Abstract:
:The cytotoxic mechanism of a conjugate of doxorubicin (DXR) and glutathione (GSH) via glutaraldehyde (GSH-DXR) was investigated using DXR-sensitive (AH66P) and -resistant (AH66DR) rat hepatoma cells. GSH-DXR accumulated in AH66DR cells as well as in AH66P cells without efflux by P-gp and exhibited the potent cytocidal activity against both cells compared with DXR. To examine whether thiol from GSH-DXR affected the expression of cytotoxicity, two conjugates of DXR, with modified peptides containing alanine or serine substituted for cysteine in GSH were prepared and their cytotoxicities determined. Substitution of these amino acids for cysteine resulted in an approximately two- to fourfold reduction in cytotoxic activity against both cell lines compared with the effect of GSH-DXR. Depletion of intracellular GSH by treatment of both cells with buthionine sulphoximine did not change the cytotoxic activity of DXR, BSA-DXR or GSH-DXR. By co-treating the cells with tributyltin acetate, an inhibitor of glutathione S-transferase (GST), and either DXR, BSA-DXR or GSH-DXR, the cytotoxicity was markedly increased. Interestingly, GSH-DXR showed non-competitive inhibition of GST activity and its IC50 value was 1.3 microM. These results suggested that the inhibition of GST activity by GSH-DXR must be an important contribution to the expression of potent cytotoxicity of the drug.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Asakura T,Ohkawa K,Takahashi N,Takada K,Inoue T,Yokoyama Sdoi
10.1038/bjc.1997.557subject
Has Abstractpub_date
1997-01-01 00:00:00pages
1333-7issue
10eissn
0007-0920issn
1532-1827journal_volume
76pub_type
杂志文章abstract::We examined the association of diet with insulin-like growth factors (IGF) in 344 disease-free men. Raised levels of IGF-I and/or its molar ratio with IGFBP-3 were associated with higher intakes of milk, dairy products, calcium, carbohydrate and polyunsaturated fat; lower levels with high vegetable consumption, partic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600946
更新日期:2003-06-02 00:00:00
abstract::The formation of cyclic AMP was studied in normal liver, subcutaneous hepatomas derived from MH1C1 cells, and premalignant liver and primary hepatomas induced by the carcinogens 2-acetylaminofluorene (AAF) and 4-dimethylamino-azobenzene (DAB). While only very slight effects of prostaglandins (PG) were seen in slices o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.281
更新日期:1978-12-01 00:00:00
abstract::Defects in the apoptotic system are likely to play a role in tumorigenesis. Pancreatic carcinoma cells are extremely resistant to apoptosis induction by chemotherapy suggesting that the apoptosis machinery is faulty. We investigated the integrity of the cytochrome c-dependent apoptotic apparatus in 10 human pancreatic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600171
更新日期:2002-03-18 00:00:00
abstract::Tamoxifen is the current therapy of choice for patients with oestrogen receptor positive breast cancer, and it is currently under evaluation as a prophylactic for women at high risk of developing the disease. However, tamoxifen is also known to induce proliferative changes in the endometrium increasing the risk of dev...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600157
更新日期:2002-03-04 00:00:00
abstract::Recently, we have found a high frequency of p53 gene mutations in human functional adrenal tumours. As the tumorigenesis is a multigene defect, we believe that other oncogenes may also be involved in the initiation or progression of adrenal tumours. Using the single-strand conformational polymorphism (SSCP) method, we...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.177
更新日期:1998-04-01 00:00:00
abstract::A monoclonal antibody recognizing the blood group H type 2 antigen has been obtained from a BALB/c mouse immunized with MCF-7 (human mammary carcinoma) cells. The specificity of this antibody (A46-B/B10, IgM, kappa) has been identified by haemagglutination tests, immunohistochemistry, binding inhibition studies, and a...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.187
更新日期:1988-08-01 00:00:00
abstract::The aim of this phase I study was to determine the maximum tolerated dose of a 3-h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-1 min every 4 weeks for up to six cycles and to evaluate any possible pharmacokinetic interaction. Twelve chemonaive patients with ovarian cancer were treated w...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1997.47
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:Impaired drug transport is an important factor that reduces the efficacy of anticancer agents against pancreatic cancer. Here, we report a novel combination chemotherapy using gemcitabine (GEM) and internalised-RGD (iRGD) peptide, which enhances tumour-specific drug penetration by binding neuropilin-1 (NRP1)...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.49
更新日期:2014-03-18 00:00:00
abstract::The topical carcinogenicity to mouse skin of smoke condensates obtained from a tobacco substitute (NSM), alone or in combination with tobacco, has been compared with condensate from tobacco and with acetone, the solvent used. Sixteen different types of cigarette were used to make the condensates, and the age-standardi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1977.47
更新日期:1977-03-01 00:00:00
abstract:BACKGROUND:The diagnosis of neuroendocrine neoplasms (NENs) is often delayed. This first UK population-based epidemiological study of NENs compares outcomes with non-NENs to identify any inequalities. METHODS:Age-standardised incidence rate (ASR), 1-year overall survival, hazard ratios and standardised mortality rates...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0606-3
更新日期:2019-11-01 00:00:00
abstract::Nineteen benign human breast tumours, from 19 premenopausal patients, were processed into slices and each tumour was individually cultured for 2 days in Medium 199. The effects of bovine insulin (5.0 microgram/ml) human placental lactogen (10.0 microgram/ml) and human growth hormone (10.0 microgram/ml) on 3H-thymidine...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.196
更新日期:1978-08-01 00:00:00
abstract::Human papillomavirus (HPV) is thought to cause some vulval squamous cell carcinomas (VSCC) by degrading p53 product. Evidence on whether HPV-negative VSCC results from p53 mutation is conflicting. We performed immunohistochemistry for p53 product on 52 cases of lone vulval intraepithelial neoplasia (VIN), 21 cases of ...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析,多中心研究
doi:10.1038/sj.bjc.6600677
更新日期:2003-01-27 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::Expression of the wild-type p53 gene has an important role in cell differentiation, maturation and apoptosis. Mutation of the p53 gene is associated with tumour development and mutant p53 can promote cell proliferation. Recently wild-type p53 has been demonstrated to exist in two conformational variants: one acting as...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.444
更新日期:1993-11-01 00:00:00
abstract::In the endeavour to develop a model for studying gene therapy of cancers associated with human papillomaviruses (HPVs), mouse cells were transformed with the HPV type 16 (HPV16) and activated H-ras oncogenes. This was done by cotransfection of plasmid p16HHMo, carrying the HPV16 E6/E7 oncogenes, and plasmid pEJ6.6, ca...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1615
更新日期:2001-02-02 00:00:00
abstract::The 5-year relative survival rates of women diagnosed with breast cancer between 1992 and 1994 were compared among the 99 Health Authorities (1999 boundaries) of England. Substantial variation, with evidence of geographical clustering was observed. Part of this variation was explained by differences in deprivation bet...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601812
更新日期:2004-06-01 00:00:00
abstract::Minisatellite DNA probes which can detect a large number of autosomal loci dispersed throughout the human genome were used to examine the constitutional and tumour DNA of 35 patients with a variety of cancers of which eight were of gastrointestinal origin. Somatic changes were seen in the tumour DNA in ten of the 35 c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.71
更新日期:1987-04-01 00:00:00
abstract::To evaluate whether green tea consumption provides protection against stomach cancer death, relative risks were calculated using Cox proportional hazards regression analysis in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600487
更新日期:2002-07-29 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::This report presents the results of a study into the effect of breast self-examination (BSE) in a large defined population within the City of Nottingham since 1979. We have examined the effect of breast self-examination in a group of patients invited to attend for education in BSE compared with a group of historical c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.294
更新日期:1989-09-01 00:00:00
abstract::Within a population-based cohort study, 40,708 men aged 45-79 years followed from 1998 to 2004. After adjusting for potential confounders, we observed a strong inverse linear association between total daily physical activity (PA) and death from cancer (n=1153). For each increment of 4 metabolic equivalent (MET)-h day(...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604354
更新日期:2008-06-03 00:00:00
abstract::Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6603494
更新日期:2007-02-12 00:00:00
abstract:BACKGROUND:MEK is activated in ∼40% colorectal cancer (CRC) and 20-30% non-small cell lung cancer (NSCLC). Selumetinib is a selective inhibitor of MEK1/2, which is currently in clinical development. METHODS:We evaluated the effects of selumetinib in vitro and in vivo in CRC and NSCLC cell lines to identify cancer cell...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.129
更新日期:2012-05-08 00:00:00
abstract::The presence of succinyl-coenzyme A: acetoacetate CoA--transferase (3-oxo acid-CoA transferase), an initiator of ketone body utilization in non-hepatic tissue was examined in a number of animal and human tumours of peripheral tissues. While enzyme levels in heart, kidney, lymphocytes and bladder were high, the tumours...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.38
更新日期:1983-02-01 00:00:00
abstract:BACKGROUND:Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the 'Warburg effect') and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targete...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.120
更新日期:2013-04-30 00:00:00
abstract::In a prospective cohort study in Denmark of 8736 randomly selected people, no evidence was found among 1011 subjects who developed cancer that self-reported stressful major life events had increased their risk for cancer. ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603471
更新日期:2006-12-04 00:00:00
abstract::In a clinical investigation of observed postoperative survival, 563 patients have been registered for primary surgical treatment of colorectal cancer since 1974. The potential prognostic factors examined within the first days of hospitalization for primary resection included age of the patients, operability, location ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.250
更新日期:1981-11-01 00:00:00
abstract::A recent study showed an association between a single base substitution, T-->C, in the promotor region of the CYP17 gene, the risk of breast cancer and age at menarche in Asian, African-American and Latino women from California and Hawaii. The C allele was associated with increased risk of breast cancer, significantly...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.340
更新日期:1998-06-01 00:00:00
abstract::Cytochrome P450 3A is a drug-metabolising enzyme activity due to CYP3A4 and CYP3A5 gene products, that is involved in the inactivation of anticancer drugs. This study analyses the potential of cytochrome P450 3A enzyme in human colorectal cancer to impact anticancer therapy with drugs that are cytochrome P450 3A subst...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600494
更新日期:2002-09-09 00:00:00
abstract::The natural history of 45 cases of smouldering leukaemia has been studied. Males and females were equally represented, with a median age of 60.5. The median survival of the whole group was only 20 months, but rare cases lived 10 years or longer. 38% developed acute leukaemia; the remainder usually died of the results ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1982.179
更新日期:1982-08-01 00:00:00