Bleomycin (BLM) is an anti-cancer drug that can induce formation of reactive oxygen species (ROS). To investigate the association between up-regulation of antioxidant enzymes and coenzyme Q(10) (CoQ(10)) in acquired BLM resistance, one BLM-resistant clone, SBLM24 clone, was selected from a human oral cancer cell line, SCC61 clone. The BLM resistance of SBLM24 clone relative to a sub-clone of SCC61b cells was confirmed by analysis of clonogenic ability and cell cycle arrest. CoQ(10) levels and levels of Mn superoxide dismutase, glutathione peroxidase 1, catalase and thioredoxin reductase 1 were augmented in SBLM24 clone although there was also a mild increase in the expression of BLM hydrolase. Suppression of CoQ(10) levels by 4-aminobenzoate sensitized BLM-induced cytotoxicity. The results of suppression on enhanced ROS production by BLM and the cross-resistance to hydrogen peroxide in SBLM24 clone further demonstrated the development of adaptation to oxidative stress during the formation of acquired BLM resistance.
Purpose: Breast immobilization with personalized breast holder (PERSBRA) is a promising approach for normal organ protection during whole breast radiotherapy. The aim of this study is to evaluate the skin surface dose for breast radiotherapy with PERSBRA using different radiotherapy techniques. Materials and methods: We designed PERSBRA with three different mesh sizes (large, fine and solid) and applied them on an anthropomorphic(Rando) phantom. Treatment planning was generated using hybrid, intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques to deliver a prescribed dose of 5000 cGy in 25 fractions accordingly. Dose measurement with EBT3 film and TLD were taken on Rando phantom without PERSBRA, large mesh, fine mesh and solid PERSBRA for (a) tumor doses, (b) surface doses for medial field and lateral field irradiation undergoing hybrid, IMRT, VMAT techniques. Results: The tumor dose deviation was less than five percent between the measured doses of the EBT3 film and the TLD among the different techniques. The application of a PERSBRA was associated with a higher dose of the skin surface. A large mesh size of PERSBRA was associated with a lower surface dose. The findings were consistent among hybrid, IMRT, or VMAT techniques. Conclusions: Breast immobilization with PERSBRA can reduce heart toxicity but leads to a build-up of skin surface doses, which can be improved with a larger mesh design for common radiotherapy techniques.
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