Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is no information available on the relation between response to chemotherapy and the high-risk phenotype assessed by uPA and/or PAI-1. The clinical situation of neoadjuvant chemotherapy provides a means of rapidly assessing the sensitivity of the primary tumour to cytotoxic drug regimens. The goal of the study was to assess prospectively the predictive value of PAI-1 for response to first-line chemotherapy. PAI-1 concentration was measured on hypertonic cytosolic extracts (0.4 M potassium chloride) by ELISA before chemotherapy on a drill biopsy sample of the tumour in 69 T2 and T3 breast cancer patients (median age 46 years). Oestrogen receptor (ER) (51% ER+), progesterone receptor (PR) (58% PR+), S-phase (median 4.0%) and ploidy were also assessed in the majority of cases. The clinical response to treatment was evaluated after four cycles of FAC or FEC regimen (5-fluorouracil, epidoxorubicin or doxorubicin and cyclophosphamide) (one cycle every 4th week). PAI-1 could be assayed in 29 post-chemotherapy surgical samples. The objective response rate (complete response plus partial response) was 59% (41 out of 69). PAI-1 expressed as gram of tissue (range 19-2370 ng g(-1) tissue) was highly correlated (r = 0.98) to PAI-1 expressed as mg protein (range 0.5-68 ng mg(-1) protein). No correlation between PAI-1 level and response could be observed, with any cut-off. The post- and pre-chemotherapy PAI-1 levels were correlated (r = 0.66). Of all biological parameters, only high S-phase (cut-off 5%) was slightly correlated (chi2 = 3.91, P = 0.05) to response. These data suggest that PAI-1 is not a predictive marker of response to chemotherapy in breast cancer and that its level is not altered by neoadjuvant chemotherapy.
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PMID:Plasminogen activator inhibitor-1 (PAI-1) is not related to response to neoadjuvant chemotherapy in breast cancer. 927 33

Proteases are involved in the invasion and metastasis of tumours by destruction of the basal membrane and connective tissue. As levels in malignant tissue have both prognostic and therapeutic implications, we examined 318 frozen samples from malignant tumours and comparable non-malignant tissue looking for urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels with ELISA, as well as cathepsin D with RIA. Oestrogen receptor (ER) levels, progesterone receptor (PrgR) levels and epidermal growth factor receptors (EGFR) were measured by biochemical methods at the same time. Significantly raised levels of uPA, PAI-1 and cathepsin D were found in malignant tissue, with PAI-1 particularly high in carcinoma of the cervix. Significantly raised tPA levels were found in breast cancer tissue with a more favourable clinical prognosis, with a positive correlation between tPA and ER. No correlation could be shown between uPA, PAI-1 and cathepsin D with other prognostic factors for breast cancer. It could be that routine, uncomplicated estimation of tumour-associated proteases such as uPA, tPA, PAI-1 and cathepsin D will provide an independent prognostic marker for therapeutic decisions with regard to gynaecological tumours and breast cancer.
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PMID:Proteases associated with gynecological tumors. 2156 82