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.

Rectum dose analysis employing a multi-purpose brachytherapy phantom.

PURPOSE: It is difficult to reproduce a brachytherapy measurement because of changes in the rectal shape during inter-fraction. We constructed a multi-purpose brachytherapy phantom (MPBP) and reproduced the same conditions found in actual therapy. We further attempted to apply the measured optimal dose to reduce rectal complications. METHODS: A measured dose was administered at rectal reference point R1 using a diode detector in four patients who used a tandem and ovoid in brachytherapy for carcinoma of the cervix. A total number of 20 rectal dose measurements were performed five times per patient. In addition, discrepancies in the set-up of the diode detector were analyzed with each repetitive measurement. After reproducing the same conditions as found in actual therapy using a multi-function applicator (MFA) in the multi-purpose brachytherapy phantom constructed for this study, the dose was measured at reference points in the rectum using a thermoluminescence dosimeter (TLD). RESULTS: According to the discrepancies measured in the set-up using a diode detector, Patient 1 showed a maximum value of 11.25 +/- 0.95 mm in the Y direction, Patients 2 and 3 exhibited 9.90 +/- 2.40 mm and 20.85 +/- 4.50 mm in the Z direction, respectively. Patient 4 showed 19.15 +/- 3.33 mm in the Z direction. In addition, values of the mean dose according to the position of the diode detector were recorded as 122.82 +/- 7.96-323.78 +/- 11.16 cGy. In the measured results for TLD in an MPBP, relative error for Patients 1 and 4 at the rectal reference point R2 were a maximum of 8.6 and 7.7%, respectively. For Patients 2 and 3 they were 1.7 and 1.2%, respectively. Furthermore, the dose measured at point R1 and R2 exhibited values approximately 1.7-8.6% higher than the dose calculated in advance, excluding point R1 in Patient 2. The discrepancies in the set-up owing to repetitive measurements and alterations in dosage according to these changes were not analyzed. It was evident that the relative error between the calculated and measured value was within 15%, which was allowable according to the recommendations by the American Association of Physicists in Medicine (AAPM). CONCLUSIONS: The multi-purpose brachytherapy phantom constructed for this study successfully reproduced an optimal dose measured under the same conditions found in actual therapy in which the dose was precisely analyzed at a rectal reference point. In addition, these results were considered reliable and applicable for dose optimization before applying therapy using the measured data from the phantom in order to reduce rectal complications.