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  • 1
    Electronic Resource
    Electronic Resource
    Estrogen receptor alpha ( ESR1 ) gene amplification is frequent in breast cancer (2007)
    [s.l.] : Nature Publishing Group
    Nature genetics 39 (2007), S. 655-660 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha, at 6q25. A subsequent tissue microarray analysis of more than 2,000 clinical breast cancer samples showed ESR1 ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/ng2006
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  • 2
    Electronic Resource
    Electronic Resource
    Urokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer (1993)
    Springer
    Breast cancer research and treatment 24 (1993), S. 195-208 
    Details
    ISSN: 1573-7217
    Keywords: protease ; inhibitor ; urokinase ; uPA ; PAI-1 ; cathepsin D ; prognosis ; breast cancer ; axillary node-negative patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor-associated proteases, which promote the dissolution of the surrounding tumor matrix and the basement membranes. The serine protease urokinase-type plasminogen activator (uPA), which is elevated in solid tumors, appears to play a key role in these processes. We used enzyme-linked immunoassays (ELISA) to test for uPA antigen and its inhibitor PAI-1 in tumor tissue extracts of 247 breast cancer patients who were enrolled in a prospective study. The relation of these data to known prognostic factors and to other variables such as DNA analysis and cathepsin D was studied. Disease-free and overall survival were analyzed according to Cox's proportional hazard model. The major new finding is that breast cancer patients with either high uPA (〉2.97 ng/mg protein) or high content of the uPA inhibitor PAI-1 (〉2.18 ng/mg protein) in their primary tumors have an increased risk of relapse and death. Multivariate analyses revealed uPA to be an independent and strong prognostic factor. The impact of uPA is as high as that of the lymph node status. In node-negative patients the impact of uPA is closely followed by that of PAI-1. Since uPA and PAI-1 are independent prognostic factors, the node-negative patients could be subdivided further by combining these two variables. In this refined analysis, patients whose primary tumors have lower levels of both antigens evidently have a very low risk of relapse (93% disease-free survival at three years) in contrast to patients with high uPA and high PAI-1 (55% disease-free survival at three years). The combination of uPA and PAI-1 in our group of patients with axillary node-negative breast cancer allows us to identify the 45 percent of patients having an increased risk of relapse. Consequently, more than half of the patients had less than a 10% probability of relapse and thus would possibly be candidates for being spared the necessity of adjuvant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01833260
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    The urokinase plasminogen activator system as a target for prognostic studies in breast cancer (1998)
    Springer
    Breast cancer research and treatment 52 (1998), S. 99-111 
    Details
    ISSN: 1573-7217
    Keywords: prognostic factor trials ; statistical methods ; urokinase plasminogen activator system ; PAI-1 ; PAI-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The identification of patients at high risk of relapse is currently one of the most important issues in breast cancer research. However, the selection of high-risk patients continues to be difficult due to the unpredictable course of this disease. Axillary lymph node status is currently recognized as the best clinical discriminant between good and poor prognosis, yet almost 30% of node- negative patients and 65% of node-positive patients will experience a relapse. Additional prognostic markers are therefore urgently needed. Since metastatic disease is the main cause of cancer patient morbidity and mortality, the measurement of molecules functionally involved in the regulation of tumor invasion and metastasis is attractive as a means to predict prognosis. Cancer invasion is a complex process in which degradation of the extracellular matrix plays a crucial role. This degradation is accomplished by the concerted action of several proteolytic enzyme systems, including generation of plasmin by the urokinase pathway of plasminogen activation, matrix metallo-proteases, and other extracellular proteases. Increased expression and secretion of urokinase plasminogen activator (uPA) strongly correlates with the malignant phenotype of many types of cells, and the central role of uPA in tumor invasion is now well established. This review will focus on the prognostic impact of components of the urokinase plasminogen activation system in breast cancer with emphasize on methodological issues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006115218786
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  • 4
    Electronic Resource
    Electronic Resource
    Invasion marker PAI‐1 remains a strong prognostic factor after long‐term follow‐up both for primary breast cancer and following first relapse (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 147-157 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cathepsin D ; PAI‐1 ; prognosis ; S‐phase fraction ; uPA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 1991, our group was the first to report the prognostic strength of plasminogen activator inhibitor type 1 (PAI‐1) in primary breast cancer. The prognostic impact of invasion markers PAI‐1 and urokinase‐type plasminogen activator (uPA) on disease‐free survival (DFS) and overall survival (OS) in breast cancer has since been independently confirmed. We now report on the prognostic impact of PAI‐1 and uPA after long‐term median follow‐up of 77 months for our cohort (n=316). Levels of uPA, PAI‐1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. S‐phase fraction (SPF) was measured flowcytometrically in paraffin sections. Using log‐rank statistics, optimized cutoffs were found for PAI‐1 (14 ng/mg), uPA (3 ng/mg), cathepsin D (41 pmol/mg), and SPF (6%). In all patients, various factors (PAI‐1, uPA, nodal status, SPF, cathepsin D, grading, tumor size, hormone receptor status) showed significant univariate impact on DFS. In Cox analysis, only nodal status (p 〈 0.001, RR: 3.1) and PAI‐1 (p 〈 0.001, RR: 2.7) remained significant. In node‐negative patients (n = 147), PAI‐1, uPA, and SPF had significant univariate impact on DFS, whereas in Cox analysis, only PAI‐1 was significant. PAI‐1 was also significant for DFS within subgroups defined by established factors. In CART analysis, uPA enhanced the prognostic value of PAI‐1 and nodal status for determination of a very‐low‐risk subgroup. For OS, only lymph node status and PAI‐1 were significant in multivariate analysis. PAI‐1 levels in the primary tumor were also a significant prognostic marker for survival after first relapse in both univariate and multivariate analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006118828278
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    Paper (German National Licenses)
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