Radiotherapy is an essential step during the treatment of glioblastoma multiforme (GBM), one of the most lethal malignancies. The survival in patients with GBM was improved by the current standard of care for GBM established in 2005 but has stagnated since then. Since GBM is a radioresistant malignancy and the most of GBM recurrences occur in the radiotherapy field, increasing the effectiveness of radiotherapy using high-Z metal nanoparticles (NPs) has recently attracted attention. This review summarizes the progress in radiotherapy approaches for the current treatment of GBM, the physical and biological mechanisms of radiosensitization through high-Z metal NPs, and the results of studies on radiosensitization in the in vitro and in vivo GBM models using high-Z metal NPs to date.

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Oxidative stress plays an important role in the progression of various neuronal diseases including ischemia. Heat shock protein 22 (HSP22) is known to protect cells against oxidative stress. However, the protective effects and mechanisms of HSP22 in hippocampal neuronal cells under oxidative stress remain unknown. In this study, we determined whether HSP22 protects against hydrogen peroxide (H2O2)-induced oxidative stress in HT-22 using Tat-HSP22 fusion protein. We found that Tat-HSP22 transduced into HT-22 cells and that H2O2-induced cell death, oxidative stress, and DNA damage were significantly reduced by Tat-HSP22. In addition, Tat-HSP22 markedly inhibited H2O2-induced mitochondrial membrane potential, cytochrome c release, cleaved caspase-3, and Bax expression levels, while Bcl-2 expression levels were increased in HT-22 cells. Further, we showed that Tat-HSP22 transduced into animal brain and inhibited cleaved-caspase-3 expression levels as well as significantly inhibited hippocampal neuronal cell death in the CA1 region of animals in the ischemic animal model. In the present study, we demonstrated that transduced Tat-HSP22 attenuates oxidative stress-induced hippocampal neuronal cell death through the mitochondrial signaling pathway and plays a crucial role in inhibiting neuronal cell death, suggesting that Tat-HSP22 protein may be used to prevent oxidative stress-related brain diseases including ischemia.

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In the present study, we searched for possible candidates that can prevent ischemic damage in the rabbit spinal cord. For this study, we used two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, in sham- and ischemia-operated animals. As the level of protein disulfide-isomerase A3 (PDIA3) significantly decreased 3 h after ischemia/reperfusion, we further investigated its possible role against ischemic damage using an in vitro spinal cord cell line and in vivo spinal cord ischemic model. The administration of Tat-PDIA3 significantly reduced the hydrogen peroxide-induced formation of reactive oxygen species and cell death, based on terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling and a colorimetric WST-1 assay. Further, Tat-PDIA3 significantly ameliorated the ischemia-induced deficits in motor function, based on Tarlov’s criteria, 24–72 h after ischemia/reperfusion, as well as the degeneration of motor neurons in the ventral horn 72 h after ischemia/reperfusion. Tat-PDIA3 administration also reduced the ischemia-induced activation of microglia and lipid peroxidation in the motor neurons 72 h after ischemia/reperfusion. PDIA3 also potentially ameliorated the ischemia-induced increase in oxidative markers in serum and decreased the activity of Cu,Zn-superoxide dismutase, Mn-superoxide dismutase, and glutathione peroxidase in spinal cord homogenates, 24 h and 72 h after ischemia/reperfusion. These results suggest that Tat-PDIA3 could be used to protect spinal cord neurons from ischemic damage, due to its modulatory action on the oxidative/anti-oxidative balance. Tat-PDIA3 could be applicable to protects neurons from the ischemic damage induced by thoracoabdominal aorta obstruction.

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