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Sökning: WFRF:(Swinkels Dorine W)

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1.
  • Engert, Andreas, et al. (författare)
  • The European Hematology Association Roadmap for European Hematology Research : a consensus document
  • 2016
  • Ingår i: Haematologica. - Pavia, Italy : Fondazione Ferrata Storti. - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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3.
  • Coenen, Marieke J H, et al. (författare)
  • Genetic Variants in Toll-Like Receptors Are Not Associated with Rheumatoid Arthritis Susceptibility or Anti-Tumour Necrosis Factor Treatment Outcome
  • 2010
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication. Methodology and Principal Findings: 22 single nucleotide polymorphisms (SNPs) in seven TLR genes were genotyped in a Dutch cohort consisting of 378 RA patients and 294 controls. Significantly associated variants were investigated in replication cohorts from The Netherlands, United Kingdom and Sweden (2877 RA patients and 2025 controls). 182 of the Dutch patients were treated with anti-TNF medication. Using these patients and a replication cohort (269 Swedish patients) we analysed if genetic variants in TLR genes were associated with anti-TNF outcome. In the discovery phase of the study we found a significant association of SNPs rs2072493 in TLR5 and rs3853839 in TLR7 with RA disease susceptibility. Meta-analysis of discovery and replication cohorts did not confirm these findings. SNP rs2072493 in TLR5 was associated with anti-TNF outcome in the Dutch but not in the Swedish population. Conclusion: We conclude that genetic variants in TLRs do not play a major role in susceptibility for developing RA nor in anti-TNF treatment outcome in a Caucasian population.
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4.
  • Schultz, Iman J, et al. (författare)
  • Gene expression analysis for the prediction of recurrence in patients with primary Ta urothelial cell carcinoma
  • 2007
  • Ingår i: European Urology. - 0302-2838 .- 1873-7560. ; 51:2, s. 416-423
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The individual recurrence-free period after primary surgery of patients with Ta urothelial cell carcinoma (UCC) cannot be predicted accurately. This study aims at discriminating between patients with primary Ta UCC and long or short recurrence-free periods. Methods We investigated mRNA expression of 23 genes in 44 primary Ta tumours (23 and 21 tumours were from patients with long [≥4 yr] or short [≤2 yr] recurrence-free periods, respectively), using real-time quantitative polymerase chain reaction. The genes were selected from previously published studies and showed a relationship with tumour recurrence in patients with UCC. Results Differential mRNA expression between the two patient groups indicated statistical significance only for the gene survivin (p = 0.0011). Its recurrence predictive value could not be increased by a combination with any of the other genes. Comparison of the receiver operating characteristic curves for survivin expression between patients with long or short recurrence-free intervals revealed an area under the curve of 0.79 (95%CI, 0.65–0.92). Using the median expression (0.84) as cut-off level, survivin identified 71.4% (95%CI, 47.8–88.7) and 69.6% (95%CI, 47.1–86.8) of the patients with long or short recurrence-free periods, respectively. Conclusions Our study identifies survivin as the most promising candidate to distinguish between patients with primary Ta UCC and long or short recurrence-free intervals. Therefore, survivin mRNA expression analysis might help the urologist to individualise patient treatment and prevent unnecessary cystoscopies in a subgroup of these patients.
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5.
  • Schultz, Iman J., et al. (författare)
  • Prediction of recurrence in Ta urothelial cell carcinoma by real-time quantitative PCR analysis : a microarray validation study
  • 2006
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 119:8, s. 1915-1919
  • Tidskriftsartikel (refereegranskat)abstract
    • Accurate prediction of tumor recurrence in patients with superficial urothelial cell carcinoma (UCC) might result in a significant reduction of invasive follow-up cystoscopies. A recent study identified a panel of 26 genes from a large cDNA microarray analysis of bladder tumors that discriminated between early- and late-recurring patients with superficial Ta tumors (Dyrskjot et al., Nat Genet 2003;33:90-6). We aimed to validate this panel of genes in 44 primary Ta UCCs (23 and 21 tumors from patients with short or prolonged recurrence-free periods, respectively), by real-time quantitative PCR. Statistical analysis showed marginal significant different mRNA expression levels between the 2 patient groups. To evaluate a supplementary effect of genes for the identification of patients with short or prolonged recurrence-free intervals, forward logistic regression analysis was applied. This revealed that a combination of the expression profiles of the genes HNRPK, LTB4DH and ANP32B resulted in the best performance, although the combination only marginally increased the predictive value of HNRPK alone. Comparing the receiver-operating-characteristic curves for HNRPK expression among patients with short or prolonged recurrence-free periods, revealed an area under the curve of 0.696 (95% CI, 0.537-0.855). Using the median HNRPK expression level as cut-off, a sensitivity of 69.6% and a specificity of 71.4% were obtained for the identification of patients with short or prolonged recurrence-free periods, respectively. In conclusion, we were not able to confirm the microarray gene expression pattern of the 26 genes shown by Dyrskjot et al. The discovery of accurate recurrence predictive markers, therefore, remains a challenge.
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6.
  • Schultz, Iman J., et al. (författare)
  • Simultaneous proteomic and genomic analysis of primary Ta urothelial cell carcinomas for the prediction of tumor recurrence
  • 2007
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:2, s. 1051-1058
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prediction of tumor recurrence in patients with Ta urothelial cell carcinoma is inaccurate and new prognostic markers are desirable. Materials and Methods: Surface-enhanced laser-desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) was performed on 33 primary Ta tumors (16 and 17 tumors were from patients with long and short recurrence-free periods, respectively) and data were compared to previously obtained mRNA expression profiles of 49 genes. Results: The intensities of a protein peak at m/z 33331 varied most significantly between the two patient groups (p=0.0048). This was comparable to survivin, whose mRNA expression differed most significantly (p=0.0042) of the 49 genes. ROC analysis revealed an area under the curve for protein peak 33331 and survivin of 0.78 (95% CI, 0.62-0.94) and 0.79 (95% CI, 0.63-0.94), respectively. Protein peak 33331 and survivin identified 3 (17%) and 8 (47%) patients with a recurrence-free period of at least 4 years, respectively, without generating false-negatives. Conclusion: These findings indicate that SELDI-TOF MS and real-time Q-PCR analysis on the same tissue can result in the identification of markers with comparable differential expression. Such combined analyses may yield combinations of several markers that might improve disease prognosis.
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7.
  • Schultz, Iman J., et al. (författare)
  • The Prognostic Role of the STK15 T91A Polymorphism and of STK15 mRNA Expression in Patients with Urothelial Cell Carcinoma
  • 2007
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:2, s. 1025-1030
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prognostic role of the STK15 T91A polymorphism and of STK15 mRNA expression was investigated in patients with urothelial cell carcinoma (UCC). Materials and Methods: The STK15 genotype with respect to the T91A polymorphism was assessed by restriction fragment length polymorphism in 135 patients. STK15 mRNA expression was measured in tumor tissues of 103 patients, using real-time quantitative PCR. Results: The T91A polymorphism lacked any prognostic information in our patient cohort. Interestingly though, STK15 mRNA expression was increased in invasive and high-grade tumors (p-values of 0.009 and 0.0001, respectively). Additionally, patients with superficial UCC (n=82) who had a tumor recurrence in the first year after surgery displayed elevated STK15 mRNA expression levels (p=0.009). Kaplan-Meier survival analysis revealed an increased risk of tumor progression for patients with Ta tumors (n=62) and high STK15 expression (log-rank p=0.04). Furthermore, a decreased overall (log-rank p=0.006) and UCC-specific survival (log-rank p=0.001) were shown for patients with elevated STK15 mRNA levels. Conclusion: Patients with UCC and elevated levels of STK15 mRNA generally showed a more adverse disease course than patients with low levels. This may help in identifying patients in need of more aggressive treatment.
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8.
  • Uljterschout, Lieke, et al. (författare)
  • Serum hepcidin measured by immunochemical and mass-spectrometric methods and their correlation with iron status indicators in healthy children aged 0.5-3 y
  • 2014
  • Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 76:4, s. 409-414
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The diagnostic use of hepcidin is limited by the absence of standardization and lack of age-specific reference ranges in children in particular. The aim of this study was to determine reference ranges of serum hepcidin in healthy children aged 0.5-3 y using mass spectometry (MS) and a commercial immunochemical (IC) assay, and to investigate its association with other indicators of iron status and inflammation. METHODS: We included 400 healthy children aged 0.5-3 y. We constructed reference ranges for MS-hepcidin and IC-hepcidin concentrations using the median, P2.5, and P97.5 in a normative population of 219 children with no anemia, no infection and/or inflammation, and no iron deficiency. RESULTS: Median concentrations (P2.5-P97.5) of MS-hepcidin and IC-hepcidin were 3.6 nmol/l (0.6-13.9 nmol/l) and 7.9 nmol/l (1.9-28.6 nmol/l), respectively. We found a good correlation between both methods. However, MS-hepcidin was consistently lower than IC-hepcidin. Hepcidin correlated with ferritin and C-reactive protein. CONCLUSION: We provide reference ranges for hepcidin for an MS and commercial IC method. Absolute values between assays differed significantly, but hepcidin concentrations obtained by MS and IC methods correlate with each other, and both correlate with ferritin and CRP.
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