Initialising ...
Initialising ...
Initialising ...
Initialising ...
Initialising ...
Initialising ...
Initialising ...
Yoshida, Yukari*; Mizohata, Kensuke*; Matsumura, Akihiko*; Isono, Mayu*; Yako, Tomoko*; Nakano, Takashi*; Funayama, Tomoo; Kobayashi, Yasuhiko; Kanai, Tatsuaki*
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 81, 2015/03
In the clinical application of carbon-ion (C-ion) radiation therapy in Japan, different RBE values of carbons have been used for clinical and biological endpoints. The biological RBE (bRBE) was estimated by a method that is based on the linear-quadratic (LQ) model, and was defined 
at the 10% surviving fraction of human salivary gland (HSG) tumor cells. However, many of biological parameters, that is, type of tissues, different sort of cells, oxygenation levels, and all, could affect radiosensitivity. Thus, normal human dermal fibroblasts (NHDF) cells were exposed to C-ion beams at Gunma University (10-80 keV/micrometer) and TIARA (108 and 158 keV/micrometer). The surviving fractions were analyzed with colony formation assays. The experimental RBE (eRBE) values were estimated from the radiation dose survival curve fitted by LQ model, and defined .
Saito, Katsuyo*; Funayama, Tomoo; Kobayashi, Yasuhiko; Murakami, Takashi*
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 83, 2015/03
Epigenetic modifiers, such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors, have emerged recently as promising anticancer agents and it has been expected that epigenetic modifiers may enhance the effect of other cancer therapeutics including radiotherapy. Therefore, we investigated whether the use of epigenetic modifiers could sensitize melanoma cells for the heavy-ion therapy. Murine B16F10 melanoma cells were treated with investigational or comparator epigenetic modifier, then exposed to carbon ions of JAEA-Takasaki. After irradiation, the viabilities of cells were evaluated by colony formation assay. Treatment of B16F10 melanoma cells with HDACi trichostatin A (TSA) in combination with heavy-ion radiation provided enhanced inhibition of colony formation. The data suggest that combination of an epigenetic modifier TSA together with heavy-ion therapy may provide improved therapeutic responses in melanoma patients.
Murata, Kazutoshi*; Noda, Shinei*; Oike, Takahiro*; Takahashi, Akihisa*; Yoshida, Yukari*; Suzuki, Yoshiyuki*; Ono, Tatsuya*; Funayama, Tomoo; Kobayashi, Yasuhiko; Takahashi, Takeo*; et al.
Journal of Radiation Research, 55(4), p.658 - 664, 2014/07
Times Cited Count：16 Percentile：55.86(Biology)The effect of carbon ion irradiation on cell motility through the Rho signaling pathway in the human lung adenocarcinoma cell line A549 was studied. At 48 h after irradiation, the cell motility of A549 cells became significantly greater, and the formation of protrusions significantly increased in cells irradiated with carbon ion. The observed increase in cell motility due to carbon ion irradiation was similar to that observed due to X-ray irradiation. Western-blot analysis showed that carbon ion irradiation increased P-MLC2-S19 expression compared with in unirradiated controls, while total MLC2 expression was unchanged. Exposure to a non-toxic concentration of Y-27632, a specific inhibitor of ROCK, reduced the expression of P-MLC2-S19 after C-ion irradiation, resulting in a significant reduction in migration. These data suggest that carbon irradiation increases cell motility in A549 cells via the Rho signaling pathway and that ROCK inhibition reduces that effect.
Moribayashi, Kengo
no journal, ,
Suzuki, Masao*; Funayama, Tomoo; Yokota, Yuichiro; Suzuki, Michiyo; Ikeda, Hiroko; Sakashita, Tetsuya; Kobayashi, Yasuhiko; Murakami, Takeshi*
no journal, ,
We irradiated either 4-cell lines with wild-type P53 or 4-cell lines with mutated-type P53 using the microbeams of JAEA-Takasaki collimated by 20
m in diameter. We can easily estimate the number of the directly irradiated cells to be just 0.04% of the total cells on the dish using the highly controlled microbeam irradiation system. The percent survival in the cells with wild-type P53 was around 90%, while almost 100% was observed in the cells with mutated-type P53. The results are consistent with the data using the carbon-ion broad beams with the shielding method at HIMAC. Our overall results showed that bystander cell-killing effect was observed in the cells with wild-type P53, but not in the P53-mutated cells. There is clear evidence that the spot scanning irradiation system of carbon ions enables the enhanced cell killing in cells with wild-type P53 gene via gap-junction mediated bystander effect.
Murata, Kazutoshi*; Noda, Shinei*; Oike, Takahiro*; Takahashi, Akihisa*; Yoshida, Yukari*; Suzuki, Yoshiyuki*; Ono, Tatsuya*; Funayama, Tomoo; Kobayashi, Yasuhiko; Takahashi, Takeo*; et al.
no journal, ,
This study aimed to investigate the effect of carbon ion (C-ion) irradiation on cell motility through the ras homolog gene family member (Rho) signaling pathway in the human lung adenocarcinoma cell line A549. Cell motility was assessed by a wound-healing assay, and the formation of cell protrusions was evaluated by F-actin staining. Cell viability was examined by the WST-1 assay. The expression of myosin light chain 2 (MLC2) and the phosphorylation of MLC2 at Ser19 (P MLC2-S19) were analyzed by Western blot. The data suggest that C-ion irradiation increases cell motility in A549 cells via the Rho signaling pathway and that ROCK inhibition reduces that effect.
Saito, Katsuyo*; Funayama, Tomoo; Kobayashi, Yasuhiko; Murakami, Takashi*
no journal, ,
Malignant melanoma is one of the most common cutaneous malignancies. Epigenetic modifiers, such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors, have emerged recently as promising anticancer agents and has been expected as a sensitizer for other cancer therapeutics including radiotherapy. In addition, the biological effects of the high linear energy transfer (LET) heavy-ion radiation are more pronounced than the low-LET radiation. These accumulating evidences allowed us to investigate whether the use of HDACi could sensitize melanoma cells for the heavy-ion therapy. Treatment of B16F10 melanoma cells with HDACi in combination with heavy-ion radiation provided enhanced anti-tumor effects. These data suggest that combination of HDACi together with heavy-ion therapy may provide improved therapeutic responses in melanoma patients.
