ONO Koji Kyoto University, research Reactor Institute, Professor (90122407)
MIYATAKE Shinichi Osaka Medical College, Faculty of Medicine, Associate Professor (90209916)
KASAOKA Satoshi Hiroshima International University, Faculty of Pharmaceutical Sciences, Laboratory of Pharmaceutics, Assistant Professor (90338690)
ARIYOSHI Yasunori Osaka Medical College, Faculty of Medicine, Junior Associate Professor (70330066)
KIMURA Yoshihiro Osaka Medical College, Faculty of Medicine, Assistant Professor (00351388)
|Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
For the clinical study, the therapeutic effects of BNCT were evaluated on the basis of diagnostic imaging, as well as 18-BPA PET and clinical findings. MRI results revealed a reduction in signal intensity in T2-weighted images, while a reduction in the signal enhancing effect in the contrast images was observed in addition to tumor shrinkage. In a BNCT examination, oral mucositis, slight malaise, and hair loss were noted, however, there were no serious side effects following treatment, demonstrating a favorable therapeutic effect.
For the basic study, transferrin receptor expression was examined using the oral squamous cell carcinoma cell lines SAS and OSC-19, and the results showed expression of the receptor on the surface of SAS cells. Further, to improve 10B uptake by the cells, we made preparations of BSH embedded in liposome (liposome-BSH), BSH embedded in liposome and modified with polyethylene glycol (PEG-liposome-BSH), and PEG-liposome-BSH bound with transferrin (TF-PEG-liposome-BSH), then examined the differences in uptake by the cancer cells. Cellular uptake was significantly increased with TF-PEG-liposome as compared to the other compounds. As for the maintenance of intracellular concentration, it was also demonstrated that TF-PEG-liposome-BSH remained longer than the others after the removal of the boron compound. In contrast, excessive TF inhibited the uptake of TF-PEG-liposome-BSH by SAS cells. In an experiment using tumor bearing mice, it was confirmed that 10B uptake to the tumors was increased with that compound.
Our findings demonstrated that TF, which is excessively expressed in tumor cells, has beneficial effects to increase the amount of 10B uptake by tumor cells and maintain its concentration, suggesting that TF may be useful as a carrier in future clinical practice.