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- Schmiegelow, K, et al.
(författare)
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The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse.
- 2010
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 24:4, s. 715-20
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Tidskriftsartikel (refereegranskat)abstract
- Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (>or=10 years) and 176 non-adolescents (<10 years) with B-cell precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC) <50 x 10(9)/l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS(12y):0.71 vs 0.83, P=0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (r(S)=0.36, P=0.02), which became nonsignificant for those who relapsed (r(S)=0.05, P=0.9). The best-fit multivariate Cox regression model to predict risk of relapse included mWBC and thiopurine methyltransferase activity, which methylates mercaptopurine and reduces the intracellular availability of cytotoxic 6-thioguanine nucleotides (coefficient: 0.11, P=0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient=0.65, P=0.003) than for non-adolescents (coefficient=0.42, P=0.04). Adolescents had higher mean neutrophil counts (P=0.002) than non-adolescents, but received nonsignificantly lower mercaptopurine and MTX doses during maintenance therapy. Red blood cell MTX levels were significantly related to the dose of MTX among adolescents who stayed in remission (r(S)=0.38, P=0.02), which was not the case for those who developed a relapse (r(S)=0.15, P=0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL.
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| 5. |
- Buentke, E, et al.
(författare)
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Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells
- 2011
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Ingår i: Blood Cancer Journal. - : Macmillan Publishers Limited. - 2044-5385. ; 1:e31, s. 9-
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Tidskriftsartikel (refereegranskat)abstract
- Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs.
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| 8. |
- Keune, H., et al.
(författare)
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Science-policy challenges for biodiversity, public health and urbanization : examples from Belgium
- 2013
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 8:2, s. 025015-
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Tidskriftsartikel (refereegranskat)abstract
- Internationally, the importance of a coordinated effort to protect both biodiversity and public health is more and more recognized. These issues are often concentrated or particularly challenging in urban areas, and therefore on-going urbanization worldwide raises particular issues both for the conservation of living natural resources and for population health strategies. These challenges include significant difficulties associated with sustainable management of urban ecosystems, urban development planning, social cohesion and public health. An important element of the challenge is the need to interface between different forms of knowledge and different actors from science and policy. We illustrate this with examples from Belgium, showcasing concrete cases of human-nature interaction. To better tackle these challenges, since 2011, actors in science, policy and the broader Belgian society have launched a number of initiatives to deal in a more integrated manner with combined biodiversity and public health challenges in the face of ongoing urbanization. This emerging community of practice in Belgium exemplifies the importance of interfacing at different levels. (1) Bridges must be built between science and the complex biodiversity/ecosystem-human/public health-urbanization phenomena. (2) Bridges between different professional communities and disciplines are urgently needed. (3) Closer collaboration between science and policy, and between science and societal practice is needed. Moreover, within each of these communities closer collaboration between specialized sections is needed.
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