Abstract：
:Caffeine has for many years been known to be involved in the sensitization of DNA to damage. One potential mechanism recently put forward is an override of the G2/M block induced by irradiation, which would leave the cells less time for DNA repair prior to mitosis. However, different cell types display a variety of responses and no clear pathway has yet emerged, especially as little is known about the capacity of this agent to enhance DNA damage in normal, untransformed cells. Continuous exposure to commonly used caffeine concentrations (1-5 mM) inhibited the proliferation of normal human fibroblasts (NHFs) in a dose-dependent manner to up to 80% at 5 mM. Exposure of exponentially growing NHFs to UVc radiation (20 J m(-2)) or gamma radiation (2.5-8 Gy) led to a 45-60% inhibition of proliferation and protracted accumulation of cells in the G2/M phase. Addition of 2 mM caffeine after irradiation induced slowing of the S phase passage, with a resultant delay in G2/M accumulation mimicking a G2/M block override. These results were confirmed by stathmokinetic studies, which showed delayed entry of the cells into mitosis in the presence of caffeine. Our data demonstrate that caffeine primarily inhibits replicative DNA synthesis and suggest that, at least in normal cells, caffeine potentiates the cytotoxicity of radiation by intervening in DNA repair rather than by overriding the G2/M block.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Deplanque G,Vincent F,Mah-Becherel MC,Cazenave JP,Bergerat JP,Klein-Soyer Cdoi
10.1054/bjoc.2000.1259subject
Has Abstractpub_date
2000-08-01 00:00:00pages
346-53issue
3eissn
0007-0920issn
1532-1827pii
S000709200091259Xjournal_volume
83pub_type
杂志文章abstract：:A total of 152 non-small cell lung cancers (NSCLC) were studied retrospectively to determine the relationship between epidermal growth factor receptor (EGF-R) status and the histological type, tumour size, nodal status and prognosis. EGF-R status was assessed on routinely embedded paraffin sections with an antibody to...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.156
更新日期：1989-05-01 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：:Data from the Oxford Survey have shown that childhood cancers are causes of in utero deaths which affect leukaemias more than solid tumours and difficult deliveries more than easy ones. As a result of these biases singletons give the impression of being more leukaemia-sensitive than twins. This is a false impression w...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1973.59
更新日期：1973-06-01 00:00:00
abstract：:In this study, the role of parity in conferring protection of the mammary gland against chemical carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) was investigated. Experiments were also carried out to determine if an 'interrupted' pregnancy was capable of reducing the incidence of mammary tumour inducti...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.88
更新日期：1988-04-01 00:00:00
abstract：:The family history of cancer in children treated for a solid malignant tumour in the Paediatric Oncology Department at Institute Gustave-Roussy, has been investigated. In order to determine the role of germline p53 mutations in genetic predisposition to childhood cancer, germline p53 mutations were sought in individua...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1167
更新日期：2000-06-01 00:00:00
abstract：BACKGROUND:When tumour tissue is unavailable, cell-free DNA (cfDNA)can serve as a surrogate for genetic analyses. Because mutated alleles in cfDNA are usually below 1%, next-generation sequencing (NGS)must be narrowed to target only clinically relevant genes. In this proof-of-concept study, we developed a panel to use ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2017.8
更新日期：2017-03-14 00:00:00
abstract：:Laminin-332 is major component of epithelial basement membrane, and has an important role in cell migration and tumour invasion. Recently, the phosphatidylinositol 3-kinase (PI3K) activation induced by laminin-332 during carcinogenesis or tumour invasion has been highlighted in skin squamous cell carcinoma. The expres...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604252
更新日期：2008-03-11 00:00:00
abstract：:Two meta-analyses were conducted to quantify the benefit of combining alpha-IFN to 5FU in advanced colorectal cancer in terms of tumour response and survival. Analyses were based on a total of 3254 individual patient data provided by principal investigators of each trial. The meta-analysis of 5FU +/- LV vs. 5FU +/- LV...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析
doi：10.1054/bjoc.2000.1669
更新日期：2001-03-02 00:00:00
abstract：:A cohort study was conducted to investigate the mortality of individuals employed by biological research institutes in the UK. The inclusion criteria were met by 12,703 individuals, of whom 95% were traced (11,502 alive, 395 deaths, 246 embarkations). All-cause mortality was significantly reduced in men (standardised)...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.221
更新日期：1996-05-01 00:00:00
abstract：:Expression of CDX2, a caudal-related homeobox gene, was found to be decreased in colorectal carcinomas. Heterozygous null mutant mice as to Cdx2 develop multiple intestinal adenomatous polyps. To clarify the role of CDX2 in colorectal carcinogenesis, we determined its genomic structure, and searched for mutations of C...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690068
更新日期：1999-02-01 00:00:00
abstract：BACKGROUND:Extracellular matrix (ECM) plays a crucial role in tumour behaviour. Prolyl-4-hydroxlase-A2 (P4HA2) is a key enzyme in ECM remodelling. This study aims to evaluate the prognostic significance of P4HA2 in breast ductal carcinoma in situ (DCIS). METHODS:P4HA2 expression was assessed immunohistochemically in m...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-018-0337-x
更新日期：2018-12-01 00:00:00
abstract：:In a longitudinal study of the evolution of serum beta 2-microglobulin (beta 2-m) levels in 37 patients with myelomatosis, those patients with a level of < 4 mg/l at first presentation had a median survival of 46 months, whereas those with an initial level of > mg/l had a median survival of 15 months. THe beta 2-m app...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1980.273
更新日期：1980-10-01 00:00:00
abstract：:Capecitabine is an oral prodrug of 5-fluorouracil (FU). Since FU concentrations achieved in malignant lesions are an important determinant of efficacy, we investigated the intratumoral transcapillary transfer of capecitabine and its metabolites in vivo. A total of 10 patients with skin metastases from breast cancer re...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600809
更新日期：2003-03-10 00:00:00
abstract：BACKGROUND:LGR5 is an important marker of intestinal stem cells and performs its vital functions at the cell membrane. Despite the importance of LGR5 to both normal and cancer stem cell biology, it is not known how microenvironmental stress affects the expression and subcellular distribution of the protein. METHODS:Nu...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.4
更新日期：2015-02-17 00:00:00
abstract：:MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as endogenous negative gene regulators. Dysfunctions of miRNAs are frequently found in malignancies, including lung cancer. In this review, we summarise the current understanding of miRNAs in lung cancer tumourigenesis, and highlight their potential in...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6605901
更新日期：2010-10-12 00:00:00
abstract：:Alternative splicing of survivin mRNA gives rise to multiple isoforms, that is, survivin and 3 splice variants, survivin-2B, survivin-3B and survivin-DeltaEx3. The aim of this study was to compare the expression of survivin, survivin-2B and survivin-DeltaEx3 in normal breast tissue, fibroadenomas, primary breast cance...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602314
更新日期：2005-01-17 00:00:00
abstract：BACKGROUND:Previous studies showed an increased risk of thyroid cancer among children and adolescents exposed to radioactive iodines released after the Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency, age at exposure and other factors on the dose-response are poorly understood. METHODS:...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605967
更新日期：2011-01-04 00:00:00
abstract：:Forty-two patients with clinical stage IIIA or IIIB breast cancer were treated with neoadjuvant chemotherapy followed by mastectomy and radiotherapy. The median follow-up was 32 months (range 10-72 months) and the median time to progression was 17 months (range 10-30 months). A multivariate analysis showed that a long...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.99
更新日期：1998-02-01 00:00:00
abstract：:From 1,211 breast cancers, 15 oestrogen receptor (ER) negative-progesterone receptor (PgR) positive breast cancers by conventional dextran coated charcoal steroid binding assays in cytosol were reassessed using Elisa techniques with monoclonal antireceptors antibodies in the cytosolic and nuclear fractions, and immuno...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.187
更新日期：1992-06-01 00:00:00
abstract：:Between 1980 and 1985, 914 patients with head and neck squamous cell carcinoma underwent lymph node dissection in our institution. The prognostic value of clinical factors has already been reported (Mamelle et al, 1994, Am J Surg 168: 494-498). We present here a comparison of biological characteristics of pharyngeal t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.320
更新日期：1998-06-01 00:00:00
abstract：:The genetic basis for the majority of early onset or non-syndromic "familial" colorectal cancer (CRC) is unknown. Attenuated APC phenotype is characterized by relatively few colonic polyps, early age at onset of colon cancer compared with the general population, and inactivating germline mutations within specific regi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.1959
更新日期：2001-08-17 00:00:00
abstract：:Melanoma is one of the most aggressive types of cancer and resection of the tumour prior to dissemination of tumour cells is still the most effective treatment. Therefore, early diagnosis of melanocytic lesions is important and identification of novel (molecular) markers would be helpful to improve diagnosis. Moreover...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602612
更新日期：2005-06-20 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：:The matrix metalloprotease MMP-9 localizes to tumour-associated macrophages in human ovarian cancer but little is known of its regulation. Co-culture of human ovarian cancer cells (PEO-1) and a monocytic cell line (THP-1) led to production of 92-kDa proMMP-9. PEO-1-conditioned medium (CM) also stimulated THP-1 cells o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.568
更新日期：1998-09-01 00:00:00
abstract：:To clarify the mechanism of acquired CDDP resistance in ovarian cancer, we compared the microsatellite instability (MSI) by the amplification of 10 microsatellite loci and immunohistochemical detection of hMSH2 and hMLH1 expression between the primary resected tumours and the secondary resected residual tumours after ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.2037
更新日期：2001-09-28 00:00:00
abstract：:This study was designed to evaluate new bone resorption and tumour markers as possible alternatives to serial plain radiographs for the assessment of response to treatment. Thirty-seven patients with newly diagnosed bone metastases from breast cancer, randomized to receive oral pamidronate or placebo tablets in additi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690506
更新日期：1999-04-01 00:00:00
abstract：:I.p. administration at several dose levels over periods of up to 12 weeks, or continuous i.v. infusion of high doses of misonidazole (MISO) for 15 h, produced no significant change in peripheral nerve conduction velocity (NCV) and did not prevent the normal increase in NCV as the animals matured from 12 to 24 weeks of...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1980.94
更新日期：1980-04-01 00:00:00
abstract：BACKGROUND:There remains uncertainty on the need for bone staging in men with intermediate-risk prostate cancer. Current guidelines do not use mpMRI-staging information and rely on historic pathology grading. METHODS:We investigated the ability of mpMRI and the new Grade Group system to better predict bone metastasis ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.353
更新日期：2016-11-22 00:00:00
abstract：BACKGROUND:Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethano...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.457
更新日期：2014-10-14 00:00:00
abstract：:The tumour suppressor gene p53 has been found to be mutated or inactivated at high frequency in several common human tumours. We have examined a series of exocrine pancreatic carcinomas for over-expression of mutant forms of p53 by immunohistochemistry with a panel of specific antibodies. We found immunodetectable p53...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.467
更新日期：1991-12-01 00:00:00
