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Journal Articles

Oxygen enhancement ratios of cancer cells after exposure to intensity modulated X-ray fields; DNA damage and cell survival

Matsuya, Yusuke; McMahon, S. J.*; Butterworth, K. T.*; Naijo, Shingo*; Nara, Isshi*; Yachi, Yoshie*; Saga, Ryo*; Ishikawa, Masayori*; Sato, Tatsuhiko; Date, Hiroyuki*; et al.

Physics in Medicine & Biology, 66(7), p.075014_1 - 075014_11, 2021/04

 Times Cited Count:0 Percentile:0.01(Engineering, Biomedical)

Hypoxic cancer cells within solid tumours show radio-resistance, leading to malignant progression in fractionated radiotherapy. When prescribing dose to tumours under heterogeneous oxygen pressure with intensity-modulated radiation fields, intercellular signalling could have an impact on radiosensitivity between in-field and out-of-field cells. However, the impact of hypoxia on radio-sensitivity under modulated radiation intensity remains uncertain. In this study, we investigate the impact of hypoxia on in-field and out-of-field radio-sensitivities using two types of cancer cells. These in vitro measurements indicate that hypoxia apparently impacts out-of-field cells, although the OER values in out-of-field cells were smaller compared to those for in-field and uniformly irradiated cells. These decreased radio-sensitivities of out-of-field cells were shown as a consistent tendency for both DSB and cell death endpoints, suggesting that radiation-induced intercellular communication is of importance in treatment planning with intensity-modulated radiotherapy.

Journal Articles

4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication

Saga, Ryo*; Matsuya, Yusuke; Takahashi, Rei*; Hasegawa, Kazuki*; Date, Hiroyuki*; Hosokawa, Yoichiro*

Scientific Reports (Internet), 11(1), p.8258_1 - 8258_10, 2021/04

 Times Cited Count:0 Percentile:0(Multidisciplinary Sciences)

Hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which indicates the involvement of intercellular communication. In addition, the oxidative stress level, which leads to DNA damage induction, significantly increased under 4-MU treatment, and the radiosensitization by 4-MU can be suppressed by the inhibitors for intercellular communication. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.

Journal Articles

A Model for estimating dose-rate effects on cell-killing of human melanoma after boron neutron capture therapy

Matsuya, Yusuke; Fukunaga, Hisanori*; Omura, Motoko*; Date, Hiroyuki*

Cells, 9(5), p.1117_1 - 1117_16, 2020/05

 Times Cited Count:5 Percentile:67.45(Cell Biology)

When delivering a high absorbed dose to cancer cells following boron neutron capture therapy (BNCT), heterogeneous dose distribution, the time line of $$^{10}$$B concentrations and the long dose-delivery time must be considered. Changes in radiosensitivity during such a long dose-delivery time can reduce the probability of tumor control; however, such change has not yet been evaluated. Here, we developed a cell-killing model that accounts for changes in microdosimetric quantities and dose rates depending on the $$^{10}$$B concentration and investigated dose-rate effects (cell recovery during BNCT irradiation) of melanoma. The developed model shows good agreement with in-vitro experimental survival data for exposure to $$^{60}$$Co $$gamma$$-rays, thermal neutrons, and BNCT. The model estimation suggests that the impact of cell recovery during BNCT irradiations with high linear energy transfer (LET) is reduced compared to $$^{60}$$Co $$gamma$$-rays irradiation with low LET. The present model is expected to predict radio-sensitivity for BNCT irradiations.

Journal Articles

A Theoretical cell-killing model to evaluate oxygen enhancement ratios at DNA damage and cell survival endpoints in radiation therapy

Matsuya, Yusuke; Sato, Tatsuhiko; Nakamura, Rui*; Naijo, Shingo*; Date, Hiroyuki*

Physics in Medicine & Biology, 65(9), p.095006_1 - 095006_12, 2020/05

 Times Cited Count:1 Percentile:33.12(Engineering, Biomedical)

Radio-resistance induced under low oxygen pressure plays an important role in malignant progression in fractionated radiotherapy. For the general approach to predict cell killing under hypoxia, cell-killing models (e.g., the Linear-Quadratic model) have to be fitted to ${it in vitro}$ experimental survival data for both normoxia and hypoxia to obtain the oxygen enhancement ratio (OER). However, model parameters for every oxygen condition needs to be considered by model-fitting approaches. This is inefficient for fractionated irradiation planning. Here, we present an efficient model for fractionated radiotherapy the integrated microdosimetric-kinetic model including cell-cycle distribution and the OER at DNA double-strand break endpoint. The cell survival curves described by this model can reproduce the ${it in vitro}$ experimental survival data for both acute and chronic low oxygen concentrations. The OER$$_{DSB}$$ used for calculating cell survival agrees well with experimental DSB ratio of normoxia to hypoxia. This work provides biological effective dose (BED) under various oxygen conditions including its uncertainty, which can contribute to creating fractionated regimens for multi-fractionated radiotherapy. If the oxygen concentration in a tumor can be quantified by medical imaging, the present model will make it possible to estimate the cell-killing and BED under hypoxia in more realistic intravital situations.

Journal Articles

Track structure study for energy dependency of electrons and X-rays on DNA double-strand break induction

Yachi, Yoshie*; Yoshii, Yuji*; Matsuya, Yusuke; Mori, Ryosuke*; Oikawa, Joma*; Date, Hiroyuki*

Scientific Reports (Internet), 9(1), p.17649_1 - 17649_8, 2019/11

 Times Cited Count:1 Percentile:15.41(Multidisciplinary Sciences)

Radiation weighting factor for photon and electron is defined as 1.0 independently these energies. However, it should be noted that the biological effects after 29 kVp X-rays is relative higher than standard 200 kVp X-rays at the endpoint of ${it in vitro}$. And it is of importance to evaluate electrons generated via interaction of photons with matter. Here, we evaluated the energy concentration along electron track (dose-mean lineal energy) on chromosome (micron-meter) scales by Monte Carlo simulation, and measured the DNA double-strand breaks (DSBs) induction. From the cell experiments, the DSBs induction after diagnostic X-rays exposure (60-100 kVp) is higher than those with therapeutic X-rays (6 MV). In the relation between the dose-mean lineal energy and the number of DSBs, it was shown that lower energy photons might induce more biological impact due to the interaction by low energy electron. This study implies that radiation weighting factor for photon and electron should not be unity.

Journal Articles

Modeling of yield estimation for DNA strand breaks based on Monte Carlo simulations of electron track structure in liquid water

Matsuya, Yusuke; Kai, Takeshi; Yoshii, Yuji*; Yachi, Yoshie*; Naijo, Shingo*; Date, Hiroyuki*; Sato, Tatsuhiko

Journal of Applied Physics, 126(12), p.124701_1 - 124701_8, 2019/09

 Times Cited Count:10 Percentile:74.82(Physics, Applied)

Biological effects after ionizing radiation exposure arise from initial DNA strand breaks. DNA damage can be estimated from the simulation with both track structure analysis and diffusion of free radicals; however, the simulation is a time-consuming process. In this study, we present a simple model for estimating yields of strand breaks based only on spatial patterns of inelastic interactions (i.e., ionization and electronic excitation) generated by electrons, which are evaluated by PHITS code without considering the production and diffusion of free radicals. In this model, the number of events per track and that of the two events pair within 3.4 nm (corresponding to 10 base pair) were stochastically sampled for calculating SSB and DSB yields, respectively. The calculated results agreed well with other simulations and experimental data on DSB yield and yield ratio of DSB/SSB for the exposure to mono-energetic electrons. The present model also can demonstrate the relative biological effectiveness at the DSB endpoint for various photon exposures. This study indicated that the spatial pattern of inelastic events composed of ionization and electronic excitation is sufficient to obtain the impact of electrons on initial induction to DNA strand break.

Journal Articles

Intensity modulated radiation fields induce protective effects and reduce importance of dose-rate effects

Matsuya, Yusuke; McMahon, S. J.*; Ghita, M.*; Yoshii, Yuji*; Sato, Tatsuhiko; Date, Hiroyuki*; Prise, K. M.*

Scientific Reports (Internet), 9(1), p.9483_1 - 9483_12, 2019/07

 Times Cited Count:6 Percentile:65.54(Multidisciplinary Sciences)

In radiotherapy, intensity modulated radiation fields and complex dose-delivery are used to prescribe doses to tumors. Here, we analyzed the impact of modulated field on radio-sensitivity and cell recovery during irradiation time. The dose was delivered to either 50% of the area of the flask containing cells (half-field) or 100% of the flask (uniform-field). We also modelled cell-killing considering dose-rate effects and intercellular signals. It is found that (i) in-field cell survival under half-field exposure is higher than uniform-field exposure even with the same dose; (ii) the importance of sub-lethal damage repair in normal human skin fibroblast cells under the half-field is reduced; (iii) the increase of cell survival under half-field is predominantly attributed to not rescue effects (increased repair) but protective effects (reduced initial DNA lesion yield). These findings provide new understanding of radio-sensitivity for hit and non-hit cells under non-uniform exposure.

Journal Articles

DNA damage induction during localized chronic exposure to an insoluble radioactive microparticle

Matsuya, Yusuke; Satou, Yukihiko; Hamada, Nobuyuki*; Date, Hiroyuki*; Ishikawa, Masayori*; Sato, Tatsuhiko

Scientific Reports (Internet), 9(1), p.10365_1 - 10365_9, 2019/07

 Times Cited Count:4 Percentile:50.91(Multidisciplinary Sciences)

Insoluble radioactive microparticles (so called Cs-bearing particles) have been assumed to adhere in the long term to trachea after aspirated into respiratory system, leading to heterogeneous dose distribution within healthy tissue around the particles. The biological effects posed by such a particle remain unclear. Here, we show cumulative DNA damage in cultured cells proximal and distal to the particle under localized chronic exposure in comparison with uniform exposure. We placed the particle-contained microcapillary onto a glass-base dish containing normal human lung cells in vitro, and observed a significant change in nuclear $$gamma$$-H2AX foci after 24 h or 48 h exposure to the particle. The dose calculation by a Monte Carlo simulation and the comparison with nuclear foci under uniform exposure suggested that the localized exposure to a Cs-bearing particle leads to not only signal-induced DNA damage to distal cells but also the reduction of DNA damage induction yield to proximal cells (protective effects). Considering the small organ dose, the conventional radiation risk assessment is adequate. This study is the first to quantify the spatial distribution of cumulative DNA lesions under heterogeneous exposure by insoluble Cs-bearing particles.

Journal Articles

Analysis of the high-dose-range radioresistance of prostate cancer cells, including cancer stem cells, based on a stochastic model

Saga, Ryo*; Matsuya, Yusuke; Takahashi, Rei*; Hasegawa, Kazuki*; Date, Hiroyuki*; Hosokawa, Yoichiro*

Journal of Radiation Research, 60(3), p.298 - 307, 2019/05

 Times Cited Count:13 Percentile:87.98(Biology)

In radiotherapy, it is recognized that cancer stem cells (CSCs) in tumor tissue shows radio-resistance. However, the relationship between content percentage of the CSCs and dose-response curve on cell survival remain unclear. In this study, we developed a stochastic model considering progeny cells and stem cells, and investigated the impact of stem cells on radio-sensitivity. From the flow-cytometric analysis (cell experiments), the content percentage of stem cells was 3.2% or less which agreed well with the model estimation from the cell survival curve. Based on the verification, it is suggested that cell survival in high-dose range is largely affected by the CSCs. In addition, regarding the sub-population of stem cells, the present model well reproduces the dose response on lethal lesions to DNA comparing with the conventional LQ model. This outcome indicates that the stem cells must be considered for describing the dose-response curve in wide dose range.

Journal Articles

New muonium HFS measurements at J-PARC/MUSE

Strasser, P.*; Aoki, Masaharu*; Fukao, Yoshinori*; Higashi, Yoshitaka*; Higuchi, Takashi*; Iinuma, Hiromi*; Ikedo, Yutaka*; Ishida, Keiichi*; Ito, Takashi; Iwasaki, Masahiko*; et al.

Hyperfine Interactions, 237(1), p.124_1 - 124_9, 2016/12

 Times Cited Count:6 Percentile:92.96

Journal Articles

A Parameter study of pencil beam proton dose distributions for the treatment of ocular melanoma utilizing spot scanning

Sutherland, K.*; Miyajima, Satoshi*; Date, Hiroyuki*; Shirato, Hiroki*; Ishikawa, Masayori*; Murakami, Masao*; Yamagiwa, Mitsuru; Bolton, P.; Tajima, Toshiki

Radiological Physics and Technology, 3(1), p.16 - 22, 2010/01

Journal Articles

Compact DEMO, SlimCS; Design progress and issues

Tobita, Kenji; Nishio, Satoshi; Enoeda, Mikio; Kawashima, Hisato; Kurita, Genichi; Tanigawa, Hiroyasu; Nakamura, Hirofumi; Honda, Mitsuru; Saito, Ai*; Sato, Satoshi; et al.

Nuclear Fusion, 49(7), p.075029_1 - 075029_10, 2009/07

 Times Cited Count:125 Percentile:98.18(Physics, Fluids & Plasmas)

Recent design study on SlimCS focused mainly on the torus configuration including blanket, divertor, materials and maintenance scheme. For vertical stability of elongated plasma and high beta access, a sector-wide conducting shell is arranged in between replaceable and permanent blanket. The reactor adopts pressurized-water-cooled solid breeding blanket. Compared with the previous advanced concept with supercritical water, the design options satisfying tritium self-sufficiency are relatively scarce. Considered divertor technology and materials, an allowable heat load to the divertor plate should be 8 MW/m$$^{2}$$ or lower, which can be a critical constraint for determining a handling power of DEMO (a combination of alpha heating power and external input power for current drive).

Journal Articles

Super-parallel simulation systems for sophisticated radiation therapy

Saito, Kimiaki; Saito, Hidetoshi*; Kunieda, Etsuo*; Narita, Yuichiro*; Myojoyama, Atsushi*; Fujisaki, Tatsuya*; Kawase, Takatsugu*; Kaneko, Katsutaro*; Ozaki, Masahiro*; Deloar, H. M.*; et al.

Joho Shori, 48(10), p.1081 - 1088, 2007/10

no abstracts in English

Journal Articles

Micro-impact damage caused by mercury bubble collapse

Futakawa, Masatoshi; Naoe, Takashi*; Kogawa, Hiroyuki; Date, Hidefumi*; Ikeda, Yujiro

JSME International Journal, Series A, 48(4), p.234 - 239, 2005/10

Mercury target will be installed at the material science and life facility in J-PARC, which will promote innovative science. The mercury target will be subjected to the pressure wave caused by proton bombarding in the mercury. The pressure wave propagation induces the cavitation in mercury that imposes localized impact damage on the target vessel. The impact erosion is a critical issue to decide the lifetime of target. An electromagnetic impact testing machine, MIMTM, was developed to reproduce the localized impact erosion damage and evaluate the damage formation. Additionally, droplet impact analyses were carried out to investigate the correlation between isolate pit profile and micro-jet velocity. We confirmed that the value of depth/radius was applicable to estimate micro-jet velocity, and the velocity at 560 W in MIMTM equivalent to 1MW proton beam injection was 300 m/s approximately.

Journal Articles

Pitting damage by pressure waves in a mercury target

Futakawa, Masatoshi; Naoe, Takashi; Tsai, C.-C.*; Kogawa, Hiroyuki; Ishikura, Shuichi*; Ikeda, Yujiro; Soyama, Hitoshi*; Date, Hidefumi*

Journal of Nuclear Materials, 343(1-3), p.70 - 80, 2005/08

 Times Cited Count:54 Percentile:95.91(Materials Science, Multidisciplinary)

no abstracts in English

Journal Articles

Aging deterioration test of seismic isolation applied to fusion experimental reactor

Takeda, Nobukazu; Nakahira, Masataka; Kakudate, Satoshi; Takahashi, Hiroyuki*; Shibanuma, Kiyoshi; Yabana, Shuichi*; Matsuda, Akihiro*

Proceedings of 9th World Seminar on Seismic Isolation, Energy Dissipation and Active Vibration Control of Structures (CD-ROM), p.299 - 306, 2005/00

For the ITER, a fusion experimental reactor, it is planned to use rubber bearings in order to enhance the reliability of integrity with a sufficient margin even for the earthquakes beyond the design basis earthquake. In application for nuclear plants, the vertical compression of the isolator is 2$$sim$$5 MPa and there is no experience for such a high compression as 10 MPa to be used for the ITER. Therefore, there is not enough design data of the rubber bearings with high compression, and thus a detailed estimation of performance is necessary. As a result of the endurance test after aging, it was validated that the bearing can be applied safely until 400th cycle even after 40 years of aging. On the other hand, the residual deformation was found at the 246th cycle. This means that the residual deformation can be observed enough earlier than the change of the macroscopic mechanical parameter such as stiffness. Therefore, it is possible to prevent break of the bearing during operation by sensing a sign of break with a periodical visual inspection.

Journal Articles

Hardening effect on impact erosion in interface between liquid and solid metals

Futakawa, Masatoshi; Naoe, Takashi*; Kogawa, Hiroyuki; Ishikura, Shuichi*; Date, Hidefumi*

Zairyo, 53(3), p.283 - 288, 2004/03

no abstracts in English

Journal Articles

Erosion damage on solid boundaries in contact with liquid metals by impulsive pressure injection

Futakawa, Masatoshi; Kogawa, Hiroyuki; Hino, Ryutaro; Date, Hidefumi*; Takeishi, Hiromasa*

International Journal of Impact Engineering, 28(2), p.123 - 135, 2003/02

JAERI is carrying out research & development to construct the a of spallation neutron source facility, which may bring us innovative science fields. A high power proton beam will be injected into a liquid mercury target to produce neutrons. The mercury vessel will consequently be subjected to the pressure waves generated by rapid thermal expansion. The pressure waves will propagate from the liquid mercury into the vessel solid metal, and back again. The pressure waves may induce erosion at the interface between the solid metal vessel and the liquid mercury under certain loading conditions, e.g. impact. In order to investigate the impact erosion damage due to the pressure wave, we have carried out impact experiments using a modified conventional split Hopkinson pressure bar apparatus on mercury filling a small chamber. Surface degradation in the form of many pits was observed and the ranking order of damage was found to be A6061$$>$$316SS@Inconel600$$>$$Maraging steel, which is the same as that of hardness.

JAEA Reports

Design study on core characteristics of sodium cooled fast reactors; Mixed oxide fuel cores

Yamadate, Megumi; Yamaguchi, Hiroyuki; Naganuma, Masayuki; Mizuno, Tomoyasu; Takaki, Naoyuki

JNC TN9400 2002-065, 131 Pages, 2002/12


Phase-II of the Feasibility Study on Commercialized Fast Reactor Cycle System in Japan (F/S) has been started since April 2001 and the design studies of various FR and recycle concepts are being conducted. In this report the JFY2001 studies of sodium cooled FR with mixed oxide fuel are summarized. The main results are as following. (1) Large scale reactors (1,500 MWe) (a) As for the large scale homogeneous ABLE type fuel core, we aimed to improve the effective average burn-up (that includes contribution of blankets) in order to reduce the fuel cycle cost. The specifications of Phase-I core and fuel were modified, which results in reducing the numbers of radial blanket sub-assemblies. As a result, the effective average burn-up was improved from 63 GWd/t to 77GWd/t. (b) As for the inner-duct sub-assembly core, the thickness of inner-duct was decided according to the evaluation of inner-duct expansion. As a result, the core reveals greater burn-up swing by about 0.6% $$Delta$$k/kk' than that of the ABLE type fuel core. (c) As for the heterogeneous core, the inner-blanket shuffling concept was studied in order to improve the effective average burn-up and the thermal hydraulic characteristics, As a result, though the breeding ratio decreases in some extent, the possible improvement is obtained in the effective average burn-up (from 56 GWd/t to 80 GWd/t) and core thermal hydraulic design. (2) Medium scale reactors (500 MWe) (a) As for the medium scale core, with the aim of an attractive core concept the high internal conversion ration core was studied. As a result, the obtained typical core concept reveals around 1.05 of breeding ratio with core diameter 10% greater than conventional one and without radial blanket. The core achieves over 100 GWd/t of the effective average burn-up with the potential capability of long operation cycle.

Journal Articles

Thermal shock analysis of liquid-mercury spallation target

Ishikura, Shuichi*; Kogawa, Hiroyuki; Futakawa, Masatoshi; Hino, Ryutaro; Date, Hidefumi*

Koon Gakkai-Shi, 28(6), p.329 - 335, 2002/11

The developments of the neutron scattering facilities are carried out under the high-intensity proton accelerator project promoted by JAERI and KEK. To estimate the structural integrity of the heavy liquid-metal (Hg) target used as a spallation neutron source in a MW-class neutron scattering facility, dynamic stress behavior due to the incident of a 1MW-pulsed proton beam were analyzed by using FEM code. Two-type target containers with semi-cylindrical type and flat-plate type window were used as models for analyses. As a result, it is confirmed that the stress (pressure wave) generated by dynamic thermal shock becomes the largest at the center of window, and the flat-plate type window is more advantageous from the structural viewpoint than the semi-cylindrical type window. It has been understood that the stress generated in the window by the pressure wave can be treated as the secondary stress.

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