Faculty Profiles - HANAFUSA Tadashi

Papers - HANAFUSA Tadashi

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The current status and novel advances of boron neutron capture therapy clinical trials. International journal

Tianyun Zhou, Kazuyo Igawa, Tomonari Kasai, Takuya Sadahira, Wei Wang, Tomofumi Watanabe, Kensuke Bekku, Satoshi Katayama, Takehiro Iwata, Tadashi Hanafusa, Abai Xu, Motoo Araki, Hiroyuki Michiue, Peng Huang

American journal of cancer research 14 ( 2 ) 429 - 447 2024

Language：English Publishing type：Research paper (scientific journal)

Boron neutron capture therapy (BNCT) is a treatment method that focuses on improving the cure rate of patients with cancer who are difficult to treat using traditional clinical methods. By utilizing the high neutron absorption cross-section of boron, material rich in boron inside tumor cells can absorb neutrons and release high-energy ions, thereby destroying tumor cells. Owing to the short range of alpha particles, this method can precisely target tumor cells while minimizing the inflicted damage to the surrounding normal tissues, making it a potentially advantageous method for treating tumors. Globally, institutions have progressed in registered clinical trials of BNCT for multiple body parts. This review summarized the current achievements in registered clinical trials, Investigator-initiated clinical trials, aimed to integrate the latest clinical research literature on BNCT and to shed light on future study directions.

PubMed

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Development example of internal exposure calculation system in medium-sized radiation facilities Reviewed

IMADA Yui, ISOBE Midori, NAGAMATSU Tomohiro, TERATO Hiroaki, HANAFUSA Tadashi

Japanese Journal of Radiation Safety Management 23 ( 2 ) 78 - 82 2024

Authorship：Corresponding author Language：Japanese Publisher：Japanese Society of Radiation Safety Management

When calculating internal exposure dose, a method of extracting and evaluating representatives is recommended. We have developed an evaluation system that calculates internal doses using records of radioisotopes use and radiation workers’ entry into controlled areas. By using this system, it is possible to evaluate internal doses based on correct working hours and to evaluate internal doses of non-representatives, thereby improving the accuracy of radiation safety management.

DOI： 10.11269/jjrsm.23.78

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Particle and Heavy Ion Transport Code System‐Based Microdosimetry for the Development of Boron Agents for Boron Neutron Capture Therapy Reviewed

Takafumi Shigehira, Tadashi Hanafusa, Kazuyo Igawa, Tomonari Kasai, Shuichi Furuya, Hisakazu Nishimori, Yoshinobu Maeda, Hiroyuki Michiue, Atsushi Fujimura

Advanced Theory and Simulations 2023.4

Practical Peport of the Group-based Management That Restricts Simultaneous Use of Radioisotopes Reviewed

Yui Imada, Midori Isobe, Tomohiro Nagamatsu, Hiroaki Terato, Tadashi Hanafusa

Japanese Journal of Radiation Safety Management 21 ( 2 ) 64 - 68 2022.11

In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy Reviewed

4. Atsushi Fujimura, Seiji Yasui, Kazuyo Igawa, Ai Ueda, Kaori Watanabe, Tadashi Hanafusa, Yasuaki Ichikawa, Sachiko Yoshihashi, Kazuki Tsuchida, Atsunori Kamiya and Shuichi Furuya

Cells 9 ( 10 ) 2149 - 2149 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer appears to be a suitable target for BPA-BNCT, because the expression levels of L-type amino acid transporter 1 (LAT1), one of the amino acid transporters responsible for BPA uptake, are elevated in most cases of H&N cancer. However, in other types of cancer including malignant brain tumors, LAT1 is not always highly expressed. To expand the possibility of BNCT for these cases, we previously developed poly-arginine peptide (polyR)-conjugated mercaptoundecahydrododecaborate (BSH). PolyR confers the cell membrane permeability and tumor selectivity of BSH. However, the molecular determinants for the properties are not fully understood. In this present study, we have identified the cluster of differentiation 44 (CD44) protein and translational machinery proteins as a major cell surface target and intracellular targets of BSH-polyR, respectively. CD44, also known as a stem cell-associated maker in various types of cancer, is required for the cellular uptake of polyR-conjugated molecules. We showed that BSH-polyR was predominantly delivered to a CD44High cell population of cancer cells. Once delivered, BSH-polyR interacted with the translational machinery components, including the initiation factors, termination factors, and poly(A)-biding protein (PABP). As a proof of principle, we performed BSH-polyR-based BNCT against glioma stem-like cells and revealed that BSH-polyR successfully induced BNCT-dependent cell death specifically in CD44High cells. Bioinformatics analysis indicated that BSH-polyR would be suitable for certain types of malignant tumors. Our results shed light on the biochemical properties of BSH-polyR, which may further contribute to the therapeutic optimization of BSH-BNCT in the future.

DOI： 10.3390/cells9102149

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The accelerator-based boron neutron capture reaction evaluation system for head and neck cancer Reviewed

Shou Wang, Kazuyo Igawa, Ryo Ogawara, Mitsuru Suda, Tsuyoshi Hamano, Soichiro Ibaragi, Tadashi Hanafusa, Yasuaki Ichikawa, Akira Sasakia.

Applied Radiation and Isotopes 165 2020.7

Radiocesium concentration in stems, leaves, and panicles of rice grown in a sandy soil replacement paddy field treated with different rates of cattle manure compost in Kawamata, Fukushima Reviewed

3. Nittaya WAKAI, Morihiro MAEDA, Toshiro ONO, Tadashi HANAFUSA, Jun YAMASHITA and Kuniyuki SAITOH

Journal of Environmental Science for Sustainable Society (JESSS) 2019 ( 9 ) 1 - 10 2019.7

Factors affecting 137Cs concentration in wild plants and soils of different land use in Iitate village after the Fukushima nuclear power plant accident. Reviewed

4. Nittaya WAKAI, Jun YAMASHITA, Takashi ENOMOTO, Tadashi HANAFUSA, Toshiro ONO, Morihiro MAEDA

Radiation Safety Management 2018.9

In vitro analysis of radioprotective effect of monoterpenes Reviewed

Ken-ichi Kudo, Tadashi Hanafusa, Toshiro Ono

JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY 313 ( 1 ) 169 - 174 2017.7

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Monoterpenes are naturally occurring hydrocarbons composed of two units of isoprenes. They exhibit antioxidant activity to scavenge reactive oxygen species, such as hydroxyl radicals. We investigated the potential of monoterpenes such as thymol, linalool, and menthol to act as radioprotectants. The proliferation of EL4 cells, a mouse lymphoma cell line, treated with linalool at a concentration of 500 mu M or more was not affected by X-ray irradiation. Plasmid-nicking assay performed using formamidopyrimidine-DNA glycosylase showed that linalool prevented single strand breaks and oxidized purines on pUC19 plasmid DNA. These findings indicate that linalool has the ability to scavenge reactive oxygen species and is a potential radioprotector.

DOI： 10.1007/s10967-017-5268-0

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Oncogenic function of the homeobox A13-long noncoding RNA HOTTIP-insulin growth factor-binding protein 3 axis in human gastric cancer Reviewed

Sophie S. W. Wang, Kenly Wuputra, Chung-Jung Liu, Yin-Chu Lin, Yi-Ting Chen, Chee-Yin Chai, Chen-Lung Steve Lin, Kung-Kai Kuo, Ming-Ho Tsai, Shin-Wei Wang, Ker-Kong Chen, Hiroyuki Miyoshi, Yukio Nakamura, Shigeo Saito, Tadashi Hanafusa, Deng-Chyang Wu, Chang-Shen Lin, Kazunari K. Yokoyama

ONCOTARGET 7 ( 24 ) 36049 - 36064 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：IMPACT JOURNALS LLC

To study the mechanisms of gastric tumorigenesis, we have established CSN cell line from human normal gastric mucosa, and CS12, a tumorigenic and invasive gastric cancer cell line from CSN passages. Many stem cell markers were expressed in both CSN and CS12 cells, but LGR5 and NANOG were expressed only in CS12 cells. Increased expression of homeobox A13 (HoxA13) and its downstream cascades was significant for the tumorigenic activity of CS12 cells, and was associated with recruitment of E2F-1 to HoxA13 promoter accompanied with increased trimethylation of histone H3 lysine 4 (H3K4me3) at the hypomethylated E2F motifs. Knockdown of HoxA13 caused the downregulation of long non-coding RNA HOTTIP and insulin growth factor-binding protein 3 (IGFBP-3) genes, indicating that both were targets of HoxA13. Concurrent regulation of HoxA13-HOTTIP was mediated by the mixed lineage leukemia-WD repeat domain 5 complex, which caused the trimethylation of H3K4 and then stimulated cell proliferation. HoxA13 transactivated the IGFBP-3 promoter through the HOX-binding site. Activation of IGFBP-3 stimulated the oncogenic potential and invasion activity. Increased expression of HoxA13 (63.2%) and IGFBP-3 (28.6%) was detected in human gastric cancer tissues and was found in the gastric cancer data of The Cancer Genome Atlas. Taken together, the HoxA13 HOTTIP IGFBP-3 cascade is critical for the carcinogenic characteristics of CS12 cells.

DOI： 10.18632/oncotarget.9102

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Adsorption and removal of strontium in aqueous solution by synthetic hydroxyapatite Reviewed

Yuichi Nishiyama, Tadashi Hanafusa, Jun Yamashita, Yoko Yamamoto, Toshiro Ono

JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY 307 ( 2 ) 1279 - 1285 2016.2

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Hydroxyapatite (HAP) is a main mineral constituent of bone and tooth and has an outstanding bio-compatibility. HAP is a possible sorbent for heavy metals in wastewater due to its high adsorption capacity and low water solubility. We developed a removal system of Sr-90 from aqueous solution by HAP column procedure. More than 90 % of Sr-90 was adsorbed and removed from the Sr-90 containing solution. Divalent cations, Ca2+, had little effect on the removal of Sr-90 up to a concentration of 1 mmol L-1. This clearly indicates that the HAP column technique is advantageous with respect to the capacity to adsorb Sr-90 from water present in the environment.

DOI： 10.1007/s10967-015-4228-9

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An Evaluation of Radiation Exposure and Contamination in PET Facility Reviewed

Hidekazu SAKUNO, Keiko YAMATO, Tadashi HANAFUSA, Toshiro ONO

Japanese Journal of Radiation Safety Management 14 ( 2 ) 91 - 95 2015

A simple method for sampling and measurement of radiocarbon by a passive diffusion sampling technique Radiation Reviewed

Tomohiro NAGAMATSU, Tadashi HANAFUSA, Toshiro ONO

Radiation Safety Management 14 ( 1 ) 9 - 14 2015

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Society of Radiation Safety Management

Passive diffusion sampling has been widely used to monitor organic and inorganic pollutants in the environment. We herein developed a new and simple passive diffusion sampling method to monitor ¹⁴C in the indoor working environment of radioisotope facilities. The badge-type Shikata sampler is an open-end type with no diffusion cap that fits a collection filter with a diameter of 25 mm. This sampler could efficiently collect indoor ¹⁴C with good reliability and a collection efficiency that was 10-fold higher than that of the conventional active pumped method. The Shikata sampler is small, simple, and easy to handle. It may be subsidiary used to monitor indoor ¹⁴C concentrations in radioisotope working rooms, in which radioactivity must be measured once a month as recommended by the Industrial Safety and Health Law.<br>

DOI： 10.12950/rsm.14.9

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Other Link： http://search.jamas.or.jp/link/ui/2016061476

Estimation of soil-to-plant transfer factors of radiocesium in 99 wild plant species grown in arable lands 1 year after the Fukushima 1 Nuclear Power Plant accident Reviewed

Jun Yamashita, Takashi Enomoto, Masao Yamada, Toshiro Ono, Tadashi Hanafusa, Tomohiro Nagamatsu, Shoji Sonoda, Yoko Yamamoto

JOURNAL OF PLANT RESEARCH 127 ( 1 ) 11 - 22 2014.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

One year after the deposition of radionuclides from the Fukushima 1 Nuclear Power Plant (A formal name is Fukushima Daiichi Nuclear Power Station) in March 2011, radiocesium (Cs-134, Cs-137) concentrations ([Cs]) were comprehensively investigated in the wild plants of 99 species most of which were annual or summer green perennial herbs and started to grow from April 2012 at the heavily contaminated fields of paddy (three study sites) and upland (one study site) in Fukushima Prefecture. The survey was conducted three times (April, July and October) in the year. In each site, soils (soil cores of 5-cm depth) and plants (aerial shoots) were collected for determination of [Cs] on a dry weight basis, and then the transfer factor (TF) of radiocesium from soil to plant ([Cs](plant)/[Cs](soil)) was estimated in each species. The [Cs] values of both soils and plants largely varied. However, some species exhibited relatively high TF values (more than 0.4) (e.g., Athyrium yokoscense, Dryopteris tokyoensis, and Cyperus brevifolius), while others exhibited almost negligible values (less than 0.01) (e.g., Salix miyabeana, Humulus scandens, and Elymus tsukushiensis). In addition, judging from the 11 species grown in both paddy and upland fields, TF values were generally higher in the paddy fields. The estimation of phytoextraction efficiency of soil radiocesium by weed communities in the paddy fields suggests that the weed community is not a practical candidate for phytoremediation technique.

DOI： 10.1007/s10265-013-0605-z

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Practice of the safe handling of radioisotopes using naturally occurring radioactive materials Reviewed

HANAFUSA Tadashi, NAGAMATSU Tomohiro, ONO Toshiro

Japanese Journal of Radiation Safety Management 13 ( 2 ) 166 - 172 2014

Authorship：Lead author Language：Japanese Publisher：Japanese Society of Radiation Safety Management

We proposed a practical protocol for the safe handling of radiation and radioisotopes using the naturally occurring radioactive materials (NORMs) ⁸⁷Rb and ⁴⁰K. The protocol can be utilized for the education and training course for radiation handling workers. Rubidium chloride solutions were used for the practice of dilution of unsealed radioisotopes instead of ³²P. Rubidium chloride and potassium chloride solid radiation sources were used for the practice of monitoring of the surface contamination using the GM survey meter instead of ³²P and ¹⁴C. Rubidium chloride solutions were also used for the practice of the contamination check by the smear method. Substitution of the radioisotopes under the Laws Concerning the Prevention from Radiation Hazards due to Radioisotope and others to NORMs can be successfully achieved without notable demerits. We supposed that most of the practice for the safe handling of radioisotopes could be carried out outside a controlled area.<br>

DOI： 10.11269/jjrsm.13.166

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Other Link： https://jlc.jst.go.jp/DN/JALC/10041555346?from=CiNii

A purification system for 64Cu produced by a biomedical cyclotron for antibody PET imaging Reviewed

Teruaki Toyota, Tadashi Hanafusa, Takashi Oda, Iwane Koumura, Takanori Sasaki, Eiji Matsuura, Hiromi Kumon, Tsuneo Yano, Toshiro Ono

Journal of Radioanalytical and Nuclear Chemistry 298 ( 1 ) 295 - 300 2013

Language：English Publishing type：Research paper (scientific journal)

Ion exchange is a simple and efficient method for separating no-carrier-added 64Cu from an irradiated Ni target. We developed a semi-automated two-round 64Cu separation system equipped with a strong-base anion exchange resin column. We first verified the efficiency of the system using a non-radioactive substitute consisting of 25 mg of Ni and 127 ng of Cu, and confirmed that Cu was completely eluted at the second round of the separation step. After the bombardment, separation of 64Cu from the Ni target was achieved with high radiochemical purity. 64Cu produced and separated in this study had an extremely low level of Ni impurity. It could be used for labeling monoclonal antibodies for antibody positron emission tomography imaging and synthesizing radiopharmaceuticals. © 2012 The Author(s).

DOI： 10.1007/s10967-012-2340-7

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Serological identification of Tektin5 as a cancer/testis antigen and its immunogenicity Reviewed

Tadashi Hanafusa, Ali Eldib Ali Mohamed, Shohei Domae, Eiichi Nakayama, Toshiro Ono

BMC CANCER 12 ( 1 ) 520 2012.11

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Identification of new cancer antigens is necessary for the efficient diagnosis and immunotherapy. A variety of tumor antigens have been identified by several methodologies. Among those antigens, cancer/testis (CT) antigens have became promising targets.
Methods: The serological identification of antigens by the recombinant expression cloning (SEREX) methodology has been successfully used for the identification of cancer/testis (CT) antigens. We performed the SEREX analysis of colon cancer.
Results: We isolated a total of 60 positive cDNA clones comprising 38 different genes. They included 2 genes with testis-specific expression profiles in the UniGene database, such as TEKT5 and a CT-like gene, A kinase anchoring protein 3 (AKAP3). Quantitative real-time RT-PCR analysis showed that the expression of TEKT5 was restricted to the testis in normal adult tissues. In malignant tissues, TEKT5 was aberrantly expressed in a variety of cancers, including colon cancer. A serological survey of 101 cancer patients with different cancers by ELISA revealed antibodies to TEKT5 in 13 patients, including colon cancer. None of the 16 healthy donor serum samples were reactive in the same test.
Conclusion: We identified candidate new CT antigen of colon cancer, TEKT5. The findings indicate that TEKT5 is immunogenic in humans, and suggest its potential use as diagnostic as well as an immunotherapeutic reagent for cancer patients.

DOI： 10.1186/1471-2407-12-520

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Isolation and characterization of human lung cancer antigens by serological screening with autologous antibodies Reviewed

Tadashi Hanafusa, Ali Eldib Ali Mohamed, Kenta Kitaoka, Yoshihiro Ohue, Eiichi Nakayama, Toshiro Ono

CANCER LETTERS 301 ( 1 ) 57 - 62 2011.2

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Serological analysis of a recombinant cDNA expression library (SEREX) derived from two lung adenocarcinoma cancer cell lines using autologous sera led to the isolation of 41 positive cDNA clones comprising 28 different antigens. They coded for a variety of nuclear and cytoplasmic proteins. Among the antigens, nucleoporin 107 (NUP107) was isolated most frequently (5 of 41 clones). The second most frequently isolated antigen was coded for by C21orf58 (4 of 41 clones). During serological analysis of selected antigens based on their reactivity to sera from normal individuals and lung cancer patients, none of the antigens showed a cancer-restricted recognition pattern. However, five genes including NUP107 showed higher expression when we examined the changes in gene expression in five different adenocarcinoma cell lines, including those used in SEREX, compared with their levels in normal lung tissues by cDNA microarray analysis. On the other hand, the expression levels of five genes including C21orf58 were down regulated in all adenocarcinoma cell lines. This SEREX study combining comprehensive gene expression assays has added to the growing list of lung cancer antigens, which may aid the development of diagnostic and immunotherapeutic reagents for patients with lung cancer. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.canlet.2010.10.024

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Proposal of a Utilization of a Luminous Bacterium in the Teaching and Learning of Radiation Safety Reviewed

Tadashi Hanafusa, Akihiro Sakoda, Tomohiro Nagamatsu, Ikuo Kinno, Toshiro Ono

Radiation Safety Management 10 ( 1 ) 8 - 13 2011

An Assessment of Radioactivity Level in 51Cr-contaminated Dry Solid Waste Generated from a Research Facility for Verification of Clearance Levels Reviewed

Tomohiro Nagamatsu, Tadashi Hanafusa, Toshiro Ono, Kiyonori Yamaoka.

Radiation Safety Management 9 ( 1 ) 7 - 12 2010

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Society of Radiation Safety Management

Radioactive waste generated from research laboratories and other facilities is regulated by the Law Concerning Prevention from Radiation Hazards due to Radioisotopes etc. (Prevention Law). However, the Prevention Law does not provide the level of clearance or the procedures to follow for compliance monitoring. To assess radioactivity amounts for making decisions about clearance levels, the radioactivity levels in dry solid semi-combustible wastes generated from biomedical research, such as ⁵¹Cr-release assays, were measured and evaluated. Radioactivity of semi-combustible waste was 1.42-6.32% of the initial level. In comparison, records for the past 8 years in the Shikata Laboratory, Department of Radiation Research, Okayama University Advanced Science Research Center, indicated 7% to 90% of the initial radioactivity remained in the waste and was differed widely among researchers. This study determined an accurate radioactivity level in dry solid waste, which could lead to savings in disposal costs.<br>

DOI： 10.12950/rsm.9.7

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