A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance

Glioblastoma is among the most lethal cancers, with no known cure. A multitude of therapeutics are being developed or in clinical trials, but currently there are no ways to predict which patient may benefit the most from which drug. Assays that allow prediction of the tumor’s response to anti-cancer drugs may improve clinical decision-making. Here, we present a high-density 3D primary cell culture model for short-term testing from resected glioblastoma tissue that is set up on the day of surgery, established within 7 days and viable for at least 3 weeks. High-density 3D cultures contain tumor and host cells, including microglia, and retain key histopathological characteristics of their parent tumors, including proliferative activity, expression of the marker GFAP, and presence of giant cells. This provides a proof-of-concept that 3D primary cultures may be useful to model tumor heterogeneity. Importantly, we show that high-density 3D cultures can be used to test chemotherapy response within a 2–3-week timeframe and are predictive of patient response to Temozolomide therapy. Thus, primary high-density 3D cultures could be a useful tool for brain cancer research and prediction of therapeutic resistance

Diffusion of Zn in nanostructured aluminum alloys produced by surface mechanical attrition treatment

After surface nanocrystallization of pure Al and a cast Al-Si alloy through surface mechanical attrition treatment (SMAT), 200- to 300-lm-thick Zn coatings were deposited on the nanostructured surface using the clod spray technique. Subsequently, diffusion of Zn into the Al substrate was induced by postspray annealing treatment at various temperatures for different times. The diffusion kinetics of Zn in the nanostructured surface layers was studied in terms of the Zn concentration profile in the substrate by using scanning electron microscopy (SEM) and electron probe microscopy analysis (EPMA). Experimental results show that not only the diffusivity of Zn in the nanocrystalline grains is significantly increased compared with the diffusion in the coarse grained counterpart, but the temperature at which noticeable Zn diffusion in Al alloys occurs is also reduced from 573 K (300 °C) in coarse-grained Al alloys to 523 K (250 °C) in nanostructured alloys. In addition, because the nanocrystalline grains produced by SMAT in Al-Si alloys are much smaller than those in pure Al due to the effect of eutectic Si, the diffusion of Zn in the SMATed Al-Si alloy is much faster than that in the SMATed pure Al. It is believed that the high diffusivity of Zn in the nanocrystalline Al grains is attributed to the large fraction of grain boundaries that act as fast diffusion channel. The effect of thermal stability of the nanocrystalline grains on Zn diffusion in the SMATed Al alloys is also discussed