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 to a loss of NQO1 activity. Sequence analysis showed that this mutation was at position 609 of the NQO1 cDNA, conferring a proline to serine substitution at position 187 of the NQO1 enzyme. Using polymerase chain reaction (PCR) analysis, we have found that the H596 human non-small-cell lung cancer (NSCLC) cell line has elevated NQO1 mRNA, but no detectable enzyme activity. Sequencing of the coding region of NQO1 from the H596 cells showed the presence of the identical homozygous point mutation present in the BE cell line. Expression and purification of recombinant wild-type and mutant protein from E. coli showed that mutant protein could be detected using immunoblot analysis and had 2% of the enzymatic activity of the wild-type protein. PCR and Northern blot analysis showed moderate to low levels of expression of the correctly sized transcript in the mutant cells. Immunoblot analysis also revealed that recombinant mutant protein was immunoreactive; however, the mutant protein was not detected in the cytosol of either BE or H596 cells, suggesting that the mutant proteins were either not translated or were rapidly degraded. The absence of any detectable, active protein, therefore, appears to be responsible for the lack of NQO1 activity in cells homozygous for the mutation. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for the mutation at position 609 conducted on 90 human lung tissue samples (45 matched sets of tumour and uninvolved tissue) revealed a 7% incidence of individuals homozygous for the mutation, and 42% heterozygous for the mutation. These data suggest that the mutation at position 609 represents a polymorphism in an important xenobiotic metabolizing enzyme, which has implications for cancer therapy, chemoprevention and chemoprotection.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Traver RD,Siegel D,Beall HD,Phillips RM,Gibson NW,Franklin WA,Ross Ddoi
10.1038/bjc.1997.11subject
Has Abstractpub_date
1997-01-01 00:00:00pages
69-75issue
1eissn
0007-0920issn
1532-1827journal_volume
75pub_type
杂志文章abstract::This study describes the effects of the glucolipid synthase inhibitor P4, (DL-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol ), on various functional and phenotypic parameters of 5T33 murine myeloma cells. Cell recovery was reduced by >85% following incubation of the cells for 3 days in the presence of 4 mic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690792
更新日期:1999-11-01 00:00:00
abstract::The relationship between skin tumours in man and exposure to polyaromatic hydrocarbons has been studied in lathe operators exposed to cutting oils. Seven cases of scrotal cancer and 13 cases of senile keratosis and keratoacanthoma were observed. The risk varied as the 1.6th power of duration of exposure for cancer on ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.435
更新日期:1990-12-01 00:00:00
abstract::Advances in understanding the role of vascular endothelial growth factor (VEGF) in normal physiology are giving insight into the basis of adverse effects attributed to the use of VEGF inhibitors in clinical oncology. These effects are typically downstream consequences of suppression of cellular signalling pathways imp...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6603813
更新日期:2007-06-18 00:00:00
abstract::T-lymphocyte maturation associated protein, MAL, has been described as a tumour-suppressor gene with diagnostic value in colorectal and oesophageal cancers, and can be inactivated by promoter hypermethylation. The aim of this study was to analyse the prevalence of MAL promoter hypermethylation and the association with...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604777
更新日期:2008-12-02 00:00:00
abstract:BACKGROUND:The need to unfold the underlying mechanisms of lung cancer aggressiveness, the deadliest cancer in the world, is of prime importance. Because Fas-associated death domain protein (FADD) is the key adaptor molecule transmitting the apoptotic signal delivered by death receptors, we studied the presence and cor...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.196
更新日期:2012-06-05 00:00:00
abstract::The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor. In the present study, we investigated the role of met expression on the modulation of apoptosis in colorectal tumours. The gene expressions of c-met and the anti-apoptotic bcl-2 family, including bcl-2, bcl-x(L)and bcl-w...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1301
更新日期:2000-09-01 00:00:00
abstract:BACKGROUND:Among patients with cancer, prior research suggests that patients with mental illness may have reduced survival. The objective was to assess the impact of psychiatric utilisation (PU) prior to cancer diagnosis on survival outcomes. METHODS:All residents of Ontario diagnosed with one of the top 10 malignanci...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0390-0
更新日期:2019-04-01 00:00:00
abstract::Thymidine incorporation in vitro by remission lymphocytes from a total of 6 patients with acute myeloid leukaemia (AML) was measured following stimulation by autochthonous and allogeneic AML blasts and cell lines. The early peak response to autochthonous blasts in 2 of these patients (48-72 h) is consistent with the c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1976.81
更新日期:1976-05-01 00:00:00
abstract:BACKGROUND:We evaluated the association between smoking status and thyroid cancer risk and whether this association is mediated by body mass index (BMI) and thyroid-stimulating hormone (TSH). METHODS:We performed a cohort study of 96,855 Korean adults who were followed annually or biennially for a median of 5.9 years....
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0224-5
更新日期:2018-08-01 00:00:00
abstract::We studied 5555 seminoma patients and 3733 patients with nonseminomatous testicular cancers diagnosed in Southeast England between 1960 and 2004. For both groups survival improved over time: 10-year relative survival increased from 78% in 1960-1969 to 99% in 1990-2004 for seminomas, and from 55 to 95% for nonseminomas...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603589
更新日期:2007-02-12 00:00:00
abstract::Cisplatin is one of the most active cytotoxic agents in the treatment of testicular cancer, but its clinical use is associated with side-effects such as ototoxicity, neurotoxicity and nephrotoxicity. Long-term kidney damage from cisplatin particularly affects the proximal tubular apparatus and can be detected by incre...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.673
更新日期:1996-12-01 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:BACKGROUND:Tallness has consistently been associated with an increased risk of breast cancer. We investigated the association further by decomposing height into leg length and sitting height. METHODS:From the prospective Danish cohort 'Diet, Cancer and Health', 23 864 postmenopausal women enrolled during 1993-1997 wer...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.244
更新日期:2012-06-26 00:00:00
abstract::Rats were given a single dose of dimethylnitrosamine (DMN, 20 mg/kg body weight) alone or 42 or 60 hours after a non-lethal hepatotoxic dose of carbon tetrachloride (CC1(4)) and killed 12 months later. DMN alone produced no tumours in the kidney and a few in the liver, but when given 42 hours after CC1(4), tumours for...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1973.57
更新日期:1973-06-01 00:00:00
abstract::When L2C leukaemic B lymphocytes from guinea-pigs were incubated in vitro with antibody directed to their surface immunoglobulin (Ig), a rapid rise in intracellular adenosine 3':5'-phosphate (cyclic adenosine monophosphate, cAMP) was observed. Estimation of cAMP was by a protein-binding assay using bovine adrenal prot...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1979.77
更新日期:1979-04-01 00:00:00
abstract::Variants of the melanocortin-1 receptor (MC1R) gene have been linked to sun-sensitive skin types and hair colour, and may independently play a role in susceptibility to cutaneous melanoma. To assess the role of MC1R variants in uveal melanoma, we have analysed a cohort of 350 patients for the changes within the major ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601358
更新日期:2003-11-17 00:00:00
abstract::The present study set out to evaluate perceptions of risk, psychological morbidity and health behaviours in women with a family history of breast cancer who have attended genetic counselling and determine how these differ from general population risk women. Data were collected from 62 genetic counselees (cases) attend...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.387
更新日期:1996-08-01 00:00:00
abstract::Human primary thyroid follicular epithelial cells were transfected with a plasmid containing an origin-defective SV40 genome (SVori-) to produce several immortal cell lines. Two of the 10 cell lines analysed expressed specific features of thyroid epithelial function (iodide-trapping and thyroglobulin production). Thes...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.387
更新日期:1989-12-01 00:00:00
abstract:BACKGROUND:Body mass index (BMI) has been associated with the risk of oesophageal cancer. But the influence of BMI on postoperative complication and prognosis has always been controversial. METHODS:In total, 2031 consecutive patients who underwent oesophagectomy between 1998 and 2008 were classified according to Asian...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/bjc.2013.666
更新日期:2013-11-26 00:00:00
abstract:BACKGROUND:Previous studies have demonstrated that senescent cancer-associated fibroblasts (CAFs) derived from genetically unstable oral squamous cell carcinomas (GU-OSCC), unlike non-senescent CAFs from genetically stable carcinomas (GS-OSCC), promoted keratinocyte invasion in vitro in a paracrine manner. The mechanis...
journal_title:British journal of cancer
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abstract::Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modifi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600708
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abstract::Increases of individual beta tubulin isotypes in antimicrotubule drug resistant cell lines have been reported by several laboratories. We have previously described elevations in beta(III)and beta(IVa)isotypes in estramustine and paclitaxel resistant human prostate carcinoma cells. To investigate further the function o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.1956
更新日期:2001-09-01 00:00:00
abstract::Two policies of palliative thoracic radiotherapy for non-small-cell lung cancer have been compared in a randomised multicentre controlled trial. A total of 369 patients with inoperable, histologically or cytologically confirmed disease, too advanced for radical 'curative' radiotherapy, and with their main symptoms rel...
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.1991.62
更新日期:1991-02-01 00:00:00
abstract::The response of a transplantable rat fibrosarcoma, RIB(5), to a single injection of 100 mg/kg body weight of cyclophosphamide, 0·5, 1, 2 and 3 days after treatment, has been studied by means of a morphometric analysis of tumour sections and has been compared to the changes occurring in untreated tumours. The results s...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1973.9
更新日期:1973-01-01 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::Carcinoembryonic antigen-like substances in the urine of patients with bladder carcinoma and of healthy male subjects occur in a wide range of average molecular sizes. Some of these substances are glycoproteins giving reactions of antigenic identity with carcinoembryonic antigen (CEA) derived from colorectal carcinoma...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1974.93
更新日期:1974-06-01 00:00:00
abstract::Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal-epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protea...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603006
更新日期:2006-04-24 00:00:00
abstract::With few exceptions, the major limit to high-dose chemotherapeutic treatments is the severity and duration of drug-induced myelosuppression. We have recently developed a monoclonal antibody, MAD11, which reacts with the potent anti-tumour antibiotic doxorubicin and other anthracyclines. To protect directly pluripotent...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.117
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:Wnt-signalling has an important role in renal cancer and it is modulated by genistein in other cancers. Recently, microRNAs (miRNAs) have emerged as new regulators of gene expression. Thus, we focused on miRNAs to examine the regulatory mechanism of genistein on the Wnt-signalling pathway in renal cell carci...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.173
更新日期:2013-05-28 00:00:00
abstract::In this review, we discuss the recent identification in vivo of a population of CD11c+ cells exhibiting simultaneous expression of both endothelial and dendritic cell markers, termed vascular leukocytes (VLCs). VLCs are highly represented in human ovarian carcinomas and, depending on the milieu, can assemble into func...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6602476
更新日期:2005-04-11 00:00:00