Tranexamic acid is an active site inhibitor of urokinase plasminogen activator.
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ABSTRACT:
SUBMITTER: Wu G
PROVIDER: S-EPMC6418500 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Tranexamic acid is an active site inhibitor of urokinase plasminogen activator.
Wu Guojie G Mazzitelli Blake A BA Quek Adam J AJ Veldman Matthew J MJ Conroy Paul J PJ Caradoc-Davies Tom T TT Ooms Lisa M LM Tuck Kellie L KL Schoenecker Jonathan G JG Whisstock James C JC Law Ruby H P RHP
Blood advances 20190301 5
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2011-05-03 | GSE29028 | GEO
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Project description:BackgroundProtein levels of urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) determined by enzyme-linked immunosorbent assay from fresh-frozen tumor tissue have been evaluated as prognostic factors in prospectively randomized trials in breast cancer. However, the role of uPA and PAI-1 in the context of breast cancer subtypes and for mRNA expression of these factors is less clear.MethodsWe evaluated uPA and PAI-1 mRNA expression using the Affymetrix HG-U 133A array within molecular subgroups of breast cancer in cohorts of patients with systemic treatment (cohort A, n=362) and without systemic treatment (cohort B, n=200). We validated mRNA expression in a cohort of HER2-positive breast cancer patients (cohort C, n=290). Luminal, triple-negative, and HER2-positive subcohorts were defined by ESR1 and ERBB2 mRNA expression using predefined cutoffs.ResultsIn the entire cohort A, elevated PAI-1 but not uPA mRNA expression was associated with shorter disease-free survival (P=0.007 for PAI and 0.069 for uPA). Regarding different molecular subgroups, 67% (n=244) of tumors were luminal, 14% (n=49) were HER2-positive, and 19% (n=69) were triple-negative. Elevated PAI-1 mRNA expression was associated with shorter disease-free survival only in the HER2-positive subgroup (P=0.031). The same disease-free survival results were found for uPA in HER2-positive patients (P=0.011). In contrast, no association between either marker and survival was observed in the luminal or triple-negative subgroups. In the HER2-positive validation cohort C, elevated uPA and PAI-1 mRNA expression also showed strong associations with shorter disease-free survival (P=0.014 for PAI-1, P<0.001 for uPA).ConclusionIn this study, the prognostic impact of uPA and PAI-1 expression was mainly observed in patients with HER2-positive tumors.
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2011-05-03 | E-GEOD-29028 | biostudies-arrayexpress
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Project description:BackgroundOne of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer.MethodsThe study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR.ResultsuPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value.ConclusionThese findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer patients.
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