High frequency of MYC gene amplification is a common feature of radiation‐induced sarcomas. Further results from EORTC STBSG TL 01/01

Irradiation is a major causative factor among the small subgroup of sarcomas with a known etiology. The prognosis of radiation‐induced sarcomas (RIS) is significantly worse than that of their spontaneous counterparts. The most frequent histological subtypes include undifferentiated pleomorphic sarcomas, angiosarcomas, and leiomyosarcomas. A high frequency of MYC amplifications in radiation‐induced angiosarcomas, but not in primary angiosarcomas, has recently been described. To investigate whether MYC amplifications are also frequent in RIS other than angiosarcomas, we analyzed the MYC amplification status of 83 RIS and 192 sporadic sarcomas by fluorescence in situ hybridization. We found significantly higher numbers of MYC amplifications in RIS than in sporadic sarcomas (P < 0.0001), especially in angiosarcomas, undifferentiated pleomorphic sarcomas, and leiomyosarcomas. Angiosarcomas were special in that MYC amplifications were particularly frequent and always high level, while other RIS showed low‐level amplifications. We conclude that MYC amplifications are a frequent feature of RIS as a group and may contribute to the biology of these tumors. © 2012 Wiley Periodicals, Inc.     

Three‐dimensional imaging and analysis of human cartilage degeneration using Optical Coherence Tomography

Optical Coherence Tomography (OCT) is an evolving imaging technology allowing non‐destructive imaging of cartilage tissue at near‐histological resolution. This study investigated the diagnostic value of real time 3‐D OCT in comparison to conventional 2‐D OCT in the comprehensive grading of human cartilage degeneration. Fifty‐three human osteochondral samples were obtained from eight total knee arthroplasties. OCT imaging was performed by either obtaining a single two‐dimensional cross‐sectional image (2‐D OCT) or by collecting 100 consecutive parallel 2‐D OCT images to generate a volumetric data set of 8 × 8 mm (3‐D OCT). OCT images were assessed qualitatively according to a modified version of the DJD classification and quantitatively by algorithm‐based evaluation of surface irregularity, tissue homogeneity, and signal attenuation. Samples were graded according to the Outerbridge classification and statistically analyzed by one‐way ANOVA, Kruskal Wallis and Tukey's or Dunn's post‐hoc tests. Overall, the generation of 3‐D volumetric datasets and their multiple reconstructions such as rendering, surface topography, parametric, and cross‐sectional views proved to be of potential diagnostic value. With increasing distance to the mid‐sagittal plane and increasing degeneration, score deviations increased, too. In conclusion, 3‐D imaging of cartilage with image analysis algorithms adds considerable potential diagnostic value to conventional OCT diagnostics. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:651–659, 2015.     

Combined Computational and Experimental Approach to Improve the Assessment of Mitral Regurgitation by Echocardiography

Mitral regurgitation (MR) is one of the most frequent valvular heart diseases. To assess MR severity, color Doppler imaging (CDI) is the clinical standard. However, inadequate reliability, poor reproducibility and heavy user-dependence are known limitations. A novel approach combining computational and experimental methods is currently under development aiming to improve the quantification. A flow chamber for a circulatory flow loop was developed. Three different orifices were used to mimic variations of MR. The flow field was recorded simultaneously by a 2D Doppler ultrasound transducer and Particle Image Velocimetry (PIV). Computational Fluid Dynamics (CFD) simulations were conducted using the same geometry and boundary conditions. The resulting computed velocity field was used to simulate synthetic Doppler signals. Comparison between PIV and CFD shows a high level of agreement. The simulated CDI exhibits the same characteristics as the recorded color Doppler images. The feasibility of the proposed combination of experimental and computational methods for the investigation of MR is shown and the numerical methods are successfully validated against the experiments. Furthermore, it is discussed how the approach can be used in the long run as a platform to improve the assessment of MR quantification.     

The influence of structural gradients in large pore organosilica materials on the capabilities for hosting cellular communities

Cells exist in the so-called extracellular matrix (ECM) in their native state, and numerous future applications require reliable and potent ECM-mimics. A perspective, which goes beyond ECM emulation, is the design of a host-material with features which are not accessible in the biological portfolio. Such a feature would, for instance, be the creation of a structural or chemical gradient, and to explore how this special property influences the biological processes. First, we wanted to test if macroporous organosilica materials with appropriate surface modification can act as a host for the implementation of human cells like HeLa or LUHMES. It was possible to use a commercially available polymeric foam as a scaffold and coat it with a thiophenol-containing organosilica layer, followed by biofunctionalization with biotin using click chemistry and the subsequent coupling of streptavidin–fibronectin to it. More importantly, deformation of the scaffold allowed the generation of a permanent structural gradient. In this work, we show that the structural gradient has a tremendous influence on the capability of the described material for the accommodation of living cells. The introduction of a bi-directional gradient enabled the establishment of a cellular community comprising different cell types in spatially distinct regions of the material. An interesting perspective is to study communication between cell types or to create cellular communities, which can never exist in a natural environment.

Chemical and structural gradients in biofunctionalized organosilica–polymer nanocomposites control cell adhesion properties and open perspectives for artificial cellular community systems.