Translational study for stereotactic body radiotherapy against non-small cell lung cancer, including oligometastases, considering cancer stem-like cells enable predicting clinical outcome from data

Saga, Ryo*; Matsuya, Yusuke; Sato, Hikari*; Hasegawa, Kazuki*; Obara, Hideki*; Komai, Fumio*; Yoshino, Hironori*; Aoki, Masahiko*; Hosokawa, Yoichiro*

Radiotherapy and Oncology, p.109444_1 - 109444_9, 2023/00

https://doi.org/10.1016/j.radonc.2022.109444

When treating non-small cell lung cancer (NSCLC), stereotactic body radiotherapy (SBRT) with high-dose irradiation is often utilized. The fractionation schemes and curative effects can be evaluated by mathematical models for predicting cell survival curve. Such model parameters can be determined from in vitro experiment, but they are empirically determined based on experiences in clinics. As such, there is a large gap between in vitro and clinical study. As such background, translational study between in vitro cell survival and clinical curative effects is necessary. In this study, explicitly considering existence of cancer stem-like cells (CSCs), we developed an all-in-one model for predicting both in vitro cell survival and clinical curative effects (integrated microdosimetric-kinetic (IMK) model) and performed retrospective evaluation of clinical outcomes following SBRT for NSCLC in Hirosaki University Hospital. As a result, the IMK model successfully reproduced both in vitro cell survival and the tumor control probability with various fractionation schemes (i.e., 6-10 Gy per fraction). The developed model would contribute on precisely understanding the impact of CSCs on curative effects after SBRT for NSCLC with high precision.

Quasifree neutron knockout reaction reveals a small -Orbital component in the Borromean nucleus B

Yang, Z. H.*; Kubota, Yuki*; Corsi, A.*; Yoshida, Kazuki; Sun, X.-X.*; Li, J. G.*; Kimura, Masaaki*; Michel, N.*; Ogata, Kazuyuki*; Yuan, C. X.*; et al.

Physical Review Letters, 126(8), p.082501_1 - 082501_8, 2021/02

AA2020-0819.pdf:1.29MB

https://doi.org/10.1103/PhysRevLett.126.082501

A quasifree (,) experiment was performed to study the structure of the Borromean nucleus B, which had long been considered to have a neutron halo. By analyzing the momentum distributions and exclusive cross sections, we obtained the spectroscopic factors for and orbitals, and a surprisingly small percentage of 9(2)% was determined for . Our finding of such a small component and the halo features reported in prior experiments can be explained by the deformed relativistic Hartree-Bogoliubov theory in continuum, revealing a definite but not dominant neutron halo in B. The present work gives the smallest - or -orbital component among known nuclei exhibiting halo features and implies that the dominant occupation of or orbitals is not a prerequisite for the occurrence of a neutron halo.

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

https://doi.org/10.1093/jrr/rrz011

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.

Utilization of actinide as cell active materials; Effective utilization of uranium as battery active material, JAERI's nuclear research promotion program, H10-034-2 (Contract research)

Yamana, Hajimu*; Moriyama, Hirotake*; Asano, Hideki*; Shiokawa, Yoshinobu*; Yamamura, Tomoo*; Hasegawa, Kazuki*; Kimura, Akihiro*; Umekita, Satoshi*

JAERI-Tech 2002-018, 33 Pages, 2002/03

JAERI-Tech-2002-018.pdf:1.95MB

no abstracts in English

Upgrading and achievements in the industrial analysis beamline BL05

Hasegawa, Takayuki*; Uemura, Masaharu*; Takueuchi, Kazuki*; Kodaka, Takuya*; Fukada, Noboru*; Umesaki, Norimasa*; Fukushima, Sei*; Teraoka, Yuden; Haruyama, Yuichi*; Niibe, Masahito*; et al.

no journal, , 

no abstracts in English

CRIEPI-JAEA collaboration study on mass transport by groundwater in and around the Mizunami Underground Research Laboratory

Hasegawa, Takuma*; Nakata, Kotaro*; Tomioka, Yuichi*; Ota, Tomoko*; Hama, Katsuhiro; Iwatsuki, Teruki; Kato, Toshihiro*; Hayashida, Kazuki

no journal, , 

no abstracts in English

Investigation of radiosensitivity enhanced by inflammatory responses after irradiation based on a cell-killing model considering non-targeted effects

Takahashi, Rei*; Saga, Ryo*; Matsuya, Yusuke; Hasegawa, Kazuki*; Fukui, Roman*; Hosokawa, Yoichiro*

no journal, , 

Inflammatory responses after irradiation induce antioxidant activity, leading to radioresistance in cancer cells. In our previous study, it was found that a hyaluronan synthesis inhibitor (4-MU) can suppress inflammatory responses, however the underlying mechanisms are still unknown. In this study, we aimed to clarify the radiosensitization mechanism induced by 4-MU in the application of cell-killing models. In terms of in vitro experiments, cultured human fibrosarcoma cells were exposed to X-rays in presence of 100 M 4-MU and scavenger of intercellular signalling (1% DMSO, 40 M c-PTIO), and we measured the relation between dose and cell viability by means of colony assay. The experimental results were also interpreted by using integrated cell-killing model which has been developed so as to consider non-targeted effects. From the experiments, it was found that a combination of 4-MU treatment and irradiation significantly reduced the cell survival. This reduced viability was suppressed in the presence of DMSO or c-TPIO. Meanwhile, the model analysis showed such an increase of cell-killing is predominantly attributed by non-targeted effects. These results suggest that the radiosensetization promoted by 4-MU treatment is predominantly attributed to the accumulation in non-targeted effects.