Figure 5.

Effects of radiation-associated metabolic alteration on GBM outcome: (A) Survival curves: Graphs show difference between survival of irradiated (IR) mice cohorts injected with GBM143 24 hrs post-irradiation (short-term IR, ST-IR) or 2 months post-irradiation (long-term IR, LT-IR). Statistical significance is represented as ^**p < 0.01, ^****p < 0.0001. (B) Proposed model for radiation associated metabolic alterations and their effects on cell processes and glioblastoma multiforme (GBM) outcome. The box marked with yellow outline (irradiated by RT) shows metabolic changes in the radiated brain stromal microenvironment, with rise in energy carriers ATP and GTP, and reduction in levels of antioxidants, ascorbate and glutathione, and the cellular processes affected by them. With IR, continued and excess rise in levels of energy carriers and expense of antioxidants within stromal cells of the brain can lead to altered extracellular milieu. Pathophysiological changes in the extracellular milieu, which can be immediate or long term caused by the radiation are enlisted in purple box. These alterations would collectively contribute to radiated stroma and GBM cell interactions that are permissive to GBM growth and, aggressive recurrence. Translational relevance of the study and its insights gained from pre-radiated brain microenvironment to prevent secondary and recurrent GBM spread is illustrated in Figure S5.