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- Lakiotaki, E, et al.
(författare)
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Potential role of AKT/mTOR signalling proteins in hairy cell leukaemia: association with BRAF/ERK activation and clinical outcome
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 21252-
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Tidskriftsartikel (refereegranskat)abstract
- The potential role of AKT/mTOR signalling proteins and its association with the Raf-MEK-ERK pathway was investigated in hairy cell leukaemia (HCL). BRAFV600E expression and activated forms of AKT, mTOR, ERK1/2, p70S6k and 4E-BP1 were immunohistochemically assessed in 77 BM biopsies of HCL patients and correlated with clinicopathological and BM microvascular characteristics, as well as with c-Caspase-3 levels in hairy cells. Additionally, we tested rapamycin treatment response of BONNA-12 wild-type cells or transfected with BRAFV600E. Most HCL cases expressed p-p70S6K and p-4E-BP1 but not p-mTOR, being accompanied by p-ERK1/2 and p-AKT. AKT/mTOR activation was evident in BONNA-12 cells irrespective of the presence of BRAFV600E mutation and was implicated in cell proliferation enhancement. In multivariate analysis p-AKT/p-mTOR/p-4E-BP1 overexpression was an adverse prognostic factor for time to next treatment conferring earlier relapse. When p-AKT, p-mTOR and p-4E-BP1 were examined separately only p-4E-BP1 remained significant. Our findings indicate that in HCL, critical proteins up- and downstream of mTOR are activated. Moreover, the strong associations with Raf-MEK-ERK signalling imply a possible biologic interaction between these pathways. Most importantly, expression of p-4E-BP1 alone or combined with p-AKT and p-mTOR is of prognostic value in patients with HCL.
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| 3. |
- Ntaios, G, et al.
(författare)
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Small-vessel occlusion versus large-artery atherosclerotic strokes in diabetics: Patient characteristics, outcomes, and predictors of stroke mechanism
- 2016
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 1:2, s. 108-113
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Introduction: Diabetes mellitus exerts a detrimental effect on cerebral vasculature affecting both macrovasculature and microvasculature. However, although ischaemic stroke is typically included among macrovascular diabetic complications, it is frequently omitted from microvascular diabetic complications. We aimed to compare the proportion of large-artery atherosclerotic and small-vessel occlusion strokes among diabetic stroke patients, explore their differences and outcomes, and assess potential mechanisms which may determine why some diabetic patients suffer large-artery atherosclerotic stroke whereas others suffer small-vessel occlusion stroke. Methods: We pooled data of diabetic patients from four prospective ischaemic stroke registries (Acute Stroke Registry and Analysis of Lausanne (ASTRAL), Athens, Austrian, and Helsinki Stroke Thrombolysis Registries). Stroke severity and prognosis were assessed with National Institutes of Health Stroke Scale (NIHSS) and ASTRAL scores, respectively; functional outcome with three-month modified Rankin score (0–2 considered as favourable outcome). Logistic- regression analysis identified independent predictors of large-artery atherosclerotic stroke. Results: Among 5412 patients, 1069 (19.8%) were diabetics; of them, 232 (21.7%) had large-artery atherosclerotic and 205 (19.2%) small-vessel occlusion strokes. Large-artery atherosclerotic stroke had higher severity than small-vessel occlusion stroke (median NIHSS: 6 vs. 3, p < 0.001), worse prognosis (median ASTRAL score: 23 vs. 19, p < 0.001), and worse three-month outcome (60.3% vs. 83.4% with favourable outcome, p < 0.001). In logistic-regression analysis, peripheral artery disease (odds ratio: 4.013, 95% confidence interval: 1.667–9.665, p < 0.01) and smoking (odds ratio: 1.706, 95% confidence interval: 1.087–2.675, p < 0.05) were independently associated with large-artery atherosclerotic strokes. Conclusion: In the diabetic stroke population, small-vessel occlusion and large-artery atherosclerotic strokes occur with similar frequency. Large-artery atherosclerotic strokes are more severe and have worse outcome than small-vessel occlusion strokes. The presence of peripheral artery disease and smoking independently predicted large-artery athero- sclerotic stroke.
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