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We have established an experimental scheme to evaluate the repair efficiency of non-DSB type of clustered DNA damage (hereafter clustered damage). Fluorescent protein (EGFP) expression rates were examined as an indicator of the repair efficiency after introducing irradiated EGFP plasmids DNA into non-irradiated human cells [1]. Using this scheme, we revealed that the repair efficiency decreased with increasing absorbed dose even with low LET irradiation, suggesting that the caused the clustered damage significantly compromised DNA repair processes [2]. Furthermore, it is becoming clear that, even by the same absorbed dose, C6+ ions with high LET induce certain fraction of hardly repairable damage. We currently try further to develop a method using a novel plasmid construct. The plasmid DNA has two fluorescent protein expression genes at different multi-cloning sites. The radiation damage region could be limited only to one of the isolated fluorescent protein genes as a clipping fragment from the vector. After recombining the irradiated fragment gene to the vector, the full-length plasmid is then transfected into non-irradiated cells. The observed difference in the expression levels of the two fluorescent proteins co-expressed indicates the repair efficiency. This makes it possible to analyze real-time dynamics of the repair efficiency with taking into account the transformation frequency. We will present current progresses of test experiments using this concept. [1] Nakaue, Obata, et al. Radiat. Prot. Dosimetry. 183, 79-83 (2019) [2] Obata, et al. ICRR2019, Manchester, UK, Aug. 29-25, (2019), 日本放射線影響学会第63回大会

The last year we reported the enhancement of cell-killing effect irradiated with carbon ions by applying longitudinal magnetic field. This year we examined the mechanism of the effect, focusing on cellular response(s) via gap-junction mediated cell-cell communication. Normal human skin fibroblasts and cervical epitheloid carcinoma cells were irradiated with carbon ions (350MeV/n, LET~12keV/µm) accelerated with the Heavy Ion Medical Accelerator in Chiba under the longitudinal magnetic field (0.6T) with or without a specific inhibitor of gap junction (40 µM of gamma-isomer of hexachloro-cyclohexane). The cell-killing effects treated with the magnetic field were 1.3 ~ 1.5 times higher than those of carbon ion alone. When using the gap-junction inhibitor, the cell-killing effects were enhanced as the same level among the magnetic field alone, the gap-junction inhibitor alone and both treatments. There is evidence that the enhanced effect by the longitudinal magnetic fields is induced by cellular response(s) via gap-junction mediated cell-cell communication. (This is the co-operative study with Drs.T.Inaniwa, N.Usami, S.Sato, A.Noda, M.Muramatsu, Y.Iwata, N.Kanematsu, T.Shirai, K.Noda), 第79回日本癌学会学術総会

Purpose: The clinical dose in carbon ion radiotherapy with wobbler method at National Institute of Radiological Sciences in Japan is defined by calculating the biological dose based on RBE for human salivary gland (HSG) cells, and normalizing it to the clinical RBE value obtained by neutron radiotherapy. However, irradiated various tumors and normal tissues are actually different from HSG cells. Therefore, the predicted biological dose for irradiated field may have large uncertainty. In order to estimate the RBE for various cells, we introduced radiobiological computation software ‘Survival’, and tried to calculate the RBE using the ‘Survival’ for three typical cells irradiated by each ions. Methods: We used the biological dose analysis software ‘Survival’. Particle Irradiation Data Ensemble (PIDE) ver.3.2 was used as literature data on past cell irradiation. RBE (RBESurvival) values were calculated by analyzing cell survival rate with the ‘Survival’ using PIDE irradiation conditions. Microdosimetric Kinetic Model (MKM) as a biological effect model was used in this study. The target cells were HSG, V79 and CHO cells, and the irradiated particles were 12C, 20Ne, and 3He. The linear energy transfer (dose averaged LET: LETD) described in PIDE was used. By comparing these with RBE (RBEPIDE) values obtained from the PIDE, the RBE values calculated by using the ‘Survival’ was evaluated. Results: We calculated the RBE values for HSG, V79 and CHO cells irradiated by 12C, 20Ne, and 3He ions by using the ‘Survival’. The RBESurvival values were generally consistent with RBEPIDE values for them. Conclusion: RBE calculations by using the ‘Survival’ for HSG, V79 and CHO cells irradiated by 12C, 20Ne, and 3He ions were evaluated in this study. The ‘Survival’ could roughly estimate the RBE for three typical cells. In the future, we will evaluate the RBE calculation accuracy of the ‘Survival’ for various cells., AAPM2020

[Purpose] The clinical dose in heavy ion radiotherapy is defined by calculating the biological dose based on RBE for human salivary gland (HSG) cells, and normalizing it to the clinical RBE value obtained by neutron radiotherapy. However, since irradiated various tumors and normal tissues are not HSG cells, the predicted biological dose for irradiated field may have large uncertainty. In this study, we introduced radiobiological computation software ‘Survival’ to estimate the RBE for various cells, and tried to calculate the RBE using ‘Survival’ for irradiation of HSG cells with 12C, 20Ne and 3He, ions. [Methods] The biological dose analysis software used was ‘Survival'. PIDE ver.3.1 was used as literature data on past cell irradiation. RBE (RBESurvival) was calculated by analyzing cell survival rate with the ‘Survival’ using PEID irradiation conditions. By comparing this with RBE(RBEPEID) calculated from PEID, the accuracy of RBE calculation using the ‘Survival’ was evaluated. Microdosimetric Kinetic Model (MKM) was used for the biological effect model, and the values of each parameter required were those of previous studies. The target cells were HSG, and the irradiated particles were 12C, 20Ne, and 3He. The linear energy transfer (dose averaged LET: LETD) described in PIDE was used. [Results] RBESurvival was generally consistent with RBEPEID. This suggests that RBE can be roughly estimated. The area where RBESurvival cannot reproduce RBEPEID was different for each particle. Also, the relationship with LET is not shown. [Conclusion] The ‘Survival’ roughly could estimate the RBE for irradiation of HSG cells with 12C, 20Ne and 3He, ions. In the future, we will evaluate the RBE calculation accuracy of the ‘Survival’ for various cells., 第119回日本医学物理学会学術大会

Microdosimetry with the microdosimetric kinetic (MK) model is a method to estimate the biological effects of the radiations which measures the dose absorbed by a micrometer-sized volume, namely a specific energy. The MK model developed by National Institute of Radiological Sciences (NIRS) is currently the world's standard biological model for calculating biological effects of therapeutic carbon-ion beams. NIRS recently announced a multi-ion treatment plan to produce better tumor outcomes from increasing the LET in tumors. A recent study on the concept and modeling of multi-ion therapy has been reported, which will use helium, carbon, oxygen and neon ions to treat pancreatic cancer. This study estimates the survival fraction of SOBP of scanning helium ions using the microdoimetric method., MMND-ITRO 2020

To date, more than 10,000 patients of various tumour sites have been treated with therapeutic carbon-ion beams at the National Institute of Radiological Sciences (NIRS). In carbon-ion radiotherapy treatment planning, the biological effectiveness of the therapeutic beams has to be predicted based on one of biological models. The microdosimetric kinetic (MK) model1'2 has been used for this purpose at the NIRS. For further development of heavy-ion radiotherapy, we started a research project of a hypo-fractionated multi-ion radiotherapy, termed as a "Quantum Knife". In the Quantum Knife, heavy ions up to neon are assumed as therapeutic ion species. Recent study revealed that the MK model may overestimate the biological effectiveness of heavy ions with linear energy transfer (LET) > 150 keV/^m, especially at high dose region.3 Thus, the MK model should be updated so that it is applicable in treatment planning of the quantum knife. In this study, a biological model, namely a stochastic microdosimetric kinetic (SMK) model, will be reviewed and tested for in-vitro cell-survival fraction data., Mini- Micro- Nano- Dosimetry (MMND) 2020

Objectives/Interrogation: Recently, there are plenty of commercial external fixators for hand fractures. However, they are difficult to adjust after application. The ideal external fixator in hand is low profile and adequately rigid for early mobilization, and easy to apply and modify. We developed[for full text, please go to the a.m. URL], 14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT)

The nonunion of distal phalangeal communized fracture is relatively rare in hand fractures. However, if it occurred, the surgical treatment is quite difficult because of small piece of fragmentations. We developed a new fixation method that involves the insertion of two wires and external wire compression fixation using a metal clamp. The aim of this technique was to increase the compression force between fragments and rigidity of conventional percutaneous Kirschner wire fixation. Here, we present a patient with the nonunion of distal phalangeal communized fracture who was satisfactorily treated with open reduction and percutaneous interfragmentary compression fixation with a linking external wire fixator (the Ichi-Fixator system). Such a treatment that enables compression fixation for communized distal phalangeal fracture of nonunion will clearly boost bone healing. Linked external wire-type compression fixator (the Ichi-Fixator system) enables enhanced security of fixation and facilitates the bone healing.

第20回宇宙科学シンポジウム (2020年1月8日-9日. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)相模原キャンパス), 相模原市, 神奈川県, 20th Space Science Symposium (January 8-9, 2020. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS)Sagamihara Campus), Sagamihara, Kanagawa Japan, 資料番号: SA6000152020, レポート番号: S5-004

Glioblastoma (GBM), a Grade IV brain tumour, is a well-known radioresistant cancer. To investigate one of the causes of radioresistance, we studied the capacity for potential lethal damage repair (PLDR) of three altered strains of GBM: T98G, U87 and LN18, irradiated with various ions and various levels of linear energy transfer (LET). The GBM cells were exposed to 12C and 28Si ion beams with LETs of 55, 100 and 200 keV/μm, and with X-ray beams of 1.7 keV/μm. Mono-energetic 12C ions and 28Si ions were generated by the Heavy Ion Medical Accelerator at the National Institute of Radiological Science, Chiba, Japan. Clonogenic assays were used to determine cell inactivation. The ability of the cells to repair potential lethal damage was demonstrated by allowing one identical set of irradiated cells to repair for 24 h before subplating. The results show there is definite PLDR with X-rays, some evidence of PLDR at 55 keV/μm, and minimal PLDR at 100 keV/μm. There is no observable PLDR at 200 keV/μm. This is the first study, to the authors' knowledge, demonstrating the capability of GBM cells to repair potential lethal damage following charged ion irradiations. It is concluded that a GBM's PLDR is dependent on LET, dose and GBM strain; and the more radioresistant the cell strain, the greater the PLDR.

Tumors that overexpress the receptor tyrosine kinase HER2 (HER2-positive tumors) tend to be higher grade tumors that are more likely to spread and thus are more aggressive than other types of breast cancers (BCs). In this study we investigated whether carbon-ion beam alone, or in combination with lapatinib, has a beneficial effect in targeting HER2-positive breast cancer stem-like cells (CSCs) compared to that of X-rays. Spheroid formation assays confirmed that ESA+/CD24- cells have CSC properties compared to ESA-/CD24+ cells. We found that CSCs were more highly enriched after X-ray irradiation combined with lapatinib, whereas carbon-ion beam combined with lapatinib significantly decreased the proportion of CSCs. Carbon-ion beam combined with lapatinib significantly enhanced apoptosis-related expression of caspase-3 compared to carbon-ion beam alone, X-rays alone, or X-rays combined with lapatinib. In conclusion, carbon ion beam combined with lapatinib has high potential to eliminate breast CSCs with enhanced apoptosis.