Abstract:
:Resistance to cytotoxics precludes the successful treatment of many solid tumours. Inhibition of DNA synthesis in normal tissues with antimetabolites such as hydroxyurea (HU) may be a useful means of improving the selective uptake of toxic thymidine analogues by the relatively resistant tumour cells. HU also inhibits DNA repair by the critical depletion of intracellular deoxyribonucleotides. Twenty-five patients with various malignancies received 5-iodo-2-deoxyuridine (IUdR) 100 mg m-2 as a 20 min i.v. infusion and the uptake of IUdR was determined 1 h later immunocytochemically. Of these patients, 14 received IUdR 23 h from the start of a continuous i.v. infusion of HU (36 g over 36 h). Uptake of IUdR was equally suppressed in bone marrow and tumour aspirates, 0.1% (+/- 0.2%) of marrow precursor cells and 0.5% (+/- 0.4%) of tumour cells respectively, in patients who received HU compared to the uptake of IUdR in 11 patients who were not given HU 6.8% (+/- 1.1%) and 12.2% (+/- 1.8%) respectively. Mean HU plasma concentrations at the time of IUdR administration was 1.7 +/- 0.2 mM. The growth fraction of tumour cells (using Ki67 labelling) was not changed after treatment with HU. It is concluded that (1) since DNA synthesis is effectively inhibited by HU in tumour cells, differential uptake of radiolabelled IUdR by those cells will not be feasible using the current schedule of HU administration, (2) HU may be used as an inhibitor of DNA repair in vivo since the degree of inhibition correlates with that required to inhibit repair experimentally and that (3) Ki67 labelling index is not useful in studying cell kinetics in patients treated with HU.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Philip PA,Kaklamanis L,Carmichael J,Tonkin K,Morrison H,Gatter K,Harris ALdoi
10.1038/bjc.1993.120subject
Has Abstractpub_date
1993-04-01 00:00:00pages
644-9issue
4eissn
0007-0920issn
1532-1827journal_volume
67pub_type
杂志文章abstract:BACKGROUND:Bladder cancer (BC) predominantly affects the elderly and is often the cause of death among patients with muscle-invasive disease. Clinicians lack quantitative estimates of competing mortality risks when considering treatments for BC. Our aim was to determine the bladder cancer-specific mortality (CSM) rate ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.106
更新日期:2013-04-16 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::Pulmonary metastasectomy is widely and increasingly practiced in the belief that this intervention can cure patients with colorectal cancer, and that without it few survive 5 years. No good evidence exists supporting such convictions, indeed recent trial results challenge them. What evidence underpins this acceptance ...
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更新日期:2020-08-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.196
更新日期:1994-06-01 00:00:00
abstract::The humanised form of an antagonistic anti-IGF-1R mAb (AVE1642) selectively inhibits the growth of CD45(neg) myeloma cells. AVE1642 strongly increased bortezomib-induced apoptosis, correlated with an increase of Noxa expression. These results support the therapeutic use of anti-IGF-1R/bortezomib in CD45(neg) Myeloma p...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604839
更新日期:2009-01-27 00:00:00
abstract::We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). We also examined the relation between DNA ploidy pattern and the response to chemotherapy. A total of 267 patients with NSCLC (pathologically documented stage I, II, or IIIA) underw...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/sj.bjc.6603336
更新日期:2006-10-09 00:00:00
abstract::Oral capecitabine is a highly active, well-tolerated and convenient treatment for breast and colorectal cancer. This trial assessed the efficacy and safety of single-agent capecitabine in patients with previously treated ovarian cancer. A total of 29 patients with platinum-pretreated relapsed ovarian cancer were enrol...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6601381
更新日期:2003-11-17 00:00:00
abstract::Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) have been increasingly recognized to play an important role in the pathobiology of pancreatic malignancy. We have investigated the effects of FGF-1 and FGF-2 on the behaviour and adhesion properties of human pancreatic adenocarcinoma cell ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.1813
更新日期:2001-06-15 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1979.250
更新日期:1979-11-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.353
更新日期:1994-10-01 00:00:00
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journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
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更新日期:2004-10-18 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.406
更新日期:1991-11-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/s41416-019-0474-x
更新日期:2019-06-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.258
更新日期:1998-05-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.1994.105
更新日期:1994-03-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.222
更新日期:1983-10-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.bjc.6605319
更新日期:2009-10-20 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjc.6692231
更新日期:1999-12-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1988-08-01 00:00:00
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journal_title:British journal of cancer
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:2014-09-23 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章,评审
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更新日期:1998-06-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:2013-06-11 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1973-09-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:2000-12-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1986-06-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1993-04-01 00:00:00
abstract::Killing of autologous melanoma (auto-Me) was obtained with pooled allostimulated peripheral blood lymphocytes (PBL) in 34/42 cases and found not to be due to a cross-reactivity between melanoma and allogeneic normal antigens. To see whether generation of tumour cytotoxic PBL by allostimulation was due to release of IL...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1985.151
更新日期:1985-07-01 00:00:00
abstract::Differences were seen in the ability of 2 strains of C. parvum to augment cytotoxicity attributable to NK cells towards a rat lymphoma. Furthermore, 2 batches of the same strain of C. parvum prepared by different methods also differed in their ability to augment cytotoxicity. Other factors influencing cytotoxicity wer...
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pub_type: 杂志文章
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更新日期:1980-07-01 00:00:00