| 1. |
- Mathsson, Linda, et al.
(författare)
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Cryoglobulin-induced cytokine production via FcgammaRIIa: inverse effects of complement blockade on the production of TNF-alpha and IL-10. Implications for the growth of malignant B-cell clones.
- 2005
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Ingår i: British Journal of Haematology. ; 129:6, s. 830-838
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies produced by patients with lymphoproliferative diseases sometimes appear as cryoglobulins (CG), immunoglobulins (Ig) that reversibly agglutinate and form immune complexes (IC) when cooled below normal body temperature or through variation in pH and ionic strength. In accordance with our findings of IC-induced cytokine production from peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus, we investigated whether CG can also induce cytokine production. One IgG and one IgM type I CG from two patients with multiple myeloma and Waldenstrom's macroglobulinaemia were individually purified and added to PBMC cultures. In separate experiments temperature and ionic strength were varied, or FcgammaRIIa, FcgammaRIII and complement activation were blocked; supernatant cytokine levels were then determined by enzyme-linked immunosorbent assay. CG-induced cytokine production from monocytes varied with precipitation induced by changes in temperature and ionic strength and was mediated via FcRIIa- and complement-dependent mechanisms. Complement blockade resulted in increased IgG CG-induced interleukin (IL)-10 production that was inversely correlated with decreased production of tumour necrosis factor-alpha. CG-induced IL-10 might be a growth factor for malignant B-lymphocytes in CG-associated lymphoproliferative diseases with constant complement consumption. Knowledge of mechanisms underlying CG-induced cytokine production can be useful for designing treatments for type I CG-associated pathology in lymphoproliferative diseases.
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| 2. |
- Wiberg, Kristina, et al.
(författare)
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In vitro activity of bortezomib in cultures of patient tumour cells-potential utility in haematological malignancies
- 2009
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 26:2, s. 193-201
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Tidskriftsartikel (refereegranskat)abstract
- Bortezomib represents a new class of anti-cancer drugs, the proteasome inhibitors. We evaluated the in vitro activity of bortezomib with regard to tumour-type specificity and possible mechanisms of drug resistance in 115 samples of tumour cells from patients and in a cell-line panel, using the short-term fluorometric microculture cytotoxicity assay. Bortezomib generally showed dose-response curves with a steep slope. In patient cells, bortezomib was more active in haematological than in solid tumour samples. Myeloma and chronic myeloid leukaemia were the most sensitive tumour types although with great variability in drug response between the individual samples. Colorectal and kidney cancer samples were the least sensitive. In the cell-line panel, only small differences in response were seen between the different cell lines, and the proteasome inhibitors, lactacystin and MG 262, showed an activity pattern similar to that of bortezomib. The cell-line data suggest that resistance to bortezomib was not mediated by MRP-, PgP, GSH-; tubulin and topo II-associated MDR. Combination experiments indicated synergy between bortezomib and arsenic trioxide or irinotecan. The data support the current use of bortezomib but also points to its potential utility in other tumour types and in combination with cytotoxic drugs.
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| 5. |
- Lenhoff, Stig, et al.
(författare)
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Intensive therapy for multiple myeloma in patients younger than 60 years. Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation
- 2006
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Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 91:9, s. 1228-1233
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives. From 1994 to 1997 we conducted a population-based, prospective study on intensive therapy in newly diagnosed symptomatic myeloma patients younger than 60 years, comparing their survival to that of a conventionally treated historic population. Long-term results are presented, including the impact of the degree of response on survival and relapse pattern after transplantation. Design and Methods. The prospective population was formed of 397 patients and the historic population of 313 patients. Both populations were calculated to comprise more than 75% of the expected number of new cases. Results. After a median follow-up of 7 years survival was longer in the prospective population than in the historic one (median 60 versus 39 months; p=0.0002). When comparing only patients eligible for intensive therapy the median survival was 63 versus 44 months (p < 0.0001). Attaining a complete response was associated with prolonged event-free survival but not overall survival. The pattern of relapse after transplantation was heterogeneous but could be divided into four major groups; insidious, classical, plasmacytoma form and transformed disease. The median survival after relapse was 29 months. The relapse pattern and time to relapse predicted outcome. Patients relapsing with an insidious or classical form of disease with skeletal events only, or after a long lasting first response were likely to respond well to conventional salvage therapy. In contrast, relapse with multiple symptoms, transformed disease or a short duration of first response implied bad prognosis. Interpretation and conclusions. The relapse pattern after autologous transplantation is heterogeneous and response to salvage therapy is variable. The degree of response and event-free survival after transplantation are not reliable surrogate markers for survival.
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| 6. |
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| 7. |
- Saxena, Richa, et al.
(författare)
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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
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Tidskriftsartikel (refereegranskat)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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| 8. |
- Strömberg, Thomas, et al.
(författare)
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IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells.
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 107:2, s. 669-78
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests the insulin-like growth factor-1 receptor (IGF-1R) to be an important mediator of tumor-cell survival and resistance to cytotoxic therapy in multiple myeloma (MM). Recently, members of the cyclolignan family have been shown to selectively inhibit the receptor tyrosine kinase (RTK) activity of the IGF-1R beta-chain. The effects of the cyclolignan picropodophyllin (PPP) were studied in vitro using a panel of 13 MM cell lines and freshly purified tumor cells from 10 patients with MM. PPP clearly inhibited growth in all MM cell lines and primary MM samples cultured in the presence or absence of bone marrow stromal cells. PPP induced a profound accumulation of cells in the G(2)/M-phase and an increased apoptosis. Importantly, IGF-1, IGF-2, insulin, or IL-6 did not reduce the inhibitory effects of PPP. As demonstrated by in vitro kinase assays, PPP down-regulated the IGF-1 RTK activity without inhibiting the insulin RTK activity. This conferred decreased phosphorylation of Erk1/2 and reduced cyclin dependent kinase (CDK1) activity. In addition, the expression of mcl-1 and survivin was reduced. Taken together, we suggest that interfering with the IGF-1 RTK by using the cyclolignan PPP offers a novel and selective therapeutic strategy for MM.
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| 9. |
- Wärmefjord, Kristina, 1976, et al.
(författare)
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A Measure of the Information Loss for Inspection Point Reduction
- 2008
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Ingår i: ASME 2008 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference, IDETC/CIE2008; Brooklyn, NY; United States; 3 August 2008 through 6 August 2008. - 9780791843253 ; 1:PARTS A AND B, s. 693-700
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Konferensbidrag (refereegranskat)abstract
- Since the vehicle program in automotive industry gets more and more extensive, the costs related to inspection increase. Therefore, there are needs for more effective inspection preparation. In many situations, a large number of inspection points are measured, despite the fact that only a small subset of points is needed. A method, based on cluster analysis, for identifying redundant inspection points has earlier been successfully tested on industrial cases. Cluster analysis is used for grouping the variables into clusters, where the points in each cluster are highly correlated. From every cluster only one representing point is selected for inspection. In this paper the method is further developed and multiple linear regression is used for evaluating how much of the information that is lost when discarding an inspection point. The information loss can be quantified using an efficiency measure based on linear multiple regression, where the part of the variation in the discarded variables that can be explained by the remaining variables is calculated. This measure can be illustrated graphically and that helps to decide how many clusters that should be formed, i.e. how many inspection points that can be discarded.
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| 10. |
- Wärmefjord, Kristina, 1976, et al.
(författare)
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A Measure of the Information Loss for Inspection Point Reduction
- 2009
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Ingår i: Journal of Manufacturing Science and Engineering, Transactions of the ASME. - : ASME International. - 1087-1357 .- 1528-8935. ; 131:5, s. 0510171-0510176
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Tidskriftsartikel (refereegranskat)abstract
- Since the vehicle program in the automotive industry gets more and more extensive, the costs related to inspection increase. Therefore, there are needs for more effective inspection preparation. In many situations, a large number of inspection points are measured, despite the fact that only a small subset of points is needed. A method, based on cluster analysis, for identifying redundant inspection points has earlier been successfully tested on industrial cases. Cluster analysis is used for grouping the variables into clusters, where the points in each cluster are highly correlated. From every cluster only one representing point is selected for inspection. In this paper the method is further developed, and multiple linear regression is used for evaluating how much of the information is lost when discarding an inspection point. The information loss can be quantified using an efficiency measure based on linear multiple regression, where the part of the variation in the discarded variables that can be explained by the remaining variables is calculated. This measure can be illustrated graphically and that helps to decide how many clusters that should be formed, i.e., how many inspection points that can be discarded.
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