Tissue-type plasminogen activator in plasma from breast cancer patients determined by enzyme-linked immunosorbent assay

Abstract

Summary An enzyme-linked immunosorbent assay (ELISA) using monoclonal and polyclonal antibodies against t-PA was used to measure the concentration of tissue-type plasminogen activator (t-PA) in plasma from 34 healthy donors and 92 breast cancer patients with a varying extent of disease. The mean value of t-PA in plasma for the healthy donors was 2.4 ± 2.1 ng ml'-(s.d.). The mean value for the breast cancer patients was 5.3 ± 4.3 ng ml '. This increase was statistically significant at the 1% level. There was a positive correlation between the mean t-PA plasma concentration and the extent of disease in different groups of patients. Taking 5.0 ng ml-l as cut-off point, about 40% of the patients were positive, and 6% of the normal controls were false positive. Twenty-five per cent of the patients in complete remission, 28% of the patients with minimal tumour burden, 60% of the patients with moderate tumour burden, and 90% of the patients with massive tumour burden were positive. It is possible that the patients with an elevated plasma t-PA represent a group with a particularly bad prognosis.

Prognostic value of tissue-type plasminogen activator (tPA) and its complex with the type-1 inhibitor (PAI-1) in breast cancer

“…Both uPA and PAI-1 are established prognostic factors in several types of cancer, a high tissue level of both components generally being associated with tumour progression and with poor disease-free and/or overall survival (reviewed by Duffy, 1996;Schmitt et al, 1997). Furthermore, several investigators have reported on the potential diagnostic and prognostic relevance of tPA analysed either in plasma or in tumour tissues from patients, including those afflicted with breast or colon cancer (Layer et al, 1987;De Bruin et al, 1988;Duffy et al, 1988;Needham et al, 1988;Grøndahl-Hansen et al, 1990;Jänicke et al, 1990Jänicke et al, , 1991Rella, et al, 1993;Yamashita et al, 1993Yamashita et al, , 1995Duggan et al, 1997). In addition, some studies even have examined the presence of complexes between tPA and PAI-1 in plasma from healthy individuals and patients with various diseases (Niwano et al, 1992;Hansson et al, 1994;Maser et al, 1997).…”

Quality control for HPLC assay and surrogate end point biomarkers from the fenretinide (4-HPR) breast cancer prevention trial

“…Breast cancer patients with tumors with a high t-PA content had a better prognosis than those with low t-PA [Duffy et al, 1988]. In any case, the mean plasma levels of t-PA have been found to be higher in breast cancer patients than in healthy donors [Grondahl-Hansen et al, 1990;Mannucci et al, 1990], with a positive correlation between the mean t-PA plasma concentration and extent of the disease. In a subset of patients participating in the trial, we investigated the effects of 4-HPR on circulating PA levels.…”

Urokinase receptors on human monocytes in angina pectoris

“…Neuroimmunomodulatory function of sero= tonin (5-HT) has been demonstrated [3,4]. It was shown that activation of serotoninergic mechanisms in the central nervous system is accompanied by suppression of the immune system mediated through pituitary-adrenal regulatory mechanisms.…”

“…These cells also possess urokinase receptors (URR). Urokinase is primarily associated with cells, and only low UR concentration is present in the plasma [4]. Expression of URR dramatically increases in arterial lesions, atheromas, and atherosclerotie plaques [8,10].…”