Micro-Vessels-Like 3D Scaffolds for Studying the Proton Radiobiology of Glioblastoma-Endothelial Cells Co-Culture Models.

Glioblastoma (GBM) is a devastating cancer of the brain with an extremely poor prognosis. While X-ray radiotherapy and chemotherapy remain the current standard, proton beam therapy is an appealing alternative as protons can damage cancer cells while sparing the surrounding healthy tissue. However, the effects of protons on in vitro GBM models at the cellular level, especially when co-cultured with endothelial cells, the building blocks of brain micro-vessels, are still unexplored. In this work, novel 3D-engineered scaffolds inspired by the geometry of brain microvasculature are designed, where GBM cells cluster and proliferate. The architectures are fabricated by two-photon polymerization (2PP), pre-cultured with endothelial cells (HUVECs), and then cultured with a human GBM cell line (U251). The micro-vessel structures enable GBM in vivo-like morphologies, and the results show a higher DNA double-strand breakage in GBM monoculture samples when compared to the U251/HUVECs co-culture, with cells in 2D featuring a larger number of DNA damage foci when compared to cells in 3D. The discrepancy in terms of proton radiation response indicates a difference in the radioresistance of the GBM cells mediated by the presence of HUVECs and the possible induction of stemness features that contribute to radioresistance and improved DNA repair.

Tissue synchronisation imaging accurately measures left ventricular dyssynchrony and predicts response to cardiac resynchronisation therapy.

BACKGROUND: Tissue synchronisation imaging (TSI) is a new technique to assess left ventricular (LV) dyssynchrony. OBJECTIVES: The value of using TSI to automatically assess LV dyssynchrony compared with manual assessment of LV dyssynchrony from colour-coded tissue Doppler imaging (TDI), and to evaluate the value of TSI to predict response to cardiac resynchronisation therapy (CRT). METHODS: 60 symptomatic patients with heart failure with depressed LV ejection fraction (LVEF) and QRS >120 ms were evaluated clinically and echocardiographically at baseline and after 6 months of CRT. LV dyssynchrony was measured manually using velocity tracings from the colour-coded TDI and automatically using TSI. LV volumes and LVEF were assessed from two-dimensional echocardiography. Clinical responders had to exhibit an improvement in New York Heart Association functional class by > or =1 score and an improvement by > or =25% in 6 min walking distance after 6 months. Reverse LV remodelling was defined as a reduction of > or =15% LV end-systolic volume. RESULTS: An excellent correlation was observed between LV dyssynchrony measured manually and automatically derived by TSI (r = 0.95, p<0.001). 34 patients showed clinical response after 6 months of CRT and 32 patients showed reverse remodelling. Baseline characteristics were comparable between responders and non-responders, except for more extensive LV dyssynchrony in the responders: 78 (26) vs 29 (29) ms (p<0.001) as assessed manually, and 79 (29) vs 28 (27) ms (p<0.001) as assessed with TSI. Using a cut-off value of 65 ms to define extensive LV dyssynchrony, TSI had a sensitivity of 81% with a specificity of 89% to predict reverse LV remodelling. CONCLUSION: TSI allows automatic and reliable assessment of LV dyssynchrony and predicts reverse LV remodelling after CRT.