Abstract:
:The cellular pharmacology of a series of C8-linked pyrrolobenzodiazepine dimers with polymethylene linkers of n = 3-6 (compounds 1-4) has been studied in a range of human tumour cell lines. The four compounds showed the same pattern of relative activity in five ovarian carcinoma cell lines and one cervical carcinoma cell line with the order of IC50 values of 1 < or = 3 < 4 < 2, which correlated with the previously demonstrated DNA interstrand cross-linking ability of the compounds in plasmid DNA. In human leukaemic K562 cells the agents produced a block in the G2/M phase of the cell cycle characteristic of cross-linking drugs, and extensive interstrand cross-linking was observed in cells by alkaline elution with no evidence of single-strand breaks. Cross-links continued to increase up to 24 h following a 1 h exposure to drug, and no repair was evident by 48 h. In a series of ovarian and cervical carcinoma cell lines with acquired resistance to cisplatin no cross-resistance to the most potent compound 1 was observed in two lines whose major mechanism of resistance to cisplatin was reduced platinum transport. Cross-resistance to 1 was observed in a cell line (A2780cisR) possessing elevated glutathione, and depletion of intracellular glutathione using D,L-buthionine-S,R-sulphoximine (BSO) from 10.25 nmol to 2.8 nmol 10(-6) cells reduced the level of resistance from 11-fold to 2-fold compared with sensitive cells. Cross-linking in the resistant cells was restored to 80% of the level in the parent line by BSO pretreatment. There was also a correlation between glutathione levels and sensitivity to 1 measured in several other ovarian cell lines. Compound 1 also showed cross-resistance in the doxorubicin-resistant cell line 41MdoxR and partial cross-resistance in CH1doxR cells. Both these lines possess elevated levels of p170 glycoprotein. Following treatment with 6 microM verapamil, the resistance in these lines decreased almost 2-fold and 8-fold respectively.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Smellie M,Kelland LR,Thurston DE,Souhami RL,Hartley JAdoi
10.1038/bjc.1994.248subject
Has Abstractpub_date
1994-07-01 00:00:00pages
48-53issue
1eissn
0007-0920issn
1532-1827journal_volume
70pub_type
杂志文章abstract::The objective of this study was to prospectively measure peri-diagnostic and surgical time intervals for patients with suspected colorectal, lung, or prostate cancer. Prospective eligible patients were referred to a regional hospital in Ottawa, Canada between February 2004 and February 2005 for diagnostic assessment o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604819
更新日期:2009-01-13 00:00:00
abstract::Imatinib mesilate (Glivec), Novartis Pharmaceuticals) is a novel therapy for the treatment of chronic myeloid leukaemia (CML). We evaluated the cost-effectiveness of imatinib (600 mg daily) when used for the treatment of patients in advanced stages of CML (accelerated phase and blast crisis) against conventional thera...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601151
更新日期:2003-08-18 00:00:00
abstract::The tolerability, anti-tumour activity and pharmacokinetic interaction of high-dose intravenous cyclosporin combined with intravenous etoposide was evaluated in children. Eighteen patients with recurrent or refractory tumours, all of whom had previously received etoposide, were treated with a combination of high-dose ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1998.383
更新日期:1998-06-01 00:00:00
abstract::Postoperative hyperplasia enhances experimental intestinal carcinogenesis, but the effects of nonsurgical adaptation are uncertain. The tropic and tumour-promoting potentials of moderate hypothermia were tested in two groups of male Sprague-Dawley rats housed at 10 degrees C for 30 weeks. One group (n = 10) received a...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.51
更新日期:1987-03-01 00:00:00
abstract:BACKGROUND:Few studies have investigated the relationship between physician and patient-assessed performance status (PS) in blood cancers. METHODS:Retrospective analysis among 1418 patients with haematologic malignancies seen at Dana-Farber Cancer Institute between 2007 and 2014. We analysed physician-patient agreemen...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.260
更新日期:2016-09-27 00:00:00
abstract::Epithelial cadherin (E-CD) is a member of the cadherin family of cell adhesion molecules and has been implicated as an invasion suppressor molecule in vitro and in vivo. We analysed 174 breast tumours from the Nottingham/Tenovus Breast Cancer Series immunohistochemically for E-CD expression using the mouse monoclonal ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2178
更新日期:2001-12-14 00:00:00
abstract:BACKGROUND:Lymph node metastasis is one of the most important adverse prognostic factors for pancreatic cancer. The aim of this study was to identify novel lymphatic metastasis-associated markers and therapeutic targets for pancreatic cancer. METHODS:DNA microarray study was carried out to identify genes differentiall...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.37
更新日期:2011-03-15 00:00:00
abstract:BACKGROUND:Tumoural interstitial hypertension, possibly modulated by platelet-derived and vascular endothelial growth factor receptors (PDGFR and VEGFR), may mediate resistance to chemotherapy. METHODS:Forty-eight patients with advanced solid tumours received oral PDGFR inhibitor CP-868,596 (60-100 mg twice daily (BID...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.bjc.6605941
更新日期:2010-11-09 00:00:00
abstract::KRN 8602 (MX2) is a novel morpholino anthracycline derivative having the chemical structure 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. To investigate the mechanisms of resistance to MX2, we established an MX2-resistant phenotype (K562/MX2) of the human myelogeneous leukaemia cell line (K56...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602498
更新日期:2005-04-25 00:00:00
abstract:BACKGROUND:Little is known about the effect of participating in a colorectal cancer (CRC) screening programme on quality of life (QOL), neither for participants with a negative nor for those with a positive test result. These findings, however, are important to evaluate the impact of CRC screening. METHODS:Participant...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.386
更新日期:2012-10-09 00:00:00
abstract::Tumour recurrence and metastases of hepatocellular carcinoma (HCC) after hepatectomy are the major obstacles of long-term survival. The present study investigated the clinicopathological significance of a possible metastasis regulator Six1 in HCC patients who were undergone hepatectomy. Seventy-two pairs of RNA and 10...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603399
更新日期:2006-10-23 00:00:00
abstract::The last 15 years has seen an explosion of interest in the cancer stem cell (CSC). Although it was initially believed that only a rare population of stem cells are able to undergo self-renewing divisions and differentiate to form all populations within a malignancy, a recent work has shown that these cells may not be ...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6605821
更新日期:2010-08-10 00:00:00
abstract::It has been postulated that paternal gonadal exposure would increase the sex ratio by inducing X-chromosomal dominant lethals but that maternal gonadal exposure would decrease the sex ratio by inducing recessive sex-linked lethals. We therefore evaluated the sex ratio (male-to-female ratio) of children born to survivo...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600748
更新日期:2003-02-10 00:00:00
abstract::Although the presence of axillary node metastases in breast cancer is a key prognostic indicator and may influence treatment decisions, a significant proportion of patients diagnosed as axillary node negative (ANN) using standard histopathological techniques may have occult nodal metastases (OMs). A combination of lim...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.16
更新日期:1996-01-01 00:00:00
abstract::A cytofluorometric assay allowing the measurement of thymidine phosphorylation in single cells had been established (Hengstschläger & Wawra, 1993). This assay enables us to correlate intracellular thymidine kinase (TK) activity with the DNA content of single cells. Enzyme activity levels from neuroblastoma cells and n...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.187
更新日期:1993-05-01 00:00:00
abstract:BACKGROUND:Neuroblastoma is the most common malignancy of infancy but little is known about the aetiological factors associated with the development of this tumour. A number of epidemiological studies have previously examined the risk associated with paternal occupational exposures but most have involved small numbers ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605504
更新日期:2010-02-02 00:00:00
abstract:BACKGROUND:Gastroesophageal adenocarcinoma (GOA) has poor clinical outcomes and lacks reliable blood markers. Here we present circulating tumour DNA (ctDNA) as an emerging biomarker. METHODS:Forty patients (17 palliative and 23 curative) were followed by serial plasma monitoring. Primary tumour DNA was analysed by tar...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-1002-8
更新日期:2020-10-01 00:00:00
abstract:BACKGROUND:Efficacy and safety are the two considerations when characterising the effects of a new therapy. We sought to apply an innovative method of assessing the benefit-risk balance using data from a completed randomised controlled trial that compared erlotinib vs placebo added to gemcitabine in patients with advan...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/bjc.2015.55
更新日期:2015-03-17 00:00:00
abstract::Epidermal growth factor receptor (EGFR) gene mutations and increased copy numbers are considered as predictors of response to EGFR tyrosine kinase inhibitors (EGFR-TKI) in non-small-cell lung cancer (NSCLC). Lung cancer diagnosis is often based on cytology alone. However, almost all published data on EGFR gene analyse...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604142
更新日期:2008-01-15 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1973.45
更新日期:1973-05-01 00:00:00
abstract::Supplementary Table 1 and the Supplementary Figure legends were not included when this manuscript was first published. The files are now available here. ...
journal_title:British journal of cancer
pub_type: 已发布勘误
doi:10.1038/s41416-018-0130-x
更新日期:2018-08-01 00:00:00
abstract::Although most colorectal cancer develops based on the adenoma-adenocarcinoma sequence, morphologically, colorectal cancer is not a homogeneous disease entity. Generally, there are two distinct morphological types: polypoid and ulcerative colorectal tumours. Previous studies have demonstrated that K-ras codon 12 mutati...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600214
更新日期:2002-04-08 00:00:00
abstract::In 101 breast cancer patients, measurement of oestrogen receptor status in multiple biopsies across a tumour reveals a highly significant difference in the proportion of patients remaining either disease-free (P less than 0.04) or alive (P less than 0.005), when those with uniformly receptor positive (++) primary tumo...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.129
更新日期:1989-04-01 00:00:00
abstract::We evaluated the myelotoxicity and the anti-tumor potential of tallimustine, three of its analogues and carzelesin, with melphalan as reference substance. Tallimustine was tested by clonogenic assays on both human bone marrow (BM) and cord blood (hCB) cells, the other compounds on hCB only. The degree of inhibition of...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.155
更新日期:1997-01-01 00:00:00
abstract::Eleven groups of workers submitted a total of 21 bronchial tumour-associated antigen preparations and 19 antisera for comparative studies. Many of the antisera proved to be polyspecific despite absorption procedures. Most of the antigen preparations contained some material reactive towards a reference antiserum to nor...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.216
更新日期:1981-10-01 00:00:00
abstract::The tumour suppressor gene CDKN2A, located on chromosome 9p21, encodes the cell cycle regulatory protein p16. Inactivation of the CDKN2A gene could lead to uncontrolled cell growth. In order to determine the role of CDKN2A in the development of sporadic ovarian cancer, loss of heterozygosity at 9p21-22, homozygous del...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690621
更新日期:1999-08-01 00:00:00
abstract::A sedentary lifestyle, obesity, and a Westernized diet have been implicated in the aetiology of both colorectal cancer and non-insulin dependent diabetes mellitus, leading to the hypothesis that hyperinsulinaemia may promote colorectal cancer. We prospectively examined the association between colorectal cancer risk an...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1582
更新日期:2001-02-02 00:00:00
abstract:BACKGROUND:We aimed to assess the efficacy of second-line fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer (BTC) after failure of gemcitabine plus cisplatin (GEMCIS). METHODS:We retrospectively examined patients with histologically documented advanced BTC who received first-line GEMCI...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.446
更新日期:2017-02-28 00:00:00
abstract::To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/sj.bjc.6601985
更新日期:2004-08-02 00:00:00
abstract::Increasingly, treatment choices leading to the same survival outcome can be offered to cancer patients (e.g. mastectomy or conservative surgery in early breast cancer). Two approaches available for post-orchidectomy, stage I patients with non-seminomatous germ cell tumours of the testis (NSGCTT), particularly those at...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.570
更新日期:1996-11-01 00:00:00