玉利 勇樹

Vascular endothelial growth factor (VEGF) is closely related to angiogenesis. Anticancer therapy by inhibiting VEGF signaling is well established. However, the role of VEGF in cell–cell communication during the response to ionizing radiation is not well understood. Here, we examined the role of VEGF on radiosensitivity of cells. The addition of recombinant VEGF (rVEGF) on cultured rat C6 glioma cells showed a radioprotective effects on X-ray irradiation and reduced oxidative stress. These effects were also observed by endogenous VEGF in supernatant of C6 glioma cells. Reduction of oxidative stress by VEGF is suggested to underlie the radioprotective effects. The mechanism of VEGF-induced reduction of oxidative stress was indicated by a decreased oxygen consumption rate (OCR) in mitochondria. However, the number of DNA double-strand breaks (DSB) immediately after irradiation was not reduced by the treatment with VEGF. These results suggest that VEGF plays a role in cell survival after irradiation by controlling the oxidative condition through mitochondrial function that is independent of the efficiency of DSB induction.

Radiation-induced liver diseases, including liver fibrosis, occurs when radiation damages the liver. Basic research on hepatic fibrosis, which is a late radiation injury, is necessary for evaluating adverse liver events occurring after boron neutron capture therapy. This study was conducted to establish a method for analyzing the negative effect such as fibrosis in the liver tissue after boron neutron capture therapy. Female C57BL6 mice were injected with p-boronophenylalanine solution subcutaneously at 2 h before neutron irradiation. Masson trichrome staining was performed to determine the degree of liver fibrosis. The degree of fat accumulation in mouse normal liver tissue after boron neutron capture therapy was evaluated using hematoxylin and eosin staining and triglyceride quantification. Western blotting was performed to determine the expression level of Sonic Hedgehog. Liver fat accumulation and fibrosis were significantly increased in the neutron irradiation group injected with p-boronophenylalanine compared with control group. In addition, Sonic Hedgehog expression was increased in response to boron neutron capture therapy-induced liver injury and was involved in liver fibrosis. Hepatocellular fat accumulation and Hedgehog signaling activation may be indicators of adverse events related to boron neutron capture therapy associated with liver fibrosis.

<title>Abstract</title> The aim of this study is the development of an irradiation method for the treatment of superficial tumours using a hydrogel bolus to produce thermal neutrons in accelerator-based Boron Neutron Capture Therapy (BNCT). To evaluate the neutron moderating ability of a hydrogel bolus, a water phantom with a hydrogel bolus was irradiated with an epithermal neutron beam from a cyclotron-based epithermal neutron source. Phantom simulating irradiation to the plantar position was manufactured using three-dimensional printing technology to perform an irradiation test of a hydrogel bolus. Thermal neutron fluxes on the surface of a phantom were evaluated and the results were compared with the Monte Carlo-based Simulation Environment for Radiotherapy Applications (SERA) treatment planning software. It was confirmed that a hydrogel bolus had the same neutron moderating ability as water, and the calculation results from SERA aligned with the measured values within approximately 5%. Furthermore, it was confirmed that the thermal neutron flux decreased at the edge of the irradiation field. It was possible to uniformly irradiate thermal neutrons by increasing the bolus thickness at the edge of the irradiation field, thereby successfully determining uniform dose distribution. An irradiation method for superficial tumours using a hydrogel bolus in the accelerator-based BNCT was established.

BACKGROUND: Peroxiredoxin 1 (PRDX1) is a member of a ubiquitous family of thiol peroxidases that catalyze the reduction of peroxides, including hydrogen peroxide. It functions as an antioxidant enzyme, similar to catalase and glutathione peroxidase. PRDX1 was recently shown act as a sensor of reactive oxygen species (ROS) and play a role in ROS-dependent intracellular signaling pathways. To investigate its physiological functions, PRDX1 was conditionally disrupted in chicken DT40 cells in the present study. RESULTS: The depletion of PRDX1 resulted in cell death with increased levels of intracellular ROS. PRDX1-depleted cells did not show the accumulation of chromosomal breaks or sister chromatid exchange (SCE). These results suggest that cell death in PRDX1-depleted cells was not due to DNA damage. 2-Mercaptoethanol protected against cell death in PRDX1-depleted cells and also suppressed elevations in ROS. CONCLUSIONS: PRDX1 is essential in chicken DT40 cells and plays an important role in maintaining intracellular ROS homeostasis (or in the fine-tuning of cellular ROS levels). Cells deficient in PRDX1 may be used as an endogenously deregulated ROS model to elucidate the physiological roles of ROS in maintaining proper cell growth.

Synovial sarcoma is a rare tumor requiring new treatment methods. A 46-year-old woman with primary monophasic synovial sarcoma in the left thigh involving the sciatic nerve, declining surgery because of potential dysfunction of the affected limbs, received two courses of BNCT. The tumor thus reduced was completely resected with no subsequent recurrence. The patient is now able to walk unassisted, and no local recurrence has been observed, demonstrating the applicability of BNCT as adjuvant therapy for synovial sarcoma. Further study and analysis with more experience accumulation are needed to confirm the real impact of BNCT efficacy for its application to synovial sarcoma.