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- Jashari, Haki, et al.
(författare)
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Coarctation repair normalizes left ventricular function and aorto-septal angle in neonates
- 2017
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Ingår i: Congenital Heart Disease. - : Computers, Materials and Continua (Tech Science Press). - 1747-079X .- 1747-0803. ; 12:2, s. 218-225
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Patients with coarctation of the aorta (CoA) have increased left ventricular (LV) afterload that has been shown to impact the LV and ascending aortic function. We aimed to examine the effect of coarctation on LV function and aorto-septal angle (AoSA) before and after surgical repair.Methods: We retrospectively studied 21 patients with surgically repaired CoA at a median age of 9 (2-53) days at three time points: (1) just before intervention, (2) at short-term follow-up, and (3) at medium-term follow-up after intervention. AoSA was measured from the parasternal long axisview, at three time points during the cardiac cycle: (1) end diastole, (2) beginning of systole, and (3) at peak ejection in the descending aorta. In addition to conventional LV structure and function, global longitudinal strain, and strain rate were measured using STE technique and Tomtec soft-ware. Three groups of age matched healthy children served as controls at each time point.Results: AoSA was significantly wider before intervention, in particular at peak ejection in the descending aorta (1448 6 6.48 vs. 1368 6 4.18; P < .0001), and correlated with CoA pressure gradi-ent. After intervention, AoSA normalized and significantly correlated with the increase of LV cavity function and overall LV deformation parameters.Conclusions: AoSA is abnormally wide in neonates with CoA and is associated with severity ofobstruction, LV dysfunction and compromised LV global deformation.
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| 2. |
- Tesan, Tajana, 1977, et al.
(författare)
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A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aims of this study were to characterize the genetic alterations underlying the development of PA in six tumor cases, and evaluate methods for fusion oncogene detection. Using a combined analysis of RNA sequencing and copy number variation data we identified a new BRAF fusion involving the 5' gene fusion partner GTF2I (7q11.23), not previously described in PA. The new GTF2I-BRAF 19-10 fusion was found in one case, while the other five cases harbored the frequent KIAA1549-BRAF 16-9 fusion gene. Similar to other BRAF fusions, the GTF2I-BRAF fusion retains an intact BRAF kinase domain while the inhibitory N-terminal domain is lost. Functional studies on GTF2I-BRAF showed elevated MAPK pathway activation compared to BRAF WT. Comparing fusion detection methods, we found Fluorescence in situ hybridization with BRAF break apart probe as the most sensitive method for detection of different BRAF rearrangements (GTF2I-BRAF and KIAA1549-BRAF). Our finding of a new BRAF fusion in PA further emphasis the important role of B-Raf in tumorigenesis of these tumor types. Moreover, the consistency and growing list of BRAF/RAF gene fusions suggests these rearrangements to be informative tumor markers in molecular diagnostics, which could guide future treatment strategies.
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