical method, 13 carcinoid tumours from different sites were examined for the prese...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.161
更新日期:1991-05-01 00:00:00
abstract::5'-nucleotidase activity, arachidonate metabolism and adenosine uptake were measured in P388 murine leukaemia cells and in a subline resistant to doxorubicin. These membranes related activities were found to be increased in the doxorubicin resistant cell line, compared to the drug sensitive cells. It is suggested that...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.71
更新日期:1984-04-01 00:00:00
abstract::The therapeutic efficacy of gemcitabine, a new nucleoside analogue, was assessed in a variety of well-established human soft tissue sarcoma and ovarian cancer xenografts grown s.c. in nude mice. Tumour lines selected had different histological subtypes, growth rates and sensitivities to conventional cytostatic agents....
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.285
更新日期:1993-07-01 00:00:00
abstract::This study evaluated the impact of province-wide treatment guidelines on consistency of adjuvant therapy for node-negative breast cancer. A retrospective population-based cohort study was conducted in the Canadian provinces of British Columbia, which has province-wide guidelines, and Ontario, which does not. All eligi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.262
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:This study is to investigate the effects of geserelin+tamoxifen (TAM) on estradiol level, breast density (BD), endometrial thickness (ET), and blood lipids in premenopausal and perimenopausal women with hormone receptor-positive early-stage breast cancer. METHODS:This study recruited 110 premenopausal and p...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/bjc.2013.324
更新日期:2013-08-06 00:00:00
abstract::The cytotoxicity of three platinum complexes, cis-diamminedichloroplatinum(II) (cis-platin), cis-dichloro-trans-dihydroxy-cis-bis (isopropylamine) platinum(IV), (CHIP) and diammine (1, 1-cyclobutane-dicarboxylato) platinum(II) (carboplatin) on Chinese Hamster ovary (CHO) and mouse sarcoma RIF-1 cells cultured in vitro...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.126
更新日期:1988-06-01 00:00:00
abstract::The RNASEL gene on chromosome 1q25 has been identified as a prostate cancer susceptibility gene. We screened for RNASEL germline mutations in familial prostate cancer patients, and performed a case-control study to examine the association of specific variants with prostate cancer risk in the Japanese. Three variants w...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601075
更新日期:2003-08-18 00:00:00
abstract::Although most colorectal cancer develops based on the adenoma-adenocarcinoma sequence, morphologically, colorectal cancer is not a homogeneous disease entity. Generally, there are two distinct morphological types: polypoid and ulcerative colorectal tumours. Previous studies have demonstrated that K-ras codon 12 mutati...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600214
更新日期:2002-04-08 00:00:00
abstract::The purpose of this study was to evaluate the occurrence of lymphatic drainage to non-axillary sentinel nodes and to determine the implications of this phenomenon. A total of 549 breast cancer patients underwent lymphoscintigraphy after intratumoural injection of (99m)Tc-nanocolloid. The sentinel node was intraoperati...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6600359
更新日期:2002-09-23 00:00:00
abstract:BACKGROUND:The community-based incidence of cancer treatment-related long-term consequences is uncertain. We sought to establish the burden of health outcomes that have been associated with treatment among British long-term cancer survivors. METHODS:We identified 26,213 adults from the General Practice Research Databa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.420
更新日期:2011-11-08 00:00:00
abstract::The continuous cell line UCRU BL 17CL was derived from a human invasive bladder cancer and expresses elements of transitional, squamous and glandular differentiation. Nine clones of this line were established by limit dilution and have been extensively characterised. Only six of these clones grew subcutaneously in nud...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.81
更新日期:1990-03-01 00:00:00
abstract:BACKGROUND:Bcl-xL has an important role in the control of cell death through its inhibition of apoptosis. The aim of this study was to investigate the clinicopathological significance of Bcl-xL in upper urinary tract urothelial carcinoma (UTUC) and the therapeutic effect of targeting Bcl-xL protein in urothelial carcin...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.216
更新日期:2013-06-11 00:00:00
abstract::Studies of families who segregate BRCA2 mutations have found that men who carry disease-associated mutations have an increased risk of prostate cancer, particularly early-onset disease. A study of sporadic prostate cancer in the UK reported a prevalence of 2.3% for protein-truncating BRCA2 mutations among patients dia...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603929
更新日期:2007-09-17 00:00:00
abstract::Regional lymph node metastasis is a very important prognostic indicator. In the metastatic process, reduction in cell to cell adhesion including E-cadherin-catenin cell adhesion complex is an essential step. We investigated immunohistochemical expression of E-cadherin, alpha-catenin and beta-catenin in 159 tissue samp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601124
更新日期:2003-08-04 00:00:00