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1.
  • Frost, Britt-Marie, et al. (författare)
  • Increased <em>in vitro</em> cellular drug resistance is related to poor outcome in high-risk childhood acute lymphoblastic leukaemia
  • 2003
  • Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 122:3, s. 376-385
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Summary.</strong> We determined the <em>in vitro</em> cellular drug resistance in 370 children with newly diagnosed acute lymphoblastic leukaemia (ALL). The resistance to each of 10 drugs was measured by the fluorometric microculture cytotoxicity assay (FMCA) and was related to clinical outcome. The median follow-up time was 41 months. Risk-group stratified analyses indicated that <em>in vitro</em> resistance to dexamethasone, doxorubicin and amsacrine were each significantly related to the probability of disease-free survival. In the high-risk (HR) group, increased <em>in vitro</em> resistance to dexamethasone (<em>P</em> = 0·014), etoposide (<em>P</em> = 0·025) and doxorubicin (<em>P</em> = 0·05) was associated with a worse clinical outcome. Combining the results for these drugs provided a drug resistance score with an independent prognostic significance superior to that of any other factor studied, with a relative risk of relapse in the most resistant group 9·8 times that in the most sensitive group (<em>P</em> = 0·007). The results in the intermediate-risk (IR) and standard-risk (SR) groups were less clear cut. In conclusion, our data indicate that <em>in vitro</em> testing of cellular drug resistance can be used to predict the clinical outcome in HR ALL, while the final evaluation of the results in IR and SR patients must await longer follow-up.</p>
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2.
  • Roehle, Anja, et al. (författare)
  • MicroRNA signatures characterize diffuse large B-cell lymphomas and follicular lymphomas
  • 2008
  • Ingår i: British Journal of Haematology. - Hoboken, USA : Wiley-Blackwell. - 0007-1048 .- 1365-2141. ; 142:5, s. 732-44
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>MicroRNAs (miRNA, miR) are negative regulators of gene expression that play an important role in diverse biological processes such as development, cell growth, apoptosis and haematopoiesis, suggesting their association with cancer. Here we analysed the expression signatures of 157 miRNAs in 58 diffuse large B-cell lymphoma (DLBCL), 46 follicular lymphoma (FL) and seven non-neoplastic lymph nodes (LN). Comparison of the possible combinations of DLBCL-, FL- and LN resulted in specific DLBCL- and FL-signatures, which include miRNAs with previously published function in haematopoiesis (MIRN150 and MIRN155) or tumour development (MIRN210, MIRN10A, MIRN17-5P and MIRN145). As compared to LN, some miRNAs are differentially regulated in both lymphoma types (MIRN155, MIRN210, MIRN106A, MIRN149 and MIRN139). Conversely, some miRNAs show lymphoma-specific aberrant expression, such as MIRN9/9*, MIRN301, MIRN338 and MIRN213 in FL and MIRN150, MIRN17-5P, MIRN145, MIRN328 and others in DLBCL. A classification tree was computed using four miRNAs (MIRN330, MIRN17-5P, MIRN106a and MIRN210) to correctly identify 98% of all 111 cases that were analysed in this study. Finally, eight miRNAs were found to correlate with event-free and overall survival in DLBCL including known tumour suppressors (MIRN21, MIRN127 and MIRN34a) and oncogenes (MIRN195 and MIRNLET7G).</p>
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3.
  • Andersen, Mette K., et al. (författare)
  • Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13) : clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols
  • 2011
  • Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 155:2, s. 235-243
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The translocation t(1;19)(q23;p13)/der(19) t(1;19) is a risk stratifying aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19) t(1;19)-positive BCP ALL treated on two successive Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007 and have reviewed the clinical and cytogenetic characteristics of these cases, comprising 1.8% of all cases. The translocation was balanced in 15 cases (32%) and unbalanced in 29 cases (62%). The most common additional chromosome abnormalities were del(9p), i(9q), del(6q), and del(13q). The median age was 7 years, the median white blood cell (WBC) count was 16 x 10(9)/l, and the female/male ratio was 1.2. The predicted event-free survival (EFS) at 5 and 10 years was 0.79, whereas the predicted overall survival (OS) at 5 and 10 years was 0.85 and 0.82, respectively. Nine patients had a bone marrow relapse after a median of 23 months; no patient had a central nervous system relapse. Additional cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was balanced or unbalanced did not influence EFS or OS. Compared to cases with t(12,21) and high hyperdiploidy, EFS was similar, but overall survival was worse in patients with t(1;19)/der(19) t(1;19) (P = 0.004).</p>
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4.
  • Andersen, Mette K., et al. (författare)
  • Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13) : clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols
  • 2011
  • Ingår i: British Journal of Haematology. - Oxford : Blackwell Scientific. - 0007-1048 .- 1365-2141. ; 155:2, s. 235-243
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The translocation t(1;19)(q23;p13)/der(19) t(1;19) is a risk stratifying aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19) t(1;19)-positive BCP ALL treated on two successive Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007 and have reviewed the clinical and cytogenetic characteristics of these cases, comprising 1.8% of all cases. The translocation was balanced in 15 cases (32%) and unbalanced in 29 cases (62%). The most common additional chromosome abnormalities were del(9p), i(9q), del(6q), and del(13q). The median age was 7 years, the median white blood cell (WBC) count was 16 x 10(9)/l, and the female/male ratio was 1.2. The predicted event-free survival (EFS) at 5 and 10 years was 0.79, whereas the predicted overall survival (OS) at 5 and 10 years was 0.85 and 0.82, respectively. Nine patients had a bone marrow relapse after a median of 23 months; no patient had a central nervous system relapse. Additional cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was balanced or unbalanced did not influence EFS or OS. Compared to cases with t(12,21) and high hyperdiploidy, EFS was similar, but overall survival was worse in patients with t(1;19)/der(19) t(1;19) (P = 0.004).</p>
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7.
  • Axdorph, Ulla, et al. (författare)
  • Intensive chemotherapy in patients with chronic myelogenous leukaemia (CML) in accelerated or blastic phase - A report from the Swedish CML Group
  • 2002
  • Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 118:4, s. 1048-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>In attempting to restore the chronic phase (CP) of chronic myelogenous leukaemia (CML), the Swedish CML group utilized an intensive chemotherapy protocol for 83 patients (aged 16-79 years) in accelerated (AP, n = 22) or blastic phase (BC, n = 61). Most patients received a combination of mitoxantrone (12 mg/m2/d) and etoposide (100 mg/m2/d) together with cytosine arabinoside (1 g/m2 b.i.d) for 4 d. Overall, 39 patients (47%) achieved a second CP (CP2)/partial remission (PR). Responding patients <65 years were eligible for ablative chemotherapy followed by an allogeneic (SCT) or a double autologous stem cell transplant (ASCT). Seventeen of 34 responders <65 years failed to proceed to transplantation as a result of early disease progression (n = 15) or disease-related complications (n = 2). The remaining 17 patients underwent SCT (n = 9, including four unrelated donor SCT) or ASCT (n = 8). Only one of the eight ASCT patients had a second ASCT, the remaining seven failed because of progression (n = 5) or hypoplasia (n = 2). The median duration of CP2/PR was 6 months (range 1-72 months). Five patients achieved a longer CP2/PR than CP1. The 1 year survival was 70% for SCT/ASCT patients (median survival 21 months), 50% for responding patients overall, but only 7% for non-responders (P < 0.001). Three SCT/ASCT patients are long-term survivors (65+, 66+ and 73+ months). In conclusion, approximately half of the patients achieved a CP2/PR after intensive chemotherapy, with a clear survival advantage for responders vs non-responders. Subsequent SCT/ASCT was feasible for half of the responders (<65 years), and one individual underwent double ASCT. Novel therapeutic options for CML patients in AP/BP are needed.</p>
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8.
  • Baecklund, Eva, et al. (författare)
  • Expression of the human germinal-centre-associated lymphoma protein in diffuse large B-cell lymphomas in patients with rheumatoid arthritis
  • 2008
  • Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 141:1, s. 69-72
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Diffuse large B-cell lymphomas (DLBCL) can be subdivided into germinal centre (GC)-like and non-GC-like subtypes by CD10, BCL6 and MUM1/IRF4 status. We previously reported that patients with severe rheumatoid arthritis (RA) are at increased risk of non-GC DLBCL. This study examined a new GC-marker, human germinal-centre-associated lymphoma (HGAL) protein, in RA-DLBCL. Of 111, 38 (34%) DLBCL were HGAL-positive and showed less disseminated disease and a tendency toward improved overall survival compared to HGAL-negative cases. This supports that a majority of RA-DLBCL are of non-GC origin, indicating a specific role for activated peripheral B cells in the pathogenesis of RA-DLBCL.</p>
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10.
  • Beshara, Soheir, et al. (författare)
  • Kinetic analysis of 52Fe-labelled iron(III) hydroxide-sucrose complex following bolus administration using positron emission tomography
  • 1999
  • Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 104:2, s. 288-295
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Kinetic analysis of a single intravenous injection of 100 mg iron(III) hydroxide-sucrose complex (Venofer) mixed with 52Fe(III) hydroxide-sucrose as a tracer was followed for 3-6 h in four generally anaesthetized, artificially ventilated minipigs using positron emission tomography (PET). The amount of injected radioactivity ranged from 30 to 200 MBq. Blood radioactivity, measured by PET in the left ventricle of the heart, displayed a fast clearance phase followed by a slow one. In the liver and bone marrow a fast radioactivity uptake occurred during the first 30 min, followed by a slower steady increase. In the liver a slight decrease in radioactivity uptake was noted by the end of the study. A kinetic analysis using a three-compartment (namely blood pool, reversible and irreversible tissue pools) model showed a fairly high distribution volume in the liver as compared with the bone marrow. In conclusion, the pharmacokinetics of the injected complex was clearly visualized with the PET technique. The organs of particular interest, namely the heart (for blood kinetics), liver and bone marrow could all be viewed by a single setting of a PET tomograph with an axial field of view of 10 cm. The half-life (T1/2) of 52Fe (8.3 h) enables a detailed kinetic study up to 24 h. A novel method was introduced to verify the actual 52Fe contribution to the PET images by removing the interfering radioactive daughter 52mMn positron emissions. The kinetic data fitted the three-compartment model, from which rate constants could be obtained for iron transfer from the blood to a pool of iron in bone marrow or liver to which it was bound during the study period. In addition, there was a reversible tissue pool of iron, which in the liver slowly equilibrated with the blood, to give a net efflux from the liver some hours after i.v. administration. The liver uptake showed a relatively long distribution phase, whereas the injected iron was immediately incorporated into the bone marrow. Various transport mechanisms seem to be involved in the handling of the injected iron complex.</p>
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