Pro-apoptotic Noxa is involved in ablative focal irradiation-induced lung injury

Although lung injury including fibrosis is a well-documented side effect of lung irradiation, the mechanisms underlying its pathology are poorly understood. X-rays are known to cause apoptosis in the alveolar epithelial cells of irradiated lungs, which results in fibrosis due to the proliferation and differentiation of fibroblasts and the deposition of collagen. Apoptosis and BH3-only pro-apoptotic proteins have been implicated in the pathogenesis of pulmonary fibrosis. Recently, we have established a clinically analogous experimental model that reflects focal high-dose irradiation of the ipsilateral lung. The goal of this study was to elucidate the mechanism underlying radiation-induced lung injury based on this model. A radiation dose of 90 Gy was focally delivered to the left lung of C57BL/6 mice for 14 days. About 9 days after irradiation, the mice began to show increased levels of the pro-apoptotic protein Noxa in the irradiated lung alongside increased apoptosis and fibrosis. Suppression of Noxa expression by small interfering RNA protected cells from radiation-induced cell death and decreased expression of fibrogenic markers. Furthermore, we showed that reactive oxygen species participate in Noxa-mediated, radiation-induced cell death. Taken together, our results show that Noxa is involved in X-ray-induced lung injury.ope

Feasibility Study of a Custom-made Film for End-to-End Quality Assurance Test of Robotic Intensity Modulated Radiation Therapy System

This paper aims to verify the clinical feasibility of a custom-made film created by a laser cutting tool for End-to-End (E2E) quality assurance in robotic intensity modulated radiation therapy system. The custom-made film was fabricated from the Gafchromic EBT3 film with the size of 8"×10" using a drawing that is identical to the shape and scale of the original E2E film. The drawing was created by using a computer aided design program with the image file, which is obtained by scanning original E2E film. Beam delivery and evaluations were respectively performed with the original film and the custom-made film using fixed-cone collimator on three tracking modes: 6D skull (6DS), Xsight spine (XS), and Xsight lung (XL). The differences between total targeting errors of the original and custom-made films were recorded as 0.17 mm, 0.3 mm, and 0.17 mm at 6DS, XS, and XL tracking modes, respectively. This indicates that the custom-made film could yield nearly equivalent results to those of the original E2E film, given the uncertainties caused by distortions during film scanning and vibrations associated with film cutting. By confirming the clinical feasibility of a custom-made film for E2E testing, it can be expected that economic efficiency of the testing will increase accordingly.ope