Abstract：
BACKGROUND:Chromosomal instability (CIN) is a common trait of cancer characterised by the continuous gain and loss of chromosomes during mitosis. Excessive levels of CIN can suppress tumour growth, providing a possible therapeutic strategy. The Mps1/TTK kinase has been one of the prime targets to explore this concept, and indeed Mps1 inhibitors synergise with the spindle poison docetaxel in inhibiting the growth of tumours in mice. METHODS:To investigate how the combination of docetaxel and a Mps1 inhibitor (Cpd-5) promote tumour cell death, we treated mice transplanted with BRCA1-/-;TP53-/- mammary tumours with docetaxel and/or Cpd-5. The tumours were analysed regarding their histopathology, chromosome segregation errors, copy number variations and cell death to understand the mechanism of action of the drug combination. RESULTS:The enhanced efficacy of combining an Mps1 inhibitor with clinically relevant doses of docetaxel is associated with an increase in multipolar anaphases, aberrant nuclear morphologies and cell death. Tumours treated with docetaxel and Cpd-5 displayed more genomic deviations, indicating that chromosome stability is affected mostly in the combinatorial treatment. CONCLUSIONS:Our study shows that the synergy between taxanes and Mps1 inhibitors depends on increased errors in cell division, allowing further optimisation of this treatment regimen for cancer therapy.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Maia ARR,Linder S,Song JY,Vaarting C,Boon U,Pritchard CEJ,Velds A,Huijbers IJ,van Tellingen O,Jonkers J,Medema RHdoi
10.1038/s41416-018-0081-2subject
Has Abstractpub_date
2018-06-01 00:00:00pages
1586-1595issue
12eissn
0007-0920issn
1532-1827pii
10.1038/s41416-018-0081-2journal_volume
118pub_type
杂志文章abstract：:Data obtained from multiple sources indicate that no single mechanism can explain the resistance to chemotherapy exhibited by non-small cell lung carcinomas. The multi-factorial nature of drug resistance implies that the analysis of comprising expression profiles may predict drug resistance with higher accuracy than s...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600463
更新日期：2002-07-29 00:00:00
abstract：:Serial transplantation of an HCG-producing human testicular teratoma in immune-deprived mice is described. The xenografted tumour was compared to the tumour of origin in histology, immunohistochemistry (using an immune peroxidase technique to localize HCG) autoradiography, marker production and growth rate. It is conc...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.104
更新日期：1979-05-01 00:00:00
abstract：BACKGROUND:There is emerging evidence to suggest that the association between socioeconomic circumstances and colorectal cancer incidence has changed over recent decades. METHODS:We conducted a descriptive population-based study to describe the relationship between socioeconomic circumstances and the incidence of colo...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.149
更新日期：2011-05-24 00:00:00
abstract：:The aim of this study was to determine the dose-limiting toxicity (DLT) and establish the recommended dose for mitomycin C added every 3 weeks to the standard combination dose of capecitabine. Cohorts of at least three patients with pretreated gastrointestinal carcinoma received capecitabine 1000 mg m(-2) orally twice...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1038/sj.bjc.6602025
更新日期：2004-08-31 00:00:00
abstract：BACKGROUND:Operable non-small cell lung cancer (NSCLC) patients whose tumours have spread to regional or central lymph nodes at the time of diagnosis have dismal prognoses compared with those who have limited disease. The current TNM staging system for NSCLC poorly distinguishes patients with lymph-node metastases who ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.92
更新日期：2016-05-10 00:00:00
abstract：:Bryostatin 1 is a novel antitumour agent derived from Bugula neritina of the marine phylum Ectoprocta. Nineteen patients with advanced solid tumours were entered into a phase I study to evaluate the toxicity and biological effects of bryostatin 1. Bryostatin 1 was given as a one hour intravenous infusion at the beginn...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1993.352
更新日期：1993-08-01 00:00:00
abstract：:Patients affected by squamous cell carcinoma of the head and neck (HNSCC) show frequent occurrence of multiple cancers and widespread precancerous lesions in the mucosa of the upper respiratory tract, a phenomenon known as field cancerization. In this study, we investigated the role of genetic instability in the devel...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.644
更新日期：1998-11-01 00:00:00
abstract：BACKGROUND:We studied the biological significance of genes involved in a novel t(8;12)(p21.3;p13.31) reciprocal translocation identified in cervical squamous cell carcinoma (SCC) cells. METHODS:The rearranged genes were identified by breakpoint mapping, long-range PCR and sequencing. We investigated gene expression in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.301
更新日期：2012-08-07 00:00:00
abstract：:Oesophageal adenocarcinoma is believed to arise from metaplastic mucosa in the distal oesophagus, a condition also known as Barrett's oesophagus (BE). BE develops as a result of injury caused by refluxing gastric and duodenal contents and is associated with increased risk of malignant transformation. Matrix metallopro...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.1929
更新日期：2001-08-03 00:00:00
abstract：:We have established a novel ascites tumour model (MDA435/LCC6) from the oestrogen receptor-negative, invasive and metastatic MDA-MB-435 human breast cancer cell line. MDA435/LCC6 cells grow as both malignant ascites and solid tumours in vivo in nude mice and nude rats, with a tumour incidence of approximately 100%. Un...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.29
更新日期：1996-01-01 00:00:00
abstract：:Postoperative hyperplasia enhances experimental intestinal carcinogenesis, but the effects of nonsurgical adaptation are uncertain. The tropic and tumour-promoting potentials of moderate hypothermia were tested in two groups of male Sprague-Dawley rats housed at 10 degrees C for 30 weeks. One group (n = 10) received a...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1987.51
更新日期：1987-03-01 00:00:00
abstract：:Specimens of formalin-fixed, paraffin-embedded non-small-cell lung carcinomas (NSCLCs; n = 187) were analysed immunohistochemically for expression of cyclin A. The analysis was intended to determine whether cyclin A has additional prognostic value for predicting patients' survival and drug response. Of the 187 NSCLCs,...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.302
更新日期：1997-01-01 00:00:00
abstract：:Patients with advanced malignant disease show an apparent lesser degree of lymphocyte sensitization to cancer antigen when tested under standard conditions than do early cases. In the serum of cancer patients there is a lymphocyte response depressing factor whose titre rises as the neoplasm becomes more extensive. The...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1972.23
更新日期：1972-06-01 00:00:00
abstract：:Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitat...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603341
更新日期：2006-10-09 00:00:00
abstract：:Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990-2003. We compared incidence rates among new ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605024
更新日期：2009-05-05 00:00:00
abstract：:To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this se...
journal_title：British journal of cancer
pub_type： 杂志文章,随机对照试验
doi：10.1038/sj.bjc.6603265
更新日期：2006-08-07 00:00:00
abstract：:The relationship between history of schistosomiasis and bladder cancer risk was investigated using data from a case-control study conducted between January 1994 and July 1996 in Alexandria, Egypt. Cases were 190 subjects with incident, histologically confirmed invasive cancer of the bladder, and controls were 187 subj...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.197
更新日期：1998-04-01 00:00:00
abstract：:We investigated the relation between head and neck cancer risk and alcohol consumption in the NIH-AARP Diet and Health Study. During 2,203,500 person-years of follow-up, 611 men and 183 women developed head and neck cancer. With moderate drinking (up to one alcoholic drink per day) as the referent group, non-drinkers ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603713
更新日期：2007-05-07 00:00:00
abstract：BACKGROUND:This study explored the association between smoking and colorectal malignant carcinoma (CRC) in the Chinese population at the national level for the first time. METHODS:In the China Nationwide Retrospective Mortality Survey conducted during 1989-1991, 12,942 CRC cases among 1,136,336 all-cause deaths aged ≥...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.9
更新日期：2014-03-04 00:00:00
abstract：:On the basis of preclinical data suggesting the possibility of maximising the efficacy of 5-fluorouracil and cisplatin by interferon, a pilot clinical trial was initiated in recurrent and/or metastatic head and neck cancer. Thirty-four patients were treated with cisplatin at 100 mg m-2, followed by 5-fluorouracil at 1...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1994.72
更新日期：1994-02-01 00:00:00
abstract：:To improve our understanding of the relationship and possible associations between human papillomavirus (HPV) infection and the development of cervical malignancies, the presence of multiple types of HPV DNA sequences in cervical carcinoma was determined in Chinese citizens living in two different geographical locatio...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.375
更新日期：1994-10-01 00:00:00
abstract：BACKGROUND:Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This s...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.277
更新日期：2011-08-23 00:00:00
abstract：:Adenosine deaminase (EC 3.5.4.4, ADA) has been assayed in lymphocytes, granulocytes and erythrocytes from 45 patients with haematological malignancies. Activities were uniformly low in lymphocytes from patients with chronic lymphocytic leukaemia. Variable, but abnormal activities were frequently found in multiple myel...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1976.45
更新日期：1976-03-01 00:00:00
abstract：:In spite of the wide range of tumours successfully treated with 5-aminolevulinic acid mediated photodynamic therapy, the fact that 5-aminolevulinic acid has low lipid solubility, limits its clinical application. More lipophilic 5-aminolevulinic acid prodrugs and the use of liposomal carriers are two approaches aimed a...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600144
更新日期：2002-03-04 00:00:00
abstract：:Age distributions of parents at birth of patients registered in the National Wilms' Tumour Study were compared to those of the general population. An increasing incidence of sporadic Wilms' tumour with increasing paternal age was found, with a relative risk of 2.1 of tumour in children of fathers over 55 compared to c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.148
更新日期：1993-04-01 00:00:00
abstract：:Studies in animal tumour models of colorectal cancer suggest that F(ab')2 antibody fragments to carcinoembryonic antigen (CEA) labelled with iodine-131 give superior therapy compared with intact anti-CEA antibody. The purpose of this study was to investigate this hypothesis in patients. Ten patients received intact A5...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1994.338
更新日期：1994-09-01 00:00:00
abstract：:The cardiotoxicity of 5-fluorouracil (FU) was attributed to impurities present in the injected vials. One of these impurities was identified as fluoroacetaldehyde which is metabolised by isolated perfused rabbit hearts into fluoroacetate (FAC), a highly cardiotoxic compound. FAC was also detected in the urine of patie...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.227
更新日期：1992-07-01 00:00:00
abstract：:Cellular mechanisms that account for tumour osteolysis associated with Ewing's sarcoma are uncertain. Osteoclasts are marrow-derived multinucleated cells (MNCs) that effect tumour osteolysis. Osteoclasts are known to form from macrophages by both receptor activator for nuclear factor-kappaB (RANK) ligand (RANKL)-depen...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603774
更新日期：2007-06-04 00:00:00
abstract：:A late-gestation neonatal antigen (gamma foetal antigen; gamma-FA) immunologically and biochemically unrelated to murine alpha-foetoprotein, was identified in several spontaneous and carcinogen-induced sarcomas and hepatic carcinomas of the mouse and rat. An approximate mol. wt of 35,000 for gamma-FA from both foetus ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.173
更新日期：1979-08-01 00:00:00
abstract：BACKGROUND:Lithium accumulates in the colon and inhibits the enzyme GSK-3β that possesses anti-carcinogenic effects. We therefore examined the association between lithium use and colorectal cancer risk in a nationwide study. METHODS:We used the Danish Cancer Registry to identify all patients diagnosed with incident co...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.10
更新日期：2016-03-01 00:00:00
