المؤلفون: Buhl, I.K., Gerster, S., Delorenzi, M., Jensen, T., Jensen, P.B., Bosman, F., Tejpar, S., Roth, A., Brunner, N., Hansen, A., Knudsen, S.

المصدر: PloS one, vol. 11, no. 5, pp. e0155123

مصطلحات موضوعية: Camptothecin/analogs & derivatives, Camptothecin/pharmacology, Camptothecin/therapeutic use, Cell Line, Tumor, Chemotherapy, Adjuvant, Clinical Trials as Topic, Cohort Studies, Colonic Neoplasms/drug therapy, Colonic Neoplasms/genetics, Disease-Free Survival, Drug Evaluation, Preclinical, Fluorouracil/pharmacology, Fluorouracil/therapeutic use, Gene Expression Profiling, Gene Expression Regulation, Neoplastic/drug effects, Humans, Prognosis

الوصف: This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. To test if an irinotecan signature and a SN-38 signature could identify patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer patients enrolled in the PETACC-3 prospective randomized clinical trial. A 5-FU profile developed similarly was assessed by comparing the PETACC-3 cohort with a cohort of 359 stage II colon cancer patients who underwent surgery but received no adjuvant therapy. There was no statistically significant association between the irinotecan or SN-38 profiles and benefit from irinotecan. The 5-FU sensitivity profile showed a statistically significant association with relapse free survival (RFS) (hazard ratio (HR) = 0.54 (0.41-0.71), p<1e-05) and overall survival (HR = 0.47 (0.34-0.63), p<1e-06) in the PETACC-3 subpopulation. The effect of the 5-FU profile remained significant in a multivariable Cox Proportional Hazards model, adjusting for several relevant clinicopathological parameters. No statistically significant effect of the 5-FU profile was observed in the untreated cohort of 359 patients (relapse free survival, p = 0.671). The irinotecan predictor had no predictive value. The 5-FU predictor was prognostic in stage III patients in PETACC-3 but not in stage II patients with no adjuvant therapy. This suggests a potential predictive ability of the 5-FU sensitivity profile to identify colon cancer patients who may benefit from 5-FU, however, any biomarker predicting benefit for adjuvant 5-FU must be rigorously evaluated in independent cohorts. Given differences between the two study cohorts, the present results should be further validated.

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/27171152; info:eu-repo/semantics/altIdentifier/eissn/1932-6203; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_E521F016CAEB1; https://serval.unil.ch/notice/serval:BIB_E521F016CAEBTest; urn:issn:1932-6203; https://serval.unil.ch/resource/serval:BIB_E521F016CAEB.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_E521F016CAEB1Test

الإتاحة: https://doi.org/10.1371/journal.pone.0155123Test
https://serval.unil.ch/notice/serval:BIB_E521F016CAEBTest
https://serval.unil.ch/resource/serval:BIB_E521F016CAEB.P001/REF.pdfTest
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_E521F016CAEB1Test

المؤلفون: Wurtz, S Ö, Lutken Henriksen, K, Lykkesfeldt, A, Celis, J, Brunner, N Å

المصدر: Ugeskrift for Laeger. 169(36):2999

المؤلفون: Brunner, N Å

المصدر: Ugeskrift for Laeger. 161(11):1577

المؤلفون: Look, M.P. (Maxime), Kueng, W., Klijn, J.G.M. (Jan), Broet, P., Eppenberger, U., Putten, W.L.J. (Wim) van, Ferno, M., Christensen, I.J., Lisboa, B.W., Thomssen, C. (Christoph), Kates, R. (Ronald), Magdelenat, H., Martin, P.M., Beex, L.V. (Louk), Windbichler, G., Janicke, F., Spyratos, F., Peyrat , J.P., Ricolleau, G., Cufer, T., Brunner, N., Meijer van Gelder, M.E. (Marion), Bendahl, P.O., Ulm, K., Schmitt, M. (Manfred), Sweep, C.G., Fiets, W.E., Duggan, C., Blankenstein, M.A. (Marinus), Borstnar, S., Daxenbichler, G., Eppenberger-Castori, S. (Serenella), Foekens, J.A. (John), O'Higgins, N., Duffy, M.J. (Michael), Daver, A., Manders, P. (Peggy), Romain, S., Quillien, V., Harbeck, N. (Nadia)

المصدر: National Cancer Institute. Journal (Print)

مصطلحات موضوعية: Adult, Aged, Biological Markers, Breast Neoplasms/*metabolism/*mortality/pathology, Female, Humans, Middle aged, Plasminogen Activator Inhibitor 1/*metabolism, Prognosis, Proportional Hazards Models, Research Support, Non-U.S. Gov't, Survival Analysis, Urinary Plasminogen Activator/*metabolism

الوصف: BACKGROUND: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAI-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). METHODS: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. RESULTS: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph node-negative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). CONCLUSIONS: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized ...

وصف الملف: application/pdf

العلاقة: http://repub.eur.nl/pub/9823Test; urn:hdl:1765/9823

الإتاحة: http://repub.eur.nl/pub/9823Test

المؤلفون: Foekens, J.A. (John), Henzen-Logmans, S.C. (Sonja), Klijn, J.G.M. (Jan), Putten, W.L.J. (Wim) van, Peters, H.A. (Harry), Look, M.P. (Maxime), Portengen, H. (Henk), Schmitt, M. (Manfred), Kramer, M.D., Brunner, N., Janicke, F., Meijer van Gelder, M.E. (Marion)

المصدر: Cancer Research

مصطلحات موضوعية: Adult, Aged, Breast Neoplasms/*enzymology/mortality, Disease-Free Survival, Female, Humans, Middle aged, Multivariate Analysis, Plasminogen Activator Inhibitor 1/analysis, Plasminogen Activator Inhibitor 2/analysis, Prognosis, Receptors, Cell Surface/analysis, Research Support, Non-U.S. Gov't, Urinary Plasminogen Activator/*metabolism

الوصف: The antigen levels of components of the urokinase-type plasminogen activator (uPA) system of plasminogen activation are correlated with prognosis in several types of cancers, including breast cancer. In the present study involving 2780 patients with primary invasive breast cancer, we have evaluated the prognostic importance of the four major components of the uPA system [uPA, the receptor uPAR (CD87), and the inhibitors PAI-1 and PAI-2]. The antigen levels were determined by ELISA in cytosols prepared from primary breast tumors. The levels of the four factors significantly correlated with each other; the Spearman rank correlation coefficients (r(s)) ranged from 0.32 (between PAI-2 and PAI-1 or uPAR) to 0.59 (between uPA and PAI-1). The median duration of follow-up of patients still alive was 88 months. In the multivariate analyses for relapse-free survival (RFS) and overall survival (OS), we defined a basic model including age, menopausal status, tumor size and grade, lymph node status, adjuvant therapy, and steroid hormone receptor status. uPA, uPAR, PAI-1, and PAI-2 were considered as categorical variables, each with two cut points that were established by isotonic regression analysis. Compared with tumors with low levels, those with intermediate and high levels showed a relative hazard rate (RHR) and 95% confidence interval (95% CI) of 1.22 (1.02-1.45) and 1.69 (1.39-2.05) for uPA, and 1.32 (1.14-1.54) and 2.17 (1.74-2.70) for PAI-1, respectively, in multivariate analysis for RFS in all patients. Compared with tumors with high PAI-2 levels, those with intermediate and low levels showed a poor RFS with a RHR (95% CI) of 1.30 (1.14-1.48) and 1.76 (1.38-2.24), respectively. Similar results were obtained in the multivariate analysis for OS in all patients. Furthermore, uPA and PAI-1 were independent predictive factors of a poor RFS and OS in node-negative and node-positive patients. PAI-2 also added to the multivariate models for RFS in node-negative and node-positive patients, and in the analysis for OS in ...

وصف الملف: application/pdf

العلاقة: http://repub.eur.nl/pub/9256Test; urn:hdl:1765/9256

الإتاحة: http://repub.eur.nl/pub/9256Test

المؤلفون: Riisbro, R, Christensen, IJ, Nielsen, HJ, Brunner, N, Nilbert, A, Fernebro, Eva

المصدر: International Journal of Biological Markers. 20(2):93-102

مصطلحات موضوعية: rectal cancer, soluble urokinase plasminogen receptor, suPAR, prognosis, Medicin och hälsovetenskap, Klinisk medicin, Cancer och onkologi, Medical and Health Sciences, Clinical Medicine, Cancer and Oncology

الوصف: Background and aims: Since approximately 30% of patients with Dukes' stage B colorectal cancer will experience disease recurrence within five years of primary treatment, current staging of patients with early colorectal cancer apparently fails to adequately predict patient outcome. It has previously been shown that the preoperative plasma concentration of soluble urokinase plasminogen activator receptor (suPAR) is associated with the survival of patients with early colorectal cancer. In this study we sought to confirm the independent prognostic value of suPAR in rectal cancer. Methods: suPAR was retrospectively determined by two different versions of a suPAR ELISA in preoperatively collected plasma samples from a Swedish (n=354) and a Danish (n=255) cohort of rectal cancer patients. Results: In both cohorts the suPAR concentration was significantly higher in Dukes' stage D patients than in Dukes' stage A-C patients (p < 0.0001). Among Dukes' stage A-C patients, no differences in median suPAR values were seen. In univariate analysis, continuous suPAR was found to be associated with survival (p < 0.0001 in both cohorts). Of particular interest was that similar results were obtained for Dukes' stage A and B patients when analyzed separately. In multivariate analysis, continuous suPAR was found in both cohorts to be independent of Dukes' stage. Conclusions: This study confirms that the preoperative concentration of plasma suPAR contains independent prognostic information on patients with rectal cancer. This result was independent of the two different versions of an in-house suPAR ELISA used to perform the analyses. The next step. in the evaluation of suPAR as a prognostic parameter in rectal cancer will be to launch an appropriately dimensioned prospective study where the benefit of applying preoperative plasma suPAR measurement to clinical decision-making regarding adjuvant therapy is assessed.

الوصول الحر: https://lup.lub.lu.se/record/233476Test

المؤلفون: Holten-Andersen, M, Christensen, IJ, Nilbert, Mef, Bendahl, Pär-Ola, Nielsen, HJ, Brunner, N, Fernebro, E

المصدر: European Journal of Cancer. 40(1):64-72

مصطلحات موضوعية: plasma, rectum, adenocarcinoma, TIMP-1, prognosis, Medicin och hälsovetenskap, Klinisk medicin, Cancer och onkologi, Medical and Health Sciences, Clinical Medicine, Cancer and Oncology

الوصف: The level of the tissue inhibitor of metalloproteinases 1 (TIMP-1) has previously been demonstrated to predict the survival of early stage colorectal cancer patients. The present study was undertaken to further validate plasma TIMP-1 as a prognostic marker in rectal cancer. Preoperative plasma from 352 rectal cancer patients were analysed using an immunoassay for TIMP-1. The TIMP-1 immunoassay demonstrated robustness and good reproducibility with low interassay coefficients of variation (CV). The rectal cancer patients had a mean plasma TIMP-1 level of 184 mug/l (standard deviation (SD): 70 mug/l). There were no significant differences in TIMP-1 levels between patients with Dukes' stage A, B or C disease, whereas Dukes' stage D patients had significantly increased TIMP-1 levels (P < 0.000 1); however, high levels of TIMP-1 were not restricted to those with advanced disease. Univariate analysis demonstrated an increasing risk of mortality with increasing TIMP-1 levels Hazard Ratio (HR)=2.9; 95% Confidence Interval (CI): 1.7-5.0; P<0.0001). Including additional covariates, multivariate analysis identified plasma T1MP-1 as an independent prognostic marker (HR=2.2; 95% CI: 1.2-4.1 (P 0.01). This study showed a highly significant and independent association between preoperative plasma TIMP-I levels and survival in rectal cancer patients, thus confirming our previous findings. Furthermore, the TIMP-1 immunoassay proved to be stable and reproducible in this confirmatory study. © 2003 Elsevier Ltd. All rights reserved.

الوصول الحر: https://lup.lub.lu.se/record/288400Test
http://dx.doi.org/10.1016/j.ejca.2003.09.019Test

المؤلفون: Look, M, van Putten, W, Duffy, M, Harbeck, N, Christensen, IJ, Thomssen, C, Kates, R, Spyratos, F, Fernö, Mårten, Eppenberger-Castori, S, Sweep, CGJF, Ulm, K, Peyrat, JP, Martin, PM, Magdelenat, H, Brunner, N, Duggan, C, Lisboa, BW, Bendah, PO, Quillien, V, Daver, A, Ricolleau, G, Meijer-Van Gelder, M, Manders, P, Fiets, WE, Blankenstein, M, Broet, P, Romain, S, Daxenbichler, G, Windbichler, G, Cufer, T, Borstnar, S, Kueng, W, Beex, L, Klijn, J, O'Higgins, N, Eppenberger, U, Janicke, F, Schmitt, M, Foekens, J

المصدر: Thrombosis and Haemostasis. 90(3):538-548

مصطلحات موضوعية: breast cancer, PAI-I, pooled-analysis, uPA, prognosis, Medicin och hälsovetenskap, Klinisk medicin, Kardiologi, Medical and Health Sciences, Clinical Medicine, Cardiac and Cardiovascular Systems

الوصف: In this report we present an extension of the pooled analysis of the prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I in breast cancer patients. We analyzed a different endpoint, metastasis-free survival (MFS). We checked the consistency of the estimates for uPA and PAI-I for relapse-free survival (RFS) and MFS exploring possible sources of heterogeneity. Nodal status, the most important prognostic factor for breast cancer, introduced heterogeneity in the uPA/PAI-I survival analyses, reflecting the interaction between nodal status and uPA/PAI-I. The estimates for uPA and PAI-I were found to be consistent, even when a different transformation of their values was used. The heterogeneity of the separate data sets decreased if the levels of uPA and PAI-I were ranked, data sets were pooled, and the analyses corrected for the base model that included all traditional prognostic factors, and stratified by data set. We conclude that uPA and PAI-I are ready to be used in the clinic to help classify breast cancer patients into high and low risk groups.

الوصول الحر: https://lup.lub.lu.se/record/300732Test
http://dx.doi.org/10.1160/TH02-11-0264Test

المؤلفون: Fredstorp-Lidebring, M, Bendahl, Pär-Ola, Brunner, N, Casslén, Bertil, Högberg, Thomas, Långström-Einarsson, Eva, Willén, R, Fernö, Mårten

المصدر: European Journal of Cancer. 37(18):2339-2348

مصطلحات موضوعية: Endometrial cancer, Urokinase plasminogen activator (u-PA), Plasminogen activator inhibitor type 1 (PAI-1), DNA ploidy status, Prognosis, Medicin och hälsovetenskap, Klinisk medicin, Cancer och onkologi, Medical and Health Sciences, Clinical Medicine, Cancer and Oncology

الوصف: Components of the urokinase plasminogen activator (u-PA) system are involved in the metastatic process, and have accordingly been associated with clinical outcome in a variety of malignant tumours. We investigated the prognostic importance of u-PA and plasminogen activator inhibitor type 1 (PAI-1) in endometrial cancer, analysed with luminometric immunoassay (LIA) and enzyme-linked immunosorbent assay (ELISA), respectively. Two different cut-off levels were used: the median and the 80th percentile-the latter because of the low progression rate for patients with early stage (I-II) endometrial cancer. After a median follow-up time of 6.8 years, univariate analysis of patients with stage I-II disease (n=188) showed that high u-PA and high PAI-1 content was associated with a shorter progression-free survival (PFS), but at different cut-off levels, uPA at the median (P=0.003), and PAI-1 at the 80th percentile (P<0.001). Among the other factors, DNA ploidy status was most strongly correlated to PFS, followed by age (continuous), International Federation of Gynaecology and Obstetrics (FIGO) grade of differentiation, S-phase fraction and progesterone receptor (PgR) status. Bivariate analyses, including ploidy and one of the factors u-PA or PAI-1, showed that both add significant prognostic information. We conclude that u-PA and PAI-1 are promising prognostic factors in early stage endometrial cancer.

الوصول الحر: https://lup.lub.lu.se/record/1120946Test
http://dx.doi.org/10.1016/S0959-8049Test(01)00306-9

المؤلفون: Nielsen, H J, Christensen, I J, Brunner, N Å

المصدر: Ugeskrift for Laeger. 167(44):4163