Abstract:
:5-fluorouracil (5FU) is activated intracellularly to cytotoxic 5-fluoronucleotides (FNuct). These were detected non-invasively in rats bearing the Walker carcinosarcoma by 19F-magnetic resonance spectroscopy (MRS) following an i.v. bolus dose of 5FU (50 mg kg-1). Pre-treatment of the rats (3 to 24 h earlier) by methotrexate (MTX) (20 or 50 mg kg-1) did not affect the rate of 5FU disappearance but did significantly increase the rate of FNuct formation (P less than 0.002) and the final amount formed (P less than 0.02) as assessed by MRS in vivo. MTX (20 mg kg-1) caused substantially the same effects on FNuct formation (P less than 0.002 for rate and P less than 0.05 for the amount) when 5FU was administered i.p. although higher doses of 5FU (120 mg kg-1) were necessary to observe the 19F-signals. Quantitative analysis by MRS in vitro of extracts from the freeze-clamped tumours treated by 5FU i.v. confirmed that MTX pre-treatment increased FNuct formation 3-fold (P less than 0.05). Hplc quantitative analysis demonstrated that 50% of the FNuct was the cytotoxic nucleotide FUTP which was also increased 3-fold in MTX treated animals (P less than 0.05). Since the Walker tumour is probably sensitive to 5FU action via FUTP incorporation into RNA, these results suggested that drug regimes in which MTX preceded 5FU (MTX-5FU schedule) would be more cytotoxic that 5FU alone. At an MTX dose of 20 mg kg-1 24 h prior to 5FU there was significant inhibition of growth (P less than 0.05) compared to no treatment, MTX alone or the reverse schedule of 5FU-MTX. These results suggest MRS may be of clinical value in optimising chemotherapy using schedules where MTX precedes 5FU.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
McSheehy PM,Prior MJ,Griffiths JRdoi
10.1038/bjc.1992.75subject
Has Abstractpub_date
1992-03-01 00:00:00pages
369-75issue
3eissn
0007-0920issn
1532-1827journal_volume
65pub_type
杂志文章abstract::Vascular endothelial growth factor (VEGF) is recognized to play a predominant role in breast cancer prognosis. The action of VEGF is mediated by two high-affinity receptors with ligand-stimulated tyrosine kinase activity: VEGFR-1/flt-1 and VEGFR-2/flk-1, which are expressed mainly in vascular endothelial cells. To the...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6692206
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journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
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journal_title:British journal of cancer
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更新日期:1987-09-01 00:00:00
abstract::Insoluble conanavalin A and wheat germ agglutinin (WGA) were found to bind to carbohydrates on radio-labelled carcinoembryonic antigen (CEA). Binding by WGA was inhibited both by N-acetyl D-glucosamine and fragments of antibody to CEA, but was increased by intact antibody to CEA. This suggests that WGA binds to expose...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.63
更新日期:1975-03-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1985.151
更新日期:1985-07-01 00:00:00
abstract:BACKGROUND:MYCN amplification with subsequent MYCN protein overexpression is a powerful indicator of poor prognosis of neuroblastoma patients. Little is known regarding the prognostic significance of the homologous MYC protein expression in neuroblastoma. METHODS:Immunostaining for MYCN and MYC protein was performed o...
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604508
更新日期:2008-08-19 00:00:00
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更新日期:2015-04-28 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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更新日期:2004-03-08 00:00:00
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pub_type: 杂志文章
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更新日期:1977-06-01 00:00:00
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更新日期:1980-12-01 00:00:00
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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
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更新日期:1997-01-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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