Abstract：
BACKGROUND:Topoisomerase I (Topo I) poisons (e.g., camptothecin (CPT)), used to treat cancer, cause DNA breaks that are most cytotoxic during S phase. PARP-1 promotes DNA repair and PARP inhibitors (PARPi) sensitise cells to Topo I poisons. We aimed to determine whether chemosensitisation is also S phase specific using rucaparib, a potent PARPi in advanced clinical evaluation. METHODS:The impact of rucaparib, on CPT-induced cytotoxicity was measured in human colon cancer (LoVo) and leukaemic (K562) cells in asynchronous and cell cycle phase-separated cultures. Topoisomerase I and PARP levels and activity and the effect of rucaparib on DNA single-strand breaks (SSBs), double-strand breaks (DSBs) and collapsed replication fork induction and repair were determined in cell cycle phase-separated cells. RESULTS:The cytotoxicity of CPT was greatest during S phase, partially attributable to high Topo I activity, and rucaparib preferentially sensitised S-phase cells. Rucaparib increased CPT-induced DNA SSBs in all phases of the cell cycle, and increased DSB and γH2AX foci in S and G2, with γH2AX foci being highest in S-phase cells. Repair of SSBs and DSBs was most rapid during S then G2 phases and was substantially hindered by rucaparib. CONCLUSIONS:Rucaparib preferentially sensitises S-phase cells by increasing the frequency of collapsed replication forks.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Znojek P,Willmore E,Curtin NJdoi
10.1038/bjc.2014.378subject
Has Abstractpub_date
2014-09-23 00:00:00pages
1319-26issue
7eissn
0007-0920issn
1532-1827pii
bjc2014378journal_volume
111pub_type
杂志文章abstract：BACKGROUND:Laboratory studies suggest a possible role of magnesium intake in colorectal carcinogenesis but epidemiological evidence is inconclusive. METHOD:We tested magnesium-colorectal cancer hypothesis in the Nurses' Health Study, in which 85 924 women free of cancer in 1980 were followed until June 2008. Cox propo...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.76
更新日期：2012-03-27 00:00:00
abstract：BACKGROUND:Dysplasia is a marker of cancer risk in Barrett's oesophagus (BO), but this risk is variable and diagnosis is subject to inter-observer variability. Cancer risk in BO is increased when chromosomal instability is present. Nucleotyping (NT) is a new method that uses high-resolution digital images of nuclei to ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.353
更新日期：2011-10-11 00:00:00
abstract：BACKGROUND:Factors related to early stimulation of the immune system (breastfeeding, proxies for exposure to infectious agents, normal delivery, and exposure to animals in early life) have been suggested to decrease the risk of childhood acute lymphoblastic leukaemia (ALL). METHODS:The national registry-based case-con...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.53
更新日期：2015-03-17 00:00:00
abstract：:This article was originally published under a standard license to Publish, but has now been made available under a CC BY license. The PDF and HTML versions of the paper have been modified accordingly.An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：British journal of cancer
pub_type： 已发布勘误
doi：10.1038/s41416-019-0534-2
更新日期：2019-10-01 00:00:00
abstract：:Cells from V79 multicell spheroids must be exposed to approximately 50 times more etoposide than exponentially growing monolayers in order to produce the same amount of cell killing. A part of this difference in sensitivity is readily explained by the decrease in growth fraction of large spheroids, and by the protecti...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.97
更新日期：1993-03-01 00:00:00
abstract：:Diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is currently based on phenotypical analysis of an expanded pedigree. Diagnostic guidelines ('Amsterdam criteria') proposed by the International Collaborative Group on HNPCC are often too stringent for use with small families. There is also the possibility...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.508
更新日期：1995-11-01 00:00:00
abstract：:Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal population of the human breast cancer cell line, MDA-MB-435S, were established by pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype is characterised by an ability to relocate to another surface following invasio...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602221
更新日期：2004-11-15 00:00:00
abstract：:The characteristics of 7 human melanoma cell lines were compared with those of the xenografts from which they were established. The ultrastructure, melanin content, isozyme pattern and chromosome numbers of the cell lines were closely similar to those of the corresponding xenografts. The different cell lines gave rise...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.276
更新日期：1981-12-01 00:00:00
abstract：:Using flow cytometry and immunocytochemistry, we investigated the reactivities of two different murine monoclonal antibodies (MAbs), MRK 16 and MRK 20, specific to adriamycin-resistant K562 cells (K562/ADM) with peripheral human mononuclear cells (MNC) (mainly blastic cells and lymphocytes) from 31 patients with leuka...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.309
更新日期：1989-10-01 00:00:00
abstract：BACKGROUND:Several microRNA (miRNA) molecules have emerged as important post-transcriptional regulators of tumour suppressor and oncogene expression. Ras association domain family member 1 (RASSF1) is a critical tumour suppressor that controls multiple aspects of cell proliferation such as cell cycle, cell division and...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2017.110
更新日期：2017-05-23 00:00:00
abstract：:Bacteriochlorin a (BCA) is a second-generation photosensitizer that is effective in tumour destruction upon illumination with light of a wavelength of 760 nm. Tissue penetration by light at this wavelength is greater compared with wavelengths at which commonly used photosensitizers are illuminated, making it possible ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.353
更新日期：1998-06-01 00:00:00
abstract：:Evidence in the literature suggests that hyperthermia (HT) or inhibitors of calmodulin can increase the sensitivity of rodent cells to bleomycin (BLM) by interfering with DNA repair functions. In an attempt to explore methods of improving the efficacy of thermochemotherapy we have investigated the individual and combi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.14
更新日期：1986-01-01 00:00:00
abstract：:Accumulation of mutations in tumour suppressor genes and oncogenes has been proposed to underlie the initiation and progression of sporadic colorectal cancer (CRC). Evidence is accumulating to suggest that the caudal homeobox gene CDX2 is implicated in the pathogenesis of CRC. The CDX2 transcription factor is expresse...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1544
更新日期：2001-01-01 00:00:00
abstract：:Oesopharyngeal brush (OPB) sampling with cytological analysis can yield exfoliated cells from asymptomatic tumours of the upper aero-digestive tract and the oesophagus. In this study, we compared cytological evaluation and molecular analysis for the detection of exfoliated cancer cells sampled with an OPB. A total of ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600953
更新日期：2003-06-02 00:00:00
abstract：:The ultrastructure of two lymphoblastoid cell lines derived from Marek's disease lymphomata has been studied. The cells varied from 5 to 12 mum in diameter and had large round or oval nuclei. A nucleolus was occasionally present and about 3% of cells showed projections of the nuclear envelope. The cytoplasm contained ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1975.2
更新日期：1975-01-01 00:00:00
abstract：BACKGROUND:The Mediterranean diet has been shown to have a beneficial role on various neoplasms, but data are scanty on pancreatic cancer. METHODS:We analysed data from two case-control studies conducted in Italy between 1983 and 2008, including 362 and 326 pancreatic cancer cases and 1552 and 652 hospital-controls, r...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.345
更新日期：2013-09-03 00:00:00
abstract：:P450 reductase (NADPH:cytochrome P450 reductase, EC 1.6.2.4) is known to be important in the reductive activation of the benzotriazene-di-N-oxide tirapazamine (SR 4233). Using a panel of six human breast adenocarcinoma cell lines we have examined the relationship between P450 reductase activity and sensitivity to tira...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.478
更新日期：1995-11-01 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: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
abstract：BACKGROUND:CYFRA 21-1 serves as biomarker in several epithelial malignancies. However, its role in pancreatic cancer (PC) has not yet been investigated. METHODS:Within a prospective single-centre study serial blood samples were collected from patients with confirmed advanced PC. Pre-treatment values and weekly measure...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.2013.158
更新日期：2013-04-30 00:00:00
abstract：:Nuclear polyploidization in the livers of CF-1 mice, exposed to dieldrin (0, 1, 5 and 10 ppm in the diet), was studied up to the median time of liver tumour development (ranging from 15 to 27 months) in the respective treatment groups. In untreated controls nuclear polyploidization is characterized by a linear increas...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.160
更新日期：1988-07-01 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：BACKGROUND:Tissue micro-arrays (TMAs) are increasingly used to generate data of the molecular phenotype of tumours in clinical epidemiology studies, such as studies of disease prognosis. However, TMA data are particularly prone to missingness. A variety of methods to deal with missing data are available. However, the v...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析
doi：10.1038/sj.bjc.6606078
更新日期：2011-02-15 00:00:00
abstract：:Sodium polyanethol sulphonate (SPS) when incorporated into rat erythrocyte lysate (REL) containing semi-solid agar medium at 1 mg ml-1. markedly enhanced colony formation by a number of anchorage-independent cell lines. REL usually needed to be included for the expression of SPS induced potentiation as in its absence ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1984.230
更新日期：1984-11-01 00:00:00
abstract：BACKGROUND:The distinct expression pattern of tumour-associated antigens (TAAs) might be a critical reason for the inefficacy of immunity-based treatments and heterogeneous postsurgical recovery in patients with solid tumours, including hepatocellular carcinoma (HCC). However, little is known about the clinical value o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.390
更新日期：2013-08-20 00:00:00
abstract：:Smoking, nutrition, parity and oral contraceptive use have been reported as major environmental risk factors for cervical cancer. After the discovery of the very strong link between human papillomavirus (HPV) infection and cervical cancer, it is unclear whether the association of these environmental factors with cervi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.1999.1100
更新日期：2000-04-01 00:00:00
abstract：:Small cell bronchial carcinoma (SCC) xenografts with differing sensitivity to cyclophosphamide (CY) were investigated using a variety of techniques. Two xenografts (HX78 and HX88) were relatively sensitive to CY, one xenograft (HX72) was inherently resistant to CY and a fourth xenograft (HX78Cy) was a CY induced resis...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1985.98
更新日期：1985-05-01 00:00:00
abstract：:Clonogenic survival of HeLa, Chinese hamster and HaK cells after treatment with a range of cisplatin concentrations and exposure times was determined and cellular platinum concentrations were measured by PIXE. It was demonstrated that cisplatin cytotoxicity of the three cell lines varied considerably as a function of ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.168
更新日期：1986-08-01 00:00:00
abstract：:Two techniques for growing colonies of human tumour cells in soft agar have been applied to cell suspensions derived from fresh tumour tissue from 48 patients. Colonies were obtained in 31 cases, with plating efficiencies between 0.01 and 15%. In 11 cases the plating efficiencies were 1% or above. There was evidence t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1978.165
更新日期：1978-07-01 00:00:00
abstract：:Thyroid carcinomas of an additional series of 34 children exposed to radioactive fall-out after the Chernobyl reactor accident were analysed for mutations in the H-, K- and N-RAS and the p53 gene. Allele-specific oligonucleotide hybridization, single-strand conformation polymorphism (SSCP) and direct sequencing did no...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.157
更新日期：1998-03-01 00:00:00
