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Matsuya, Yusuke; Sato, Tatsuhiko; Kusumoto, Tamon*; Yachi, Yoshie*; Seino, Ryosuke*; Miwa, Misako*; Ishikawa, Masayori*; Matsuyama, Shigeo*; Fukunaga, Hisanori*
Scientific Reports (Internet), 14, p.16696_1 - 16696_14, 2024/07
Times Cited Count:2Boron neutron capture therapy (BNCT) is a unique radiotherapy to selectively eradicate tumor cells using boron compounds (e.g., 4-borono-L-phenylalanine [BPA]) that are heterogeneously taken up at the cellular level. However, the impacts of tempo-spatial heterogenicity on cell killing remain unclear. With the technical combination of radiation track detector, cell cycle analysis, and biophysical simulations, we demonstrated the cell cycle-dependent heterogenicity of BPA uptake and following biological impacts of B(n,
)
Li reactions in HeLa cells expressing Fluorescent Ubiquitination-based Cell Cycle Indicators (FUCCI), as well as its modification effects of polyvinyl alcohol (PVA). As a result, we revealed that the intracellular BPA concentration in the S/G2/M phase was higher than that in the G1/S phase and that PVA modified the cell cycle dependence. Further, these findings lead to the development of the first BPA-PVA-based model for predicting BNCT treatment effects. These outcomes may contribute to more precision of therapeutic efficacy, when BNCT is combined with PVA and/or cell cycle-specific anticancer agents.
Matsuya, Yusuke; Kusumoto, Tamon*; Yachi, Yoshie*; Hirata, Yuho; Miwa, Misako*; Ishikawa, Masayori*; Date, Hiroyuki*; Iwamoto, Yosuke; Matsuyama, Shigeo*; Fukunaga, Hisanori*
AIP Advances (Internet), 12(2), p.025013_1 - 025013_9, 2022/02
Times Cited Count:7 Percentile:54.70(Nanoscience & Nanotechnology)Boron Neutron Capture Therapy (BNCT) is a radiation therapy, which can selectively eradicate solid tumors by -particles and Li ions generated through the nuclear reaction between thermal neutron and
B in tumor cells. With the development of accelerator-based neutron sources that can be installed in medical institutions, accelerator-based boron neutron capture therapy is expected to become available at several medical institutes around the world in the near future. Lithium is one of the targets that can produce thermal neutrons from the
Li(p,n)
Be near-threshold reaction. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo code, which can simulate a variety of diverse particle types and nuclear reactions. The latest PHITS code enables simulating the generation of neutrons from the
Li(p,n)
Be reactions by using Japanese Evaluated Nuclear Data Library (JENDL-4.0/HE). In this study, we evaluated the neutron fluence using the PHITS code by comparing it to reference data. The subsequent neutron transport simulations were also performed to evaluate the boron trifluoride (BF
) detector responses and the recoiled proton fluence detected by a CR-39 plastic detector. As a result, these comparative studies confirmed that the PHITS code can accurately simulate neutrons generated from an accelerator using a Li target. The PHITS code has a significant potential for contributing to more precise evaluating accelerator-based neutron fields and understandings of therapeutic effects of BNCT.
Matsuya, Yusuke; Hamada, Nobuyuki*; Yachi, Yoshie*; Satou, Yukihiko; Ishikawa, Masayori*; Date, Hiroyuki*; Sato, Tatsuhiko
Cancers (Internet), 14(4), p.1045_1 - 1045_15, 2022/02
Times Cited Count:12 Percentile:80.83(Oncology)An insoluble cesium-bearing microparticle (Cs-BMP) was discovered after the incident at the Fukushima nuclear power plant. Radiation risk by intake of internal exposure to radioactive cesium is conventionally estimated from organ dose, assuming that soluble cesium is uniformly distributed throughout human body. Meanwhile, such Cs-BMPs are assumed to adhere in the long term to normal tissue, leading to chronic non-uniform exposure. In this study, to clarify the normal tissue effects for Cs-BMP exposure, we investigated the relationship between the inflammatory responses and DNA damage induction. From experiments focusing on the inflammatory signaling pathways such as NF-B p65 and COX-2, compared to the uniform exposure to
-rays, NF-
B p65 tended to be more activated in the cells proximal to the Cs-BMP, while both NF-
B p65 and COX-2 were significantly activated in the distal cells. Experiments with inhibitors for NF-
B p65 and COX-2 suggested involvement of such inflammatory responses both in the reduced radiosensitivity of the cells proximal to Cs-BMP and the enhanced radiosensitivity of the cells distal from Cs-BMP. These results suggested that radiation effects for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.
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:6 Percentile:43.89(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.
Kusumoto, Tamon*; Matsuya, Yusuke; Baba, Kentaro*; Ogawara, Ryo*; Akselrod, M. S.*; Harrison, J.*; Fomenko, V.*; Kai, Takeshi; Ishikawa, Masayori*; Hasegawa, Sumitaka*; et al.
Radiation Measurements, 132, p.106256_1 - 106256_4, 2020/03
Times Cited Count:8 Percentile:58.60(Nuclear Science & Technology)Internal radiation therapy with Cu-64 concentrates energy deposition in tumor cells by virtue of released Auger electrons with low energy. In our previous study, we have attached the solutions at the surface of Fluorescent Nuclear Track Detector (FNTD) and succeeded in measuring the absorbed doses of Auger electrons registered in FNTD. However, because there are several types of radiation emitted from the source, i.e., beta rays, positron etc., the contribution degree of Auger electron to energy concentration remain uncertain. In this study, we quantitatively analyzed the spatial dose distribution in the FNTD based on Monte Carlo simulation with PHITS and GEANT4, and evaluated high dose deposited by Auger electrons. The dose distribution calculated by the PHITS code is exactly equivalent to that by Geant4. Also, the simulations are well agreement with experimental results. If the contribution of Auger electrons is ignored, the significantly high absorbed dose proximal to the source is not properly reduced. These findings demonstrate that Auger electrons work very effectively to kill cancer cells proximal to Cu-64 source while minimizing damage effects on normal cells distal to the source.
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:12 Percentile:56.88(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 -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.
Tsuda, Shuichi; Yoshida, Tadayoshi; Nakahara, Yukio; Sato, Tetsuro; Seki, Akiyuki; Matsuda, Norihiro; Ando, Masaki; Takemiya, Hiroshi; Tanigaki, Minoru*; Takamiya, Koichi*; et al.
JAEA-Technology 2013-037, 54 Pages, 2013/10
JAEA has been performing dose rate mapping in air using a car-borne survey system KURAMA-II. The KURAMA system is a GPS-aided mobile radiation monitoring system that has been newly developed by Kyoto University Research Reactor Institute in response to the nuclear disaster. The KURAMA system is composed of an energy-compensated scintillation survey meter for measuring dose rate, electric device for controlling both the dose rates and the position data from a GPS module, a computer server for processing and analyzing data from KURAMA, and client PCs for providing for end users. The KURAMA-II has been improved in small-packaging, durability, and automated data transmission. In consequence, dose rate mapping in wide area has become possible in shorter period of time. This report describes the construction of KURAMA-II, its application and a suggestion of how to manage a large number of KURAMA-II.
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
Komeda, Masao; Kumada, Hiroaki; Ishikawa, Masayori*; Nakamura, Takemi; Yamamoto, Kazuyoshi; Matsumura, Akira*
Applied Radiation and Isotopes, 67(7-8, Suppl.), p.S254 - S257, 2009/07
Times Cited Count:7 Percentile:44.17(Chemistry, Inorganic & Nuclear)Komeda, Masao; Kumada, Hiroaki; Ishikawa, Masayori*; Nakamura, Takemi; Yamamoto, Kazuyoshi; Matsumura, Akira*
Proceedings of 13th International Congress on Neutron Capture Therapy (ICNCT-13) (CD-ROM), 3 Pages, 2008/11
In this report, deterioration of a SOF detector that can measure thermal neutron in real time was investigated in irradiation experiments. Sensitivity of a SOF detector decreased by 2.0% after an irradiation of about 4 hours. Then thermal neutron fluence was approximately 2.010
(n/cm
). And after the SOF detector was used for about 2 months, sensitivity decreased to 42%. Then thermal neutron fluence was approximately 6.4
10
(n/cm
). Supposing that thermal neutron fluence is 2
10
(n/cm
) on the surface of a patient at a BNCT, sensitivity of a SOF detector is considered to be decreased by approximately 0.3% at a BNCT. Therefore it is considered that countermeasure against deterioration is necessary for using a SOF detector at BNCT in the future.
Ishikawa, Masayori*; Ono, Koji*; Matsumura, Akira*; Yamamoto, Tetsuya*; Hiratsuka, Junichi*; Miyatake, Shinichi*; Kato, Itsuro*; Sakurai, Yoshinori*; Kobayashi, Toru*; Kumada, Hiroaki; et al.
Proceedings of 12th International Congress on Neutron Capture Therapy (ICNCT-12), p.397 - 400, 2006/10
An ultraminiature thermal neutron monitor which was named SOF detector (Scintillator with Optical Fiber detector) had been developed for BNCT treatment. We had been experienced 15 clinical trials using SOF detector until the end of 2005, some measurements got good results, and some got unacceptable results. One reason of the unacceptable results was due to dislocation of the detector during treatment. This is because it is difficult to fix the SOF detector on patient's skin without strong sticker. To overcome this problem, a loop-type SOF probe was developed. By using the loop-type SOF detector, fixing on the patient's skin was much easier.
Ishikawa, Masayori*; Kumada, Hiroaki; Yamamoto, Kazuyoshi; Kaneko, Junichi*; Bengua, G.*; Unesaki, Hironobu*; Sakurai, Yoshinori*; Tanaka, Kenichi*; Kosako, Toshiso*
Nuclear Instruments and Methods in Physics Research A, 551(2-3), p.448 - 457, 2005/10
Times Cited Count:12 Percentile:63.52(Instruments & Instrumentation)A wide range thermal neutron detector was developed based on the Scintillator with Optical Fiber (SOF) detector which has been previously used for thermal neutron monitoring during boron neutron capture therapy irradiation. With this new detector system we intended to address the issues of real-time thermal neutron flux measurement and the simultaneous measurement of a wide range of thermal neutron flux in a BNCT irradiation field which were difficult to implement with the gold wire activation method. A good agreement between the thermal neutron flux measured by the gold wire activation method and the paired SOF detector system was observed. However, measurements which would normally take a few days to perform with the gold wire activation method were obtained in just about 15 min using the SOF detector system. We also confirmed the dynamic range of linearity for the SOF detector system to be in the order of magnitude of 1e-4.
Matsuya, Yusuke; Satou, Yukihiko; Hamada, Nobuyuki*; Date, Hiroyuki*; Ishikawa, Masayori*; Sato, Tatsuhiko
no journal, ,
Following the incident at the Fukushima Dai-ichi Nuclear Power Station (F1NPS) in 2011, insoluble radioactive microparticles (so called Cs-bearing particle) have been found in the land area around F1NPS. The energy deposition by such a particle is localized mainly by -rays in cells close to a Cs-bearing particle. There is no literature on the biological effects after such particle exposures. Here, we investigated DNA lesions after long-term exposure to a Cs-bearing particle in comparison with a uniform exposure to Cs-137
-rays. From dose calculation by a Monte Carlo simulation and the experiments in vitro, the several DNA lesions in the cells distal to the particle and the less lesions induction in the cells close to the particle were observed in the comparison with the uniform exposure. The increase of lesions in number was suppressed by 1% DMSO, suggesting the involvement of reactive oxygen species. Considering the small organ dose, the conventional radiation risk assessment is adequate. This study is the first to quantify the relationship between absorbed dose-rate and nuclear DNA damage under long-term heterogeneous exposure to a Cs-bearing particle.
Kumada, Hiroaki; Ishikawa, Masayori*; Komeda, Masao; Nakamura, Takemi; Yamamoto, Kazuyoshi; Nakagawa, Yoshinobu*
no journal, ,
no abstracts in English