| 1. |
- Paulsson, Kajsa, et al.
(författare)
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High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols.
- 2013
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 98:9, s. 1424-1432
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Tidskriftsartikel (refereegranskat)abstract
- Between 1992 and 2008, 713 high hyperdiploid acute lymphoblastic leukemias in children aged 1-15 years were diagnosed and treated according to the Nordic Society for Pediatric Hematology and Oncology acute lymphoblastic leukemia 1992/2000 protocols. Twenty (2.8%) harbored t(1;19), t(9;22), der(11q23), or t(12;21). The median age was lower in the patients with 'classic' high hyperdiploidy than in those with translocation-positive high hyperdiploidy (P<0.001). Cases with triple trisomies (+4, +10, +17), comprising 50%, had higher modal numbers than the triple trisomy-negative cases (P<0.0001). The probabilities of event-free survival and overall survival were lower for those with white blood cell counts ≥50 x 109/L (P=0.017/P=0.009), ≥5% bone marrow blasts at day 29 (P=0.001/0.002), and for high risk patients (P<0.001/P=0.003), whereas event-free, but not overall, survival, was higher for cases with gains of chromosomes 4 (P<0.0001), 6 (P<0.003), 17 (P=0.010), 18 (P=0.049), and 22 (P=0.040), triple trisomies (P=0.002), and modal numbers >53/55 (P=0.020/0.024). In multivariate analyses, modal number and triple trisomies were significantly associated with superior event-free survival in separate analyses with age and white blood cell counts. When including both modal numbers and triple trisomies, only low white blood cell counts were significantly associated with superior event-free survival (P=0.009). We conclude that high modal chromosome numbers and triple trisomies are highly correlated prognostic factors and that these two parameters identify the same patient subgroup characterized by a particularly favorable outcome.
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| 2. |
- Wahlin, Björn Engelbrekt, et al.
(författare)
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T Cells in Tumors and Blood Predict Outcome in Follicular Lymphoma Treated with Rituximab
- 2011
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 17:12, s. 4136-4144
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown. EXPERIMENTAL DESIGN: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a-rituximab combinations. RESULTS: In univariate analysis, higher levels of CD3(+), CD4(+), and CD8(+) T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3(+) (P = 0.011) and blood-CD4(+) (P = 0.029) cells were independent. CD4(+) cells were favorable regardless of treatment arm, but CD8(+) cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8(+) cell levels. Higher levels of blood-CD3(+) (P = 0.003) and blood-CD4(+) (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8(+) cells longer times to next treatment (P = 0.046). CONCLUSIONS: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4(+) and CD8(+) cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8(+) cells.
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| 3. |
- Hoffner, S, et al.
(författare)
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Proficiency of drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide: the Swedish experience
- 2013
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 17:11, s. 1486-1490
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) of Mycobacterium tuberculosis against PZA is not included in the World Health Organizations yearly proficiency testing. There is an increasing need to establish quality control of PZA DST. less thanbrgreater than less thanbrgreater thanOBJECTIVE: To evaluate the performance of PZA DST and to introduce a quality assurance system for the test in Sweden. less thanbrgreater than less thanbrgreater thanMETHOD: Panels with PZA-susceptible and -resistant isolates were used in three rounds of proficiency testing in all five Swedish clinical TB laboratories and our reference laboratory. All laboratories used the MGIT 960 system. Minimum inhibitory concentrations (MICs) were determined and the pncA gene was sequenced to further characterise the 52 panel strains. less thanbrgreater than less thanbrgreater thanRESULTS: Good agreement was seen between the phenotypic PZA DST and pncA sequence data, and MIC determination confirmed high levels of resistance. However, in contrast to other drugs, for which correct proficiency test results were observed, specificity problems occurred for PZA DST in some laboratories. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: In Sweden, using panel testing, differences were seen in the proficiency of TB laboratories in correctly identifying PZA susceptibility. Improved results were noted in the third round; PZA has therefore been included in yearly proficiency testing.
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| 4. |
- Nilsson-Ehle, Herman, 1950, et al.
(författare)
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Vitaminer och spårämnen.
- 2012
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Ingår i: Laurells Klinisk kemi i praktisk medicin. - 2012 - 9., [rev. och utök.] uppl. / redaktion: Peter Nilsson-Ehle, Maria Berggren Söderlund, Elvar Theodorsson ; redaktionskommitté: Charlotte Becker, Kjell Grankvist, Anders Grubb, Göran Lindstedt, Per Simonsson.. - Lund : Studentlitteratur AB. - 9789144047874
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Bokkapitel (refereegranskat)
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| 5. |
- Gustafsson, Dan, et al.
(författare)
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Tissue zinc levels in a child with hypercalprotectinaemia and hyperzincaemia : a case report and a review of the literature
- 2012
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - London, United Kingdom : Informa Healthcare. - 0036-5513 .- 1502-7686. ; 72:1, s. 34-38
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Forskningsöversikt (refereegranskat)abstract
- Background: A girl suffering from a rare syndrome of unknown aetiology, termed hypercalprotectinaemia, was evaluated for tissue zinc status, because calprotectin is a protein which chelates Zn at multiple binding-sites, which might have affected the distribution of Zn in her body.Methods: Measurement of serum, urine, hair and nail zinc (Zn) concentration, complemented with measurement of total Zn in ultrafiltrates of plasma.Results: Her serum Zn concentration was 105-133 mu mol/L. Zn levels in her hair (102 mu g/g), nail (90 mu g/g) and urine (3-12 mu mol/L; 20-80 mu g/dL) were all at the lower end of the reference intervals described in the sparse literature. Zn concentrations in ultrafiltrates of plasma were below the detection limit (<100 nmol/L). Thus, the elevated serum Zn did not translate into a similarly increased level of Zn in any of the tissues tested, nor in free Zn concentrations. Instead it appeared to be a result of Zn being chelated to binder proteins, most probably calprotectin.Conclusion: Her grossly elevated serum calprotectin concentration is probably able to raise circulating total Zn concentrations without raising ionized concentrations, but this Zn remains confined to the circulating blood as well as to excreted body fluids, particularly faeces.
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| 6. |
- Norda, Rut, et al.
(författare)
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Complement activation products in liquid stored plasma and C3a kinetics after transfusion of autologous plasma
- 2012
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Ingår i: Vox Sanguinis. - Malden : Wiley-Blackwell. - 0042-9007 .- 1423-0410. ; 102:2, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Keeping a small stock of liquid plasma readily available for transfusion is common practise in Sweden. We report data on complement activation markers in plasma components during storage in the liquid state and the kinetics of C3a-desArg after transfusion of autologous plasma with high content of C3a-desArg.Material and Methods: Plasma components were prepared by apheresis or from whole blood. C3 fragments (C3a-desArg, C3d, g, iC3), and soluble terminal complement complex (sC5b-9) were investigated. C3a-desArg kinetics was investigated in regular apheresis donors.Results: Apheresis plasma prepared by membrane centrifugation had significantly higher level of C3a-desArg, C3d, g and sC5b-9 from day 0 and low iC3, than plasma prepared by other methods. By storage day 7, C3a-desArg -levels were above the reference value in 88% of all components. After re-infusion of autologous plasma with high C3a-desArg content, there were rapid a1 and a2-distribution followed by a slower b-elimination phase.Conclusion: Plasma components prepared by different methods and stored in the liquid phase differ significantly in the amount and timing of complement activation. C3a-desArg present in plasma is rapidly eliminated after transfusion. Autologous plasma could be used to study complement kinetics in different clinical situations.
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| 7. |
- Botling, Johan, et al.
(författare)
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Biomarker Discovery in Non-Small Cell Lung Cancer : Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation
- 2013
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:1, s. 194-204
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.
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| 8. |
- Evang, Johan Arild, et al.
(författare)
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Reduced levels of E-cadherin correlate with progression of corticotroph pituitary tumours
- 2011
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Ingår i: Clinical Endocrinology. - Oxford : Wiley. - 0300-0664 .- 1365-2265. ; 75:6, s. 811-818
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:Loss of E-cadherin is an important marker of epithelial tumour progression. The aims of this study were to explore whether E-cadherin expression and localization correlate to corticotroph tumour progression, relate the expression of the E-cadherin gene (CDH1) to immunohistochemical E-cadherin staining pattern, and study whether the E-cadherin levels were correlated to methylation status of the CDH1 promoter region.DESIGN:Immunohistochemical analyses of E-cadherin protein were performed, as was RT-qPCR of the CDH1 and the POMC genes. Methylation pattern of the promoter region of CDH1 was measured using pyrosequencing of bisulfite-treated DNA.PATIENTS:Forty-five patients operated at a tertiary referral centre in Oslo, Norway. Adenoma tissue sections and RNA samples from patients with verified Cushing's disease or Nelson's syndrome were collected.MEASUREMENTS:Expression of E-cadherin mRNA and protein in pituitary corticotroph adenomas and average percentage of methylated cytosines in a cytosine-phosphate-guanosine island of the CDH1 promoter.RESULTS:Correlations were observed between tumour progression and both nuclear expression of E-cadherin and reduced CDH1 mRNA. The E-cadherin expression was not determined by the methylation pattern of the CDH1 promoter.CONCLUSIONS:Corticotroph tumour progression was associated with reduced expression of the epithelial marker E-cadherin.
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| 9. |
- Fougner, Stine Lyngvi, et al.
(författare)
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Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly
- 2012
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Ingår i: Clinical Endocrinology. - Malden : Wiley. - 0300-0664 .- 1365-2265. ; 76:1, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT:Somatotroph adenomas have been classified into densely granulated (DG) and sparsely granulated (SG) tumours with a transitional, intermediate group. Gsp oncogenes are activating mutations in the Gsα subunit gene, found in approximately 40% of somatotroph adenomas.OBJECTIVES:To explore granulation pattern and presence of gsp oncogene in acromegaly with correlations to clinical and biochemical variables and to the effect of treatment with somatostatin analogues (SA), as well as to describe granulation pattern in adenomas with and without SA pretreatment.DESIGN/SETTINGS/PATIENTS:Seventy-eight patients with active acromegaly were included. Long-term SA efficacy was evaluated in 29 patients treated preoperatively and in ten treated postoperatively. Granulation pattern was examined, as were immunohistochemical analyses for E-cadherin and SSTR2a. Protein levels of E-cadherin and SSTR2a were measured (Western blot). Gsp mutation analysis was available for 74 adenomas.RESULTS:DG adenomas and the transitional group had higher serum levels of IGF-1 per tumour volume than SG (P = 0·009; P = 0·005). Acute and long-term SA responses were lower in SG (P = 0·001; P = 0·043). No correlation between gsp mutation and granulation was found, and no difference in granulation pattern according to preoperative SA treatment was demonstrated. A significant correlation between granulation and E-cadherin was found, where SG had lowest immunohistochemical expression, substantiated by protein levels, and a highly significant gradient was observed from DG, through the transitional group, to SG.CONCLUSIONS:Densely granulated adenomas were highly responsive to somatostatin analogues in contrast to SG adenomas. The transitional group behaved clinically more like DG adenomas. However, based on E-cadherin, a marker of dedifferentiation, the transitional group seemed to be a true intermediate.
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| 10. |
- Kashyap, Vasundhra, et al.
(författare)
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The lysine specific demethylase-1 (LSD1/KDM1A) regulates VEGF-A expression in prostate cancer
- 2013
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 7:3, s. 555-566
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Tidskriftsartikel (refereegranskat)abstract
- Recurrent prostate cancer remains a major clinical challenge. The lysine specific demethylase-1 (LSD1/KDM1A), together with the JmjC domain-containing JMJD2A and JMJD2C proteins, have emerged as critical regulators of histone lysine methylation. The LSD1-JMJD2 complex functions as a transcriptional co-regulator of hormone activated androgen and estrogen receptors at specific gene promoters. LSD1 also regulates DNA methylation and p53 function. LSD1 is overexpressed in numerous cancers including prostate cancer through an unknown mechanism. We investigated expression of the LSD1 and JMJD2A in malignant human prostate specimens. We correlated LSD1 and JMJD2A expression with known mediators of prostate cancer progression: VEGF-A and cyclin A1. We show that elevated expression of LSD1, but not JMJD2A, correlates with prostate cancer recurrence and with increased VEGF-A expression. We show that functional depletion of LSD1 expression using siRNA in prostate cancer cells decreases VEGF-A and blocks androgen induced VEGF-A, PSA and Tmprss2 expression. We demonstrate that pharmacological inhibition of LSD1 reduces proliferation of both androgen dependent (LnCaP) and independent cell lines (LnCaP: C42, PC3). We show a direct mechanistic link between LSD1 overexpression and increased activity of pro-angiogenic pathways. New therapies targeting LSD1 activity should be useful in the treatment of hormone dependent and independent prostate cancer. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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