Abstract:
:The prognostic value of tissue-type plasminogen activator (tPA) measured in samples derived from 865 patients with primary breast cancer using a recently developed enzyme-linked immunosorbent assay (ELISA) was evaluated. Since the assay could easily be adapted to the assessment of the complex of tPA with its type-1 inhibitor (PAI-1), it was investigated whether the tPA:PAI-1 complex also provides prognostic information. To this end, cytosolic extracts and corresponding detergent extracts of 100,000 g pellets obtained after ultracentrifugation when preparing the cytosolic fractions for routine steroid hormone receptor determination were assayed. Statistically significant correlations were found between the cytosolic levels and those determined in the pellet extracts (Spearman correlation coefficient r(s) = 0.75, P < 0.001 for tPA and r = 0.50, P < 0.001 for tPA:PAI-1 complex). In both Cox univariate and multivariate analysis elevated levels of (total) tPA determined in the pellet extracts, but not in cytosols, were associated with prolonged relapse-free (RFS) and overall survival (OS). In contrast, high levels of the tPA:PAI-1 complex measured in cytosols, but not in the pellet extracts, were associated with a poor RFS and OS. The prognostic information provided by the cytosolic tPA:PAI-1 complex was comparable to that provided by cytosolic (total) PAI-1. Furthermore, the estimated levels of free, uncomplexed tPA and PAI-1, in cytosols and in pellet extracts, were related to patient prognosis in a similar way as the (total) levels of tPA and PAI-1 respectively. Determination of specific forms of components of the plasminogen activation system, i.e. tPA:PAI-1 complex and free, uncomplexed tPA and/or PAI-1, may be considered a useful adjunct to the analyses of the separate components (tPA and/or PAI-1) and provide valuable additional prognostic information with respect to survival of breast cancer patients.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
de Witte JH,Sweep CG,Klijn JG,Grebenschikov N,Peters HA,Look MP,van Tienoven TH,Heuvel JJ,Bolt-De Vries J,Benraad TJ,Foekens JAdoi
10.1038/sj.bjc.6690353subject
Has Abstractpub_date
1999-04-01 00:00:00pages
286-94issue
1-2eissn
0007-0920issn
1532-1827journal_volume
80pub_type
杂志文章abstract::Prostate-specific antigen (PSA) is a serine protease secreted at low levels by normal luminal epithelial cells of the prostate and in significantly higher levels by prostate cancer cells. Therefore, PSA is a potential target for various immunotherapeutical approaches against prostate cancer. DNA vaccination has been i...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
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更新日期:2004-08-16 00:00:00
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abstract::Caffeine has for many years been known to be involved in the sensitization of DNA to damage. One potential mechanism recently put forward is an override of the G2/M block induced by irradiation, which would leave the cells less time for DNA repair prior to mitosis. However, different cell types display a variety of re...
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journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
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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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journal_title:British journal of cancer
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.60
更新日期:1994-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjc.6603870
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pub_type: 杂志文章
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journal_title:British journal of cancer
pub_type: 杂志文章
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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:2005-08-01 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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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.177
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journal_title:British journal of cancer
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doi:10.1038/bjc.1976.63
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