Enhanced perfusion following exposure to radiotherapy: A theoretical investigation.

Tumour angiogenesis leads to the formation of blood vessels that are structurally and spatially heterogeneous. Poor blood perfusion, in conjunction with increased hypoxia and oxygen heterogeneity, impairs a tumour's response to radiotherapy. The optimal strategy for enhancing tumour perfusion remains unclear, preventing its regular deployment in combination therapies. In this work, we first identify vascular architectural features that correlate with enhanced perfusion following radiotherapy, using in vivo imaging data from vascular tumours. Then, we present a novel computational model to determine the relationship between these architectural features and blood perfusion in silico. If perfusion is defined to be the proportion of vessels that support blood flow, we find that vascular networks with small mean diameters and large numbers of angiogenic sprouts show the largest increases in perfusion post-irradiation for both biological and synthetic tumours. We also identify cases where perfusion increases due to the pruning of hypoperfused vessels, rather than blood being rerouted. These results indicate the importance of considering network composition when determining the optimal irradiation strategy. In the future, we aim to use our findings to identify tumours that are good candidates for perfusion enhancement and to improve the efficacy of combination therapies.

E-cigarette vaping liquids and the flavoring chemical cinnamaldehyde perturb bone, cartilage and vascular development in zebrafish embryos.

As electronic cigarettes (e-cigarettes) become increasingly popular smoking devices, there is an increased risk for unintended exposure to e-cigarette liquids through improper disposal resulting in leaching into the environment, third hand vapor exposure through air, or embryonic exposure through maternal vaping. Thus, the safety of e-cigarettes for wildlife and developing embryos need to be thoroughly investigated. We examined perturbations in zebrafish embryonic development after exposures to two cinnamon flavored vaping liquids (with 12 mg/ml nicotine and without nicotine) for e-cigarettes from two different vendors, as well as the flavoring chemical cinnamaldehyde. We focused on the effects of the vaping liquids on hatching success and bone, cartilage and blood vessel development in 3-4 days old transgenic zebrafish larvae. We found that exposures to both of the vaping liquids perturbed the development of the cleithrum and craniofacial cartilage. Exposure to the liquids further caused non-overlapping and partially or completely missing intersegmental vessels. Hatching success was also reduced. Exposure to pure cinnamaldehyde replicated the effects of the vaping liquids with a 50% effect concentration (EC50) of 34-41 µM. Quantification of the amount of cinnamaldehyde in the vaping liquids by mass spectrometry revealed EC50s around 10-40 times lower than for pure cinnamaldehyde, suggesting that additional compounds or metabolites present in the vaping liquids mediate toxicity. Presence of nicotine in one of the vaping liquids decreased its EC50s about two fold compared to the liquid without nicotine. Exposure to the humectants propylene glycol and vegetable glycerin did not affect the vascular, cartilage or bone development in zebrafish embryos. In conclusion, our study shows that exposure to cinnamaldehyde containing vaping liquids causes severe tissue-specific defects in developing embryos.