@article{oai:repo.qst.go.jp:00049574,
 author = {Ho Kim, Eun and Mi-Sook, Kim and Kyung-Hee, Lee and Sai, Sei and Kyoung Jeong, Youn and Jae-Soo, Koh and Chang-Bae, Kong and Ho Kim, Eun and Sai, Sei},
 issue = {4},
 journal = {International journal of oncology},
 month = {Oct},
 note = {Osteosarcoma (OS) is a malignant tumor of the bone derived from primitive transformed cells of the mesenchymal origin. Local low-linear energy transfer (LET) radiotherapy has limited benefits on OS owing to its radioresistance. Thus, this study aimed to investigate the effects of high-LET radiation on human OS. Therefore, the human OS cell lines, U2O2 and KHOS/NP, were examined in vitro, or an orthotopic mouse xenograft model was studied in vivo after treatment with low-LET (gamma-ray) and high-LET (neutron) radiation. Notably, OS cells were significantly more sensitive to high-LET radiation in vitro and in the orthotopic xenograft tumor model. Specifically, neutron radiation treatment increased the relative percentage of apoptotic sub-G1 phase cells via caspase-3/9 activation; increased intracellular reactive oxygen species, autophagy, and DNA damage; and decreased invasion and migration. Similarly, the mean size of gamma-irradiated (8 Gy) orthotopic KHOS/NP OS was 195 mm3 at 6 weeks after gamma-irradiation (8 Gy), but it was only 150 mm3 in mice treated with high-LET neutron radiotherapy. Significantly, our results provide a rationale for the use of high-LET radiotherapy to treat patients with OS.},
 pages = {1124--1134},
 title = {Effect of low- and high-linear energy transfer radiation on in vitro and orthotopic in vivo models of osteosarcoma by activation of caspase-3 and -9.},
 volume = {51},
 year = {2017}
}