Prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) in cytosols and pellet extracts derived from 892 breast cancer patients

To evaluate the clinical relevance of urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) measured by a recently developed enzyme-linked immunosorbent assay (ELISA), we analysed both components in samples derived from 892 patients with primary breast cancer (median follow-up 99 months). The assays were performed in cytosolic extracts as well as in corresponding detergent extracts of pellets obtained after ultracentrifugation, which was carried out when preparing the cytosolic fractions for routine steroid hormone receptor determination. Statistically significant correlations were found between the cytosolic levels and those determined in the pellet extracts (Spearman correlation coefficient rs = 0.60, P < 0.0001 for uPA and rs = 0.65, P < 0.0001 for PAI-1). Furthermore, strong correlations were found between the levels of both uPA (rs = 0.85, P < 0.0001) and PAI-1 (rs = 0.90, P < 0.0001) in the cytosols and their levels previously measured with ELISAs based on commercial reagents. In both Cox univariate and multivariate analysis, high cytosolic levels of uPA or PAI-1 were significantly associated with increased rates of relapse and death. The levels of uPA and PAI-1 in the pellet extracts also provided prognostic information, although to a lesser extent compared with the cytosolic extracts. The prediction of prognosis on the basis of uPA and PAI-1 assessed by an alternative ELISA once again emphasizes the established prognostic role and usefulness of these parameters in selection of breast cancer patients at high or low risk of recurrence. © 1999 Cancer Research Campaig

Microscopic Calculation of in-Medium Proton-Proton Cross Sections

We derive in-medium PROTON-PROTON cross sections in a microscopic model based upon the Bonn nucleon-nucleon potential and the Dirac-Brueckner approach for nuclear matter. We demonstrate the difference between proton-proton and neutron-proton cross sections and point out the need to distinguish carefully between the two cases. We also find substantial differences between our in-medium cross sections and phenomenological parametrizations that are commonly used in heavy-ion reactions.Comment: 9 pages of RevTex and 4 figures (postscript in separate uuencoded file), UI-NTH-930

Digital material laboratory: Wave propagation effects in open-cell aluminium foams

This paper is concerned with numerical wave propagation effects in highly porous media using digitized images of aluminum foam -- Starting point is a virtual material laboratory approach -- The Aluminum foam microstructure is imaged by 3D X-ray tomography -- Effective velocities for the fluid-saturated media are derived by dynamic wave propagation simulations -- We apply a displacement-stress rotated staggered fnite-difference grid technique to solve the elastodynamic wave equation -- The used setup is similar to laboratory ultrasound measurements and the computed results are in agreement with our experimental data -- Theoretical investigations allow to quantify the influence of the interaction of foam and fluid during wave propagation – Together with simulations using an artificial dense foam we are able to determine the tortuosity of aluminum foa

Local Causal States and Discrete Coherent Structures

Coherent structures form spontaneously in nonlinear spatiotemporal systems and are found at all spatial scales in natural phenomena from laboratory hydrodynamic flows and chemical reactions to ocean, atmosphere, and planetary climate dynamics. Phenomenologically, they appear as key components that organize the macroscopic behaviors in such systems. Despite a century of effort, they have eluded rigorous analysis and empirical prediction, with progress being made only recently. As a step in this, we present a formal theory of coherent structures in fully-discrete dynamical field theories. It builds on the notion of structure introduced by computational mechanics, generalizing it to a local spatiotemporal setting. The analysis' main tool employs the \localstates, which are used to uncover a system's hidden spatiotemporal symmetries and which identify coherent structures as spatially-localized deviations from those symmetries. The approach is behavior-driven in the sense that it does not rely on directly analyzing spatiotemporal equations of motion, rather it considers only the spatiotemporal fields a system generates. As such, it offers an unsupervised approach to discover and describe coherent structures. We illustrate the approach by analyzing coherent structures generated by elementary cellular automata, comparing the results with an earlier, dynamic-invariant-set approach that decomposes fields into domains, particles, and particle interactions.Comment: 27 pages, 10 figures; http://csc.ucdavis.edu/~cmg/compmech/pubs/dcs.ht

External quality assessment of trans-European multicentre antigen determinations (enzyme-linked immunosorbent assay) of urokinase-type plasminogen activator (uPA) and its type 1 inhibitor (PAI-1) in human breast cancer tissue extracts.

High levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in breast cancer tissue extracts have been associated with rapid disease progression. In these studies, different enzyme-linked immunosorbent assay (ELISA) kits have been applied for the quantification, and consequently the ranges of uPA and PAI-1 levels reported differ considerably. Therefore, the Receptor and Biomarker Study Group (RBSG) of the European Organization for Research and Treatment of Cancer (EORTC) and a consortium of the BIOMED-1 project 'Clinical Relevance of Proteases in Tumor Invasion and Metastasis' initiated three collaborative between-laboratory assessment trials aimed at controlling uPA and PAI-1 antigen analyses. For this purpose, two control preparations were produced from different sources: pooled human breast cancer specimens (QC-240893) and human breast cancer xenografts raised in nude mice (QC-101094). The lyophilized preparations were stable for prolonged times (at least 3 and 27 months respectively) at 4 degrees C. Furthermore, a good parallelism following dilution was found for uPA and PAI-1. The data from QC trial no. 1 clearly indicated that acceptable between-laboratory coefficients of variation (CVs) for uPA (<8.2%) and PAI-1 (<16.6%) in QC-240893 could be achieved when the same type of ELISA kit (American Diagnostica) was used. From the second trial, in which ten EORTC laboratories each received five identical lyophilized QC-101094 samples, it appeared that the within-laboratory variations for uPA and PAI-1 determinations obtained by 'experienced' laboratories were lower (<12.9%) than those from non-experienced laboratories (<36.4%). In a third QC trial, five BIOMED-1 laboratories, all of which employed ELISA procedures for uPA and PAI-1, participated in six subsequent quality assessment rounds receiving five samples of QC-101094. Although for each laboratory the within-run CVs for uPA as well as for PAI-1 were low (<7.8%), the between-run CVs were found to be considerably higher (up to 56.2% for uPA and to 27.6% for PAI-1). Consequently, because of the different ELISA formats used, the absolute analyte values measured in the different laboratories varied substantially. The use of 'common external standards' in the different ELISAs resulted in a significant reduction of the between-laboratory CVs from 61.3% to 15.7% (uPA) and from 42.1% to 19.1% (PAI-1). The present data demonstrate that in multicentre studies the same ELISA kit should be used, and that external quality assurance (QA) is mandatory. Furthermore, it appears from the present study that standardization of the protein assay as a tissular parameter is imperative

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

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Comparison of immunohistochemistry with immunoassay (ELISA) for the detection of components of the plasminogen activation system in human tumour tissue

Enzyme-linked immunosorbent assay (ELISA) methods and immunohistochemistry (IHC) are techniques that provide information on protein expression in tissue samples. Both methods have been used to investigate the impact of the plasminogen activation (PA) system in cancer. In the present paper we first compared the expression levels of uPA, tPA, PAI-1 and uPAR in a compound group consisting of 33 cancer lesions of various origin (breast, lung, colon, cervix and melanoma) as quantitated by ELISA and semi-quantitated by IHC. Secondly, the same kind of comparison was performed on a group of 23 melanoma lesions and a group of 28 breast carcinoma lesions. The two techniques were applied to adjacent parts of the same frozen tissue sample, enabling the comparison of results obtained on material of almost identical composition. Spearman correlation coefficients between IHC results and ELISA results for uPA, tPA, PAI-1 and uPAR varied between 0.41 and 0.78, and were higher for the compound group and the breast cancer group than for the melanoma group. Although a higher IHC score category was always associated with an increased median ELISA value, there was an overlap of ELISA values from different scoring classes. Hence, for the individual tumour cases the relation between ELISA and IHC is ambiguous. This indicates that the two techniques are not directly interchangeable and that their value for clinical purposes may be different. © 1999 Cancer Research Campaig