Abstract：
BACKGROUND:Circulating total cytokeratin 18 (tCK18) and/or caspase cleaved cytokeratin 18 (cCK18) (measured by M65 and M30 enzyme-linked immunosorbent assays (ELISAs), respectively) are used as pharmacodynamic (PD) biomarkers of epithelial cell death in clinical trials. Having validated these ELISAs, we assessed their utility in colorectal cancer (CRC). METHODS:We applied the assays in several settings: 53 controls; 97 patients undergoing surgery and 74 patients with metastatic CRC undergoing chemotherapy (55 first line; 56 patients with repeated sampling through chemotherapy). Prognostic significance was evaluated using Kaplan-Meier life tables and Cox models; PD utility was assessed by analysis of repeated measures. RESULTS:Median cCK18 and tCK18 levels were elevated in patients with cancer (both P=0.0001), and among cancer patients, there were increasing trends from early to advanced stages (both P(trends)=0.0001). Increasing tCK18 predicted for reduced survival after surgery with curative intent (adjusted hazard ratio (HR) for doubling in concentration 1.77, 95% CI: 1.04, 3.01) and after first-line chemotherapy in metastatic disease (adjusted HR per doubling in concentration=1.78, 95% CI: 1.37, 2.30). In patients with progressive disease during chemotherapy, repeated sampling revealed profiles with high baselines and progressive upwardly increases after cycle 1. CONCLUSION:This study provides evidence for cytokeratin 18 (CK18) as a prognostic and PD biomarker in patients with CRC and supports continued deployment of circulating CK18 in biomarker-enhanced trials.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Greystoke A,Dean E,Saunders MP,Cummings J,Hughes A,Ranson M,Dive C,Renehan AGdoi
10.1038/bjc.2012.416subject
Has Abstractpub_date
2012-10-23 00:00:00pages
1518-24issue
9eissn
0007-0920issn
1532-1827pii
bjc2012416journal_volume
107pub_type
杂志文章abstract：:NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the r...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603414
更新日期：2006-11-06 00:00:00
abstract：:NAD(P)H:quinone oxidoreductase (NQO1, EC 1.6.99.2) is an obligate two-electron reductase that can either bioactivate or detoxify quinones and has been proposed to play an important role in chemoprevention. We have previously characterized a homozygous point mutation in the BE human colon carcinoma cell line that leads...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.11
更新日期：1997-01-01 00:00:00
abstract：:We evaluated the degree of tubular differentiation in 172 samples of invasive ductal breast cancer in order to determine numerical thresholds for histological breast cancer grading. The tubular differentiation in each sample was defined as the fraction of fields showing tubular differentiation (FTD). The analysis was ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1222
更新日期：2000-05-01 00:00:00
abstract：BACKGROUND:Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.423
更新日期：2017-02-14 00:00:00
abstract：BACKGROUND:Vascular endothelial growth factor (VEGF)-mediated angiogenesis mediates tumour growth and metastasis. Meningiomas are primarily benign, slow-growing, highly vascularised tumours. Aside from VEGF, there is little data on the function of major angiogenic proteins in meningiomas. METHODS:The VEGFA, platelet-d...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.459
更新日期：2012-11-06 00:00:00
abstract：BACKGROUND:Patients whose colorectal cancer is treated after an emergency admission tend to have late-stage cancer and a poor prognosis. We identified risk factors for an emergency admission by linking data from the National Bowel Cancer Audit (NBCA) and the English Hospital Episode Statistics (HES), an administrative ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.300
更新日期：2014-07-29 00:00:00
abstract：:When assessing the value of a particular treatment, it is important to consider the impact it may have on the quality of life of those being treated. This is particularly so for cancer patients, whose life expectancy may be short. Patients with advanced colorectal cancer who participated in two international comparati...
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/bjc.1998.420
更新日期：1998-01-01 00:00:00
abstract：:Immunoreactive and bioassayable plasma fibronectin (opsonic α(2) surface-binding (SB) glycoprotein) was measured during experimental Sarcoma-180 tumour growth in mice. Male C57BL/6 mice were challenged s.c. with 2 × 10(6) viable Sarcoma-180 tumour cells and evaluated sequentially in parallel with saline-injected contr...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1980.174
更新日期：1980-06-01 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：:Pancreatic cancer is characterised by a hallmark desmoplastic response that includes upregulated expression of the extracellular matrix, and type I collagen in particular. Recent studies indicate that pancreatic cancer cells stimulate type I collagen synthesis in adjacent stellate cells, and that this upregulated type...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603088
更新日期：2006-05-08 00:00:00
abstract：:Limb-sparing surgeries have been performed more frequently than amputation based on the belief that limb-sparing surgeries provide improved function and quality-of-life (QOL). However, this has not been extensively studied in the paediatric population, which has unique characteristics that have implications for functi...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/sj.bjc.6602220
更新日期：2004-11-29 00:00:00
abstract：:Tumorigenic mouse lung-derived type 2 cell lines have large reductions in both beta-adrenergic-stimulated cAMP production and ligand binding to beta-adrenergic receptors. These tumorigenic cells are also relatively insensitive to glucocorticoids. Because glucocorticoids regulate both beta-adrenergic receptor expressio...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.377
更新日期：1996-08-01 00:00:00
abstract：:Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increa...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1054/bjoc.2001.1748
更新日期：2001-04-01 00:00:00
abstract：:Eleven patients with measurable subcutaneous or pulmonary metastases were selected for a study of the effectiveness of the radiosensitizer misonidazole (MIS). Evaluable data were obtained in 6 patients and radiosensitization demonstrated in 5. Patients were irradiated either before or after MIS, and each patient acted...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.281
更新日期：1979-12-01 00:00:00
abstract：:In this study we investigated the tumorigenicity, growth pattern and spontaneous metastatic ability of a series of nine human colorectal carcinoma cell lines after subcutaneous and intracaecal xenografting in nude mice. CaCo2 cells were found to be poorly tumorigenic to non-tumorigenic in either site; the other cell l...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.55
更新日期：1995-02-01 00:00:00
abstract：BACKGROUND:Currently, none of the available colorectal adenocarcinoma (CAC) testing has been established as a well-accepted diagnosis tool, particularly for the early stage of CAC. The recent discovery of serum microRNA (miRNA) profile has provided a new auxiliary approach for tumour diagnosis. Our study is involved in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.489
更新日期：2014-11-11 00:00:00
abstract：:The role of the anti-apoptotic protein Bcl-2 in lung cancer remains controversial. In order to clarify its impact on survival in small and non-small cell lung cancer (NSCLC), we performed a systematic review of the literature. Trials were selected for further analysis if they provided an independent assessment of Bcl-...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析,评审
doi：10.1038/sj.bjc.6601095
更新日期：2003-07-07 00:00:00
abstract：:In Vaud, Switzerland, the incidence of carcinoids based on 218 malignant and 215 benign cases rose from 19.6/10(6)in 1974-85 to 28. 2/10(6)in 1986-97, more so among males and malignant neoplasms. Lung was the commonest site for malignant and large intestine for benign carcinoids. Sixty-eight (16%) carcinoids had anoth...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1394
更新日期：2000-10-01 00:00:00
abstract：BACKGROUND:Uncertainty remains about the associations of adiposity with intestinal cancer in China and by its anatomical subtype. METHODS:The prospective China Kadoorie Biobank recorded 3024 incident cases of colorectal (CRC) and 143 cases of small intestine (SIC) cancer during a 10-year follow-up among 509 568 partic...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-018-0124-8
更新日期：2018-07-01 00:00:00
abstract：:The vascular architecture of four different tumour cell lines (CaX, CaNT, SaS, HEC-1B) transplanted subcutaneously in mice was examined by means of microvascular corrosion casting in order to determine whether there is a characteristic vascular pattern for different tumour types and whether it differs significantly fr...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690416
更新日期：1999-05-01 00:00:00
abstract：: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/s41416-020-0879-6
更新日期：2020-08-01 00:00:00
abstract：:Previous studies have shown that multidrug resistance (MDR) in the doxorubicin-selected lung tumour cell lines COR-L23/R, GLC4/ADR and MOR/R is associated with overexpression of the MRP gene. In this study we report that resistance to daunorubicin, vincristine and rhodamine 123 can be partially reversed in these cell ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.281
更新日期：1995-07-01 00:00:00
abstract：:Flow cytometric (FCM) estimation of DNA content has been performed on tumour tissue from 197 patients with high and intermediate grade non-Hodgkin's lymphoma (NHL) to investigate the clinicopathological correlations and prognostic significance of DNA ploidy and proliferative activity. Fifty-one per cent of tumours wer...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.388
更新日期：1989-12-01 00:00:00
abstract：:In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1580
更新日期：2001-05-18 00:00:00
abstract：:In a population-based prospective study of 19,998 Japanese individuals, consumption of vegetables, green-yellow and green leafy vegetables was inversely associated with the risk of hepatocellular carcinoma (101 cases), with multivariable hazard ratios for the highest vs lowest tertile of 0.61 (95% confidence interval ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604843
更新日期：2009-01-13 00:00:00
abstract：:It is suggested that the proximate carcinogenic forms of dialkylnitrosamines are their oxidation products, which retain the alkylnitrosamino moiety, but have acquired a carbonyl function as a result of omega or beta oxidation of an alkyl group. Such metabolites resemble the locally acting carcinogenic "nitrosamides" a...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1973.169
更新日期：1973-11-01 00:00:00
abstract：:The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690008
更新日期：1999-01-01 00:00:00
abstract：BACKGROUND:Hypoxia can activate autophagy, a self-digest adaptive process that maintains cell turnover. Mammalian target of rapamycin (mTOR) inhibitors are used to treat cancer but also stimulate autophagy. METHODS:Human mammary cancer cells and derived xenografts were used to examine whether hypoxia could exacerbate ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.644
更新日期：2013-11-12 00:00:00
abstract：:Disseminating disease is a predictive and prognostic indicator of poor outcome in children with neuroblastoma. Its accurate and sensitive assessment can facilitate optimal treatment decisions. The International Neuroblastoma Risk Group (INRG) Task Force has defined standardised methods for the determination of minimal...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究,实务指引
doi：10.1038/sj.bjc.6605029
更新日期：2009-05-19 00:00:00
abstract：:Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and th...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602420
更新日期：2005-03-14 00:00:00
