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- Rassidakis, GZ, et al.
(författare)
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Low-level expression of SAMHD1 in acute myeloid leukemia (AML) blasts correlates with improved outcome upon consolidation chemotherapy with high-dose cytarabine-based regimens
- 2018
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Ingår i: Blood cancer journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 8:11, s. 98-
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Tidskriftsartikel (refereegranskat)abstract
- Sterile alpha motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) limits the efficacy of cytarabine (ara-C) used in AML by hydrolyzing its active metabolite ara-CTP and thus represents a promising therapeutic target. SAMHD1 has also been implicated in DNA damage repair that may impact DNA damage-inducing therapies such as anthracyclines, during induction therapy. To determine whether SAMHD1 limits ara-C efficacy during induction or consolidation therapy, SAMHD1 protein levels were assessed in two patient cohorts of de novo AML from The University of Texas MD Anderson Cancer Center (USA) and the National University Hospital (Singapore), respectively, using immunohistochemistry and tissue microarrays. SAMHD1 was expressed at a variable level by AML blasts but not in a broad range of normal hematopoietic cells in reactive bone marrows. A sizeable patient subset with low SAMHD1 expression (<25% of positive blasts) was identified, which was significantly associated with longer event-free (EFS) and overall (OS) survival in patients receiving high-dose cytarabine (HDAC) during consolidation. Therefore, evaluation of SAMHD1 expression level in AML blasts at diagnosis, may stratify patient groups for future clinical trials combining HDAC with novel SAMHD1 inhibitors as consolidation therapy.
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- Schaller, M., et al.
(författare)
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Addressing the contribution of climate and vegetation cover on hillslope denudation, Chilean Coastal Cordillera (26 degrees-38 degrees S)
- 2018
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Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 489, s. 111-122
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Tidskriftsartikel (refereegranskat)abstract
- The Earth surface is modulated by interactions among tectonics, climate, and biota. The influence of each of these factors on hillslope denudation rates is difficult to disentangle. The Chilean Coastal Cordillera offers a strong climate and vegetation gradient from arid and unvegetated in the North to humid and vegetated in the South. A similar (convergent) plate tectonic boundary lies to the West of the Coastal Cordillera. We present eight depth profiles analyzed for in situ-produced cosmogenic Be-10 in four study areas. These profiles reveal denudation rates of soil-mantled hillslopes and the depth of mobile layers. Depth profiles were investigated from both S- and N-facing mid-slope positions. Results indicate the depth of the mobile layers in the four study areas increase from N to S in latitude. When mixing is present in the mobile layers they are completely mixed. In the S- and N-facing hillslopes of each study area, mid-slope positions do not show a systematic change in depth of the mobile layers nor in denudation rates based on cosmogenic depth profiles. From N to S in latitude, modelled denudation rates of hillslopes increase from similar to 0.46 to similar to 5.65 cm/kyr and then decrease to similar to 3.22 cm/kyr in the southernmost, highest vegetation cover, study area. Calculated turnover times of soils decrease from 30 to similar to 11 kyr and then increase to similar to 22 kyr. In this work, the increasing denudation rates are attributed to increasing mean annual precipitation from N to S. However, despite the ongoing increase in precipitation from N to S, the denudation rate in the southernmost location does not continue to increase due to the protective nature of increasing vegetation cover. This indicates a vegetation induced non-linear relationship with denudation rates.
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