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Yasui Hironobu

Faculty of Veterinary Medicine Veterinary Medicine Applied Veterinary SciencesProfessor

Researcher basic information

■ Degree
  • Doctor of Philosophy, Hokkaido University
■ URL
researchmap URLホームページURL■ Various IDs
Researcher number
  • 10570228
ORCID IDResearcher ID
  • E-3794-2010
J-Global ID■ Research Keywords and Fields
Research Keyword
  • Ferroptosis
  • Senescence
  • 核医学
  • イメージング
  • 放射線生物学
  • 低酸素
  • 放射線腫瘍学
Research Field
  • Environmental Science/Agriculture Science, Chemical substance influence on environment
  • Environmental Science/Agriculture Science, Radiation influence
  • Life Science, Veterinary medical science
  • Life Science, Radiological sciences
■ Educational Organization

Career

■ Career
Career
  • Apr. 2025 - Present
    Hokkaido University, Laboratory of Radiation Biology, Department of Applied Veterinary Sciences, Graduate School of Veterinary Medicine, Professor
  • Jul. 2018 - Mar. 2025
    Hokkaido University, Laboratory of Radiation Biology Department of Applied Veterinary Sciences Graduate School of Veterinary Medicine, Associate Professor
  • Apr. 2016 - Jun. 2018
    Hokkaido University, Central Institute of Isotope Science, Associate Professor
  • Sep. 2009 - Mar. 2016
    Hokkaido University, Laboratory of Radiation Biology Department of Environmental Veterinary Sciences Graduate School of Veterinary Medicine, Assistant Professor
  • Mar. 2012 - Aug. 2012
    National Cancer Institute / National Institutes of Health, Visiting Fellow
  • Sep. 2008 - Aug. 2009
    National Cancer Institute / National Institutes of Health, Postdoctoral Fellow
  • Apr. 2007 - Aug. 2008
    日本学術振興会, 日本学術振興会特別研究員
Educational Background
  • Apr. 2004 - Mar. 2008, Hokkaido University, 獣医学研究科, 獣医学専攻, Japan
  • Apr. 1998 - Mar. 2004, Hokkaido University, School of Veterinary Medicine, Veterinary Medicine, Japan
  • Apr. 1997 - Mar. 1998, Osaka University, School of Science, Department of Physics
Committee Memberships
  • Apr. 2026 - Present
    日本アイソトープ協会, 放射線安全取扱部会 北海道支部委員, Society
  • Apr. 2026 - Present
    Japanese Journal of Veterinary Research, Editor in Chief
  • Sep. 2025 - Present
    日本放射線腫瘍学会生物部会, 常任幹事, Society
  • May 2024 - Present
    日本酸化ストレス学会, 理事, Society
  • Apr. 2024 - Present
    International Association for the Sensitization of Cancer Treatment, director, Society
  • Sep. 2023 - Present
    日本放射線腫瘍学会生物部会, 幹事, Society
  • Aug. 2023 - Present
    日本獣医学会, 評議委員, Society
  • Jul. 2023 - Present
    Journal of Clinical Biochemistry and Nutrition, Editor
  • Jul. 2022 - Present
    Journal of Radiation Research, Managing Editor
  • May 2022 - Present
    日本酸化ストレス学会, 代議員, Society
  • Jun. 2020 - Present
    日本放射線影響学会, 学術評議員, Society
  • Jul. 2018 - Present
    Japanese Journal of Veterinary Research, Editor
  • Apr. 2015 - Present
    電子スピンサイエンス学会, 電子スピンサイエンス編集委員, Society
  • Jun. 2018 - May 2026
    泊発電所環境保全監視協議会委員, Autonomy
  • Apr. 2025 - Mar. 2026
    Japanese Journal of Veterinary Research, Associate Editor
  • Apr. 2022 - Mar. 2026
    日本放射線影響学会, 論文紹介企画小委員会委員長, Society
  • Apr. 2020 - Mar. 2026
    日本アイソトープ協会, 放射線安全取扱部会 企画専門委員, Society
  • Feb. 2024 - Jan. 2026
    電子スピンサイエンス学会, 電子スピンサイエンス編集委員長, Society
  • Feb. 2020 - Nov. 2023
    日本酸化ストレス学会, 若手の会 会長, Society
  • Jan. 2017 - Dec. 2017
    若手放射線生物学研究会, 運営委員, Society
  • Jan. 2015 - Dec. 2016
    若手放射線生物学研究会, 副運営委員, Society
  • Jan. 2013 - Dec. 2013
    若手放射線生物学研究会, 運営委員, Society

Research activity information

■ Awards
  • May 2024, 日本酸化ストレス学会, 日本酸化ストレス学会学術賞
    安井博宣
  • Jul. 2023, International Association for the Sensitization of Cancer Treatment, Association Award of International Association for the Sensitization of Cancer Treatment
    Hironobu Yasui
  • Jun. 2021, 日本放射線腫瘍学会生物部会, 生物部会賞
    安井博宣
  • Oct. 2017, 日本放射線影響学会, 日本放射線影響学会奨励賞
    安井 博宣
  • Nov. 2015, 電子スピンサイエンス学会, 電子スピンサイエンス学会奨励賞
    安井 博宣
  • Sep. 2015, 日本放射線影響学会, 放射線ワークショップ優秀発表賞
    安井 博宣
  • Mar. 2014, Informa Healthcare Young Investigator Award 2014
    安井 博宣
  • Feb. 2012, 19th JSPS Core-to-Core Seminar Winter School Young Investigator Award
    YASUI Hironobu
  • Nov. 2010, 第49回電子スピンサイエンス学会年会若手優秀発表賞
    安井博宣, Japan
■ Papers
  • Advances in redox imaging for cancer diagnosis and therapy.
    Hironobu Yasui; Kazuhiro Kato; Tomoki Bo; Osamu Inanami
    Journal of clinical biochemistry and nutrition, 78, 1, 14, 18, Jan. 2026, [Peer-reviewed], [Invited], [Lead author, Corresponding author], [Domestic magazines]
    English, Scientific journal, Cancer remains a leading cause of global morbidity and mortality, necessitating continuous innovations in diagnosis and therapy. Redox biology, the balance between reactive oxygen species production and antioxidant defenses, plays a central role in tumor initiation, progression, and therapeutic response. Elevated reactive oxygen species levels drive DNA damage, genomic instability, and tumor-promoting signaling, whereas adaptive antioxidant responses promote survival, therapeutic resistance, and recurrence. Chemotherapy and radiotherapy partly exert their cytotoxic effects through reactive oxygen species generation. However, tumors with enhanced redox-buffering capacity often evade reactive oxygen species-mediated killing. Ferroptosis, iron-dependent cell death driven by lipid peroxidation, is a key redox-linked pathway that synergizes with radiotherapy, offering new radiosensitization strategies. Redox imaging is a non-invasive approach to map oxidative and reductive dynamics in tumors. This review outlines the unique strengths of advancements, including optical imaging with redox-sensitive probes, positron emission tomography tracers targeting glutamine metabolism or system Xc -, magnetic resonance imaging with nitroxide-based probes and dynamic nuclear polarization, and electron paramagnetic resonance imaging. Together, these developments underscore the potential of redox imaging as a research and clinical tool. By enabling functional tumor characterization, patient stratification, and treatment monitoring, redox-based imaging provides a framework for precision oncology and development of redox-modulating therapies.
  • Non-invasive electron paramagnetic resonance imaging detects tumor redox imbalance induced by ferroptosis.
    Kazuhiro Kato; Hironobu Yasui; Hideo Sato-Akaba; Miho C Emoto; Hirotada G Fujii; Maciej M Kmiec; Periannan Kuppusamy; Masaki Nagane; Tadashi Yamashita; Osamu Inanami
    Redox report : communications in free radical research, 30, 1, 2454887, 2454887, Dec. 2025, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Targeting ferroptosis, cell death caused by the iron-dependent accumulation of lipid peroxides, and disruption of the redox balance are promising strategies in cancer therapy owing to the physiological characteristics of cancer cells. However, the detection of ferroptosis using in vivo imaging remains challenging. We previously reported that redox maps showing the reduction power per unit time of implanted tumor tissues via non-invasive redox imaging using a novel, compact, and portable electron paramagnetic resonance imaging (EPRI) device could be compared with tumor tissue sections. This study aimed to apply the EPRI technique to the in vivo detection of ferroptosis. Notably, redox maps reflecting changes in the redox status of tumors induced by the ferroptosis-inducing agent imidazole ketone erastin (IKE) were compared with the immunohistochemical images of 4-hydroxynonenal (4-HNE) in tumor tissue sections. Our comparison revealed a negative correlation between the reducing power of tumor tissue and the number of 4-HNE-positive cells. Furthermore, the control and IKE-treated groups exhibited significantly different distributions on the correlation map. Therefore, redox imaging using EPRI may contribute to the non-invasive detection of ferroptosis in vivo.
  • Synthesis and preclinical evaluation of a 68Ga-labeled peptide for PET imaging of transferrin receptor 1 in tumor.
    Longxin Lin; Yuki Mizuno; Yuki Shibata; Hironobu Yasui; Yuji Kuge
    European journal of nuclear medicine and molecular imaging, 08 Aug. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: Transferrin receptor 1 (TfR1) is a transmembrane glycoprotein that mediates cellular iron uptake. Despite its potential as a target for tumor diagnosis, the lack of suitable TfR1 ligands has hindered the development of effective TfR1 imaging agents. We labeled a recently discovered TfR1 ligand, TfRB1G3, with Ga-68 and evaluated its potential for TfR1 imaging through preclinical experiments. METHODS: TfRB1G3 was modified with HBED-CC and radiolabeled with 67/68Ga ([67/68Ga]Ga-TfRB1G3). Human glioblastoma (U87MG) cells were transfected with TfR1-targeting siRNA (TfR1-knockdown) or non-targeting siRNA (control), and accumulation of [67Ga]Ga-TfRB1G3 was evaluated. The KD value of [67Ga]Ga-TfRB1G3 for TfR1 was also calculated. Ex vivo biodistribution was conducted in normal and U87MG tumor-bearing mice after injecting [67Ga]Ga-TfRB1G3. PET imaging studies were conducted after injecting [68Ga]Ga-TfRB1G3, with/without co-injection of 10 nmol TfRB1G3 in mice bearing U87MG tumors. RESULTS: [67/68Ga]Ga-TfRB1G3 was obtained with high radiochemical purity (> 90%). The accumulation of [67Ga]Ga-TfRB1G3 in the TfR1-knockdown cells (22.0 ± 1.1% Dose/mg) was significantly lower than that in the control (308.5 ± 14.3% Dose/mg). The KD value was 1.0 nM. Tumor accumulation of [67Ga]Ga-TfRB1G3 was higher than in any other organs except the kidneys, and co-injection of TfRB1G3 significantly reduced the tumor accumulation by more than 90%. PET imaging with [68Ga]Ga-TfRB1G3 clearly visualized TfR1-positive tumor as early as 20 min post-injection. CONCLUSION: [68Ga]Ga-TfRB1G3 demonstrated excellent affinity and specificity for TfR1 both in vitro and in vivo, providing clear PET images of TfR1-positive tumors shortly after injection. [68Ga]Ga-TfRB1G3 would enable sensitive and quantitative imaging of TfR1 expression.
  • Glutathione-associated redox regulation alleviates radio-resistance of canine cancer stem-like cells with low proteasome activity.
    Koangyong Sung; Kenji Hosoya; Tatsuya Deguchi; Koya Yamashita; Sangho Kim; Takafumi Sunaga; Hironobu Yasui; Osamu Inanami; Masahiro Okumura
    Scientific reports, 15, 1, 18017, 18017, 23 May 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Radio-resistance of cancer stem-like cells (CSCs) is associated with the failure of radiation therapy. ZsGreen1-positive (ZsG⁺) cells, which exhibit low proteasome activity, have been used to enable the detection and isolation of CSCs. However, the mechanisms of radio-resistance in canine tumor cells with low proteasome activity remain unclear. This study aimed to elucidate the radio-resistance mechanisms of ZsG+ cells by identifying a potential target of canine CSCs. ZsG+ cells, isolated using flow cytometric cell sorting, were compared with ZsG- cells. Sulfasalazine was used to suppress glutathione (GSH) synthesis by inhibiting xCT. In vitro experiments demonstrated a significantly higher radio-resistance in ZsG+ cells than in ZsG- cells. After X-irradiation, ZsG+ cells had fewer p53‑binding protein 1 (53BP1) foci, low reactive oxygen species (ROS) accumulation, and high GSH content. Sulfasalazine caused radiosensitization of ZsG+ cells with an increased number of 53BP1 foci by decreasing GSH contents and increasing ROS accumulation. The low proteasome activity played a role in xCT upregulation. In conclusion, canine tumor cells with low proteasome activity are radio-resistant due to high GSH content and low ROS accumulation. Sulfasalazine causes radiosensitization of the tumor cells by altering redox balance by inhibiting GSH synthesis for effective targeting of canine CSCs.
  • Enhancement of radio-sensitivity by inhibition of Janus kinase signaling with oclacitinib in canine tumor cell lines.
    Ryo Owaki; Kenji Hosoya; Tatsuya Deguchi; Satoru Konnai; Naoya Maekawa; Tomohiro Okagawa; Hironobu Yasui; Sangho Kim; Takafumi Sunaga; Masahiro Okumura
    Molecular therapy. Oncology, 33, 1, 200946, 200946, 20 Mar. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, A combination of irradiation and oclacitinib, a Janus kinase (JAK) inhibitor used in dogs, could lead to synergistic anticancer effects in canine tumors. However, the anti-tumor effects of oclacitinib remain unclear. This study investigated the radio-sensitizing effect of oclacitinib in canine tumors and determined its underlying mechanisms using osteosarcoma (HMPOS), malignant melanoma (CMeC), and thyroid adenocarcinoma (CTAC) cell lines. A clonogenic assay and a tumor growth assessment in a xenograft mouse model (BALB/cAJcl-nu/nu) were performed to evaluate the radio-sensitizing effects of oclacitinib. Oclacitinib enhanced the radio-sensitivity of tumor cells both in vitro and in vivo. The signal transducer and activator of transcription (STAT)3 expression was activated and suppressed by oclacitinib in X-irradiation-exposed cells. Oclacitinib enhanced radiation-induced apoptosis only in HMPOS cells by inhibiting anti-apoptotic genes. In addition, oclacitinib inhibited the transcription of cell-cycle-regulating genes and arrested cell cycle progression from the G1 phase to subsequent phases. In conclusion, oclacitinib enhanced radio-sensitivity both in vitro and in vivo by triggering apoptosis and impeding cell cycle progression via STAT3 inhibition in canine tumor cell lines. This study suggested the clinical therapeutic potential of oclacitinib and radiation therapy in enhancing treatment efficacy and outcomes in canine tumors.
  • Hypoxia-induced increase in sphingomyelin synthase 2 aggravates ischemic skeletal muscle inflammation.
    Hinano Mizugaki; Masaki Nagane; Hideo Sato-Akaba; Maciej Kmiec; Periannan Kuppusamy; Hironobu Yasui; Osamu Inanami; Hironobu Murakami; Naoyuki Aihara; Junichi Kamiie; Wataru Mizunoya; Ibuki Yasuda; Tomoki Fukuyama; Yuko Naya; Tadashi Yamashita
    The FEBS journal, 292, 5, 1086, 1105, Mar. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Critical limb ischemia (CLI) is the most advanced stage of peripheral arterial disease, posing a high risk of mortality. Sphingomyelin, a sphingolipid synthesized by sphingomyelin synthases (SMSs) 1 and 2, plays an essential role in signal transduction as a component of lipid rafts. However, the role of sphingomyelin in the inflammation of ischemic skeletal muscles remains unclear. In this study, we analyzed the roles of sphingomyelin and SMSs in CLI-induced myopathy using a mouse hindlimb ischemia model. We observed that hypoxia after CLI triggered an increase in SMS2 levels, thereby elevating sphingomyelin concentrations in ischemic skeletal muscles. The expression of SMS2 and sphingomyelin was induced by hypoxia in C2C12 myotubes and regulated by the prolyl hydroxylase domain enzyme. Additionally, SMS2 deficiency suppressed skeletal muscle inflammation after CLI, attenuated the phosphorylation of inhibitor of κBα (IκBα), and reduced the nuclear translocation of nuclear factor κB (NFκB) p65. Meanwhile, the administration of sphingomyelin hampered skeletal muscle inflammation by inhibiting IκBα phosphorylation and NFκB p65 nuclear translocation and extending inflammation post-CLI. Our results suggest that hypoxia-induced enhancement in SMS2 levels and the consequent increase in sphingomyelin expression levels promote inflammation in ischemic muscle tissues via the NFκB pathway and propose sphingomyelin as a potential therapeutic target in patients with CLI and other hypoxia-related inflammatory diseases.
  • Thymidine Phosphorylase Imaging Probe for Differential Diagnosis of Metabolic dysfunction-associated Steatohepatitis.
    Kei Higashikawa; Riho Uehara; Sawako Horiguchi; Yuki Shibata; Naoto Okubo; Yuki Mizuno; Hironobu Yasui; Shunsuke Ohnishi; Hiroshi Takeda; Yuji Kuge
    Molecular imaging and biology, 26, 6, 1036, 1045, 13 Nov. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises simple steatosis (SS), which has a low risk of mortality, and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to liver cirrhosis and hepatocellular carcinoma. Because differentiation between MASH and SS is the most important issue in the diagnosis of MASLD, the establishment of noninvasive diagnostic methods is urgently needed. In this study, we evaluated the potential of [123I]IIMU, a thymidine phosphorylase (TYMP) targeted SPECT imaging probe, for differential diagnosis of MASLD in a preclinical animal model. PROCEDURES: SS and MASH mice were prepared by feeding db/db mice with a standard diet and a methionine/choline-deficient diet, respectively. Control mice were prepared by feeding m/m mice with a standard diet. TYMP expression in the liver was evaluated by RT-PCR, western blotting, and immunohistochemistry. The biodistribution of [125I]IIMU in the three model mice was evaluated at 30 min post-injection. SPECT/CT imaging studies of the three model mice were performed 30 min after injection of [123I]IIMU. RESULTS: Hepatic TYMP expression level was the highest in the SS mice and the lowest in the MASH mice at both mRNA and protein levels. The immunohistochemistry experiment showed a patchy distribution of TYMP only in the liver of MASH mice. In the biodistribution study, the hepatic accumulation of [125I]IIMU was the highest in the SS mice and the lowest in the MASH mice. The SPECT/CT imaging study showed similar results to the biodistribution experiment. CONCLUSION: Hepatic TYMP expression level may serve as a promising imaging biomarker for differential diagnosis of SS and MASH. SPECT imaging using [123I]IIMU potentially provides a novel noninvasive diagnostic method to differentiate MASH and SS.
  • USP2 Mitigates Reactive Oxygen Species-Induced Mitochondrial Damage via UCP2 Expression in Myoblasts.
    Hiroshi Kitamura; Masaki Fujimoto; Mayuko Hashimoto; Hironobu Yasui; Osamu Inanami
    International journal of molecular sciences, 25, 22, 06 Nov. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Ubiquitin-specific protease 2 (USP2) maintains mitochondrial integrity in culture myoblasts. In this study, we investigated the molecular mechanisms underlying the protective role of USP2 in mitochondria. The knockout (KO) of the Usp2 gene or the chemical inhibition of USP2 induced a robust accumulation of mitochondrial reactive oxygen species (ROS), accompanied by defects in mitochondrial membrane potential, in C2C12 myoblasts. ROS removal by N-acetyl-L-cysteine restored the mitochondrial dysfunction induced by USP2 deficiency. Comprehensive RT-qPCR screening and following protein analysis indicated that both the genetic and chemical inhibition of USP2 elicited a decrease in uncoupling protein 2 (UCP2) at mRNA and protein levels. Accordingly, the introduction of a Ucp2-expressing construct effectively recovered the mitochondrial membrane potential, entailing an increment in the intracellular ATP level in Usp2KO C2C12 cells. In contrast, USP2 deficiency also decreased peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) protein in C2C12 cells, while it upregulated Ppargc1a mRNA. Overexpression studies indicated that USP2 potentially stabilizes PGC1α in an isopeptidase-dependent manner. Given that PGC1α is an inducer of UCP2 in C2C12 cells, USP2 might ameliorate mitochondrial ROS by maintaining the PGC1α-UCP2 axis in myoblasts.
  • Mechanism of the Radioresistant Colorectal Cancer Cell Line SW480RR Established after Fractionated X Irradiation.
    Koya Yamashita; Hironobu Yasui; Tomoki Bo; Masaki Fujimoto; Osamu Inanami
    Radiation research, 202, 1, 38, 50, 23 May 2024, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Radioresistant cancer cells are risk factors for recurrence and are occasionally detected in recurrent tumors after radiotherapy. Intratumor heterogeneity is believed to be a potential cause of treatment resistance. Heterogeneity in DNA content has also been reported in human colorectal cancer; however, little is known about how such heterogeneity changes with radiotherapy or how it affects cancer radioresistance. In the present study, we established radioresistant clone SW480RR cells after fractionated X-ray irradiation of human colorectal cancer-derived SW480.hu cells, which are composed of two cell populations with different chromosome numbers, and examined how cellular radioresistance changed with fractionated radiotherapy. Compared with the parental cell population, which mostly comprised cells with higher ploidy, the radioresistant clones showed lower ploidy and less initial DNA damage. The lower ploidy cells in the parental cell population were identified as having radioresistance prior to irradiation; thus, SW480RR cells were considered intrinsically radioresistant cells selected from the parental population through fractionated irradiation. This study presents a practical example of the emergence of radioresistant cells from a cell population with ploidy heterogeneity after irradiation. The most likely mechanism is the selection of an intrinsically radioresistant population after fractionated X-ray irradiation, with a background in which lower ploidy cells exhibit lower initial DNA damage.
  • Feasibility study of multimodal imaging for redox status and glucose metabolism in tumor.
    Kazuhiro Kato; Hironobu Yasui; Hideo Sato-Akaba; Miho C Emoto; Hirotada G Fujii; Maciej M Kmiec; Periannan Kuppusamy; Yuki Mizuno; Yuji Kuge; Masaki Nagane; Tadashi Yamashita; Osamu Inanami
    Free radical biology & medicine, 218, 57, 67, 02 Apr. 2024, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Understanding the tumor redox status is important for efficient cancer treatment. Here, we noninvasively detected changes in the redox environment of tumors before and after cancer treatment in the same individuals using a novel compact and portable electron paramagnetic resonance imaging (EPRI) device and compared the results with glycolytic information obtained through autoradiography using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). Human colon cancer HCT116 xenografts were used in the mice. We used 3-carbamoyl-PROXYL (3CP) as a paramagnetic and redox status probe for the EPRI of tumors. The first EPRI was followed by the intraperitoneal administration of buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, or X-ray irradiation of the tumor. A second EPRI was performed on the following day. Autoradiography was performed after the second EPRI. After imaging, the tumor sections were evaluated by histological analysis and the amount of reducing substances in the tumor was measured. BSO treatment and X-ray irradiation significantly decreased the rate of 3CP reduction in tumors. Redox maps of tumors obtained from EPRI can be compared with tissue sections of approximately the same cross section. BSO treatment reduced glutathione levels in tumors, whereas X-ray irradiation did not alter the levels of any of the reducing substances. Comparison of the redox map with the autoradiography of [18F]FDG revealed that regions with high reducing power in the tumor were active in glucose metabolism; however, this correlation disappeared after X-ray irradiation. These results suggest that the novel compact and portable EPRI device is suitable for multimodal imaging, which can be used to study tumor redox status and therapeutic efficacy in cancer, and for combined analysis with other imaging modalities.
  • Application of copper (I) selective ligands for PET imaging of reactive oxygen species through metabolic trapping
    Tetsuro Tada; Yuki Mizuno; Yuki Shibata; Hironobu Yasui; Yuji Kuge
    Nuclear Medicine and Biology, 134-135, 108914, 108914, Elsevier BV, Apr. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, INTRODUCTION: Reactive oxygen species (ROS) are attractive targets for clinical PET imaging. In this study, we hypothesized that PET imaging of ROS would be possible by using chelating ligands (L) that form stable complexes with copper (I) but not with copper (II), based on metabolic trapping. Namely, when [64Cu][CuI(L)2]+ is oxidized by ROS, the oxidized complex will release [64Cu]Cu2+. Then, the released [64Cu]Cu2+ will be trapped inside the cell, resulting in PET signal depending on the redox potential of ROS. To examine the potential of this novel molecular design for ROS imaging, we synthesized copper (I) complexes with bicinchoninic acid (BCA) disodium salt and bathocuproinedisulfonic acid (BCS) disodium salt and evaluated their reactivity with several kinds of ROS. In addition, the cellular uptake of [64Cu][CuI(BCS)2]3- and the stability of [64Cu][CuI(BCS)2]3- in a biological condition were also evaluated. METHODS: [64Cu]Cu2+ was reduced to [64Cu]Cu+ by ascorbic acid and coordinated with BCA and BCS in the acetate buffer to synthesize [64Cu][CuI(BCA)2]3- and [64Cu][CuI(BCS)2]3-. The radiochemical yields were determined by thin-layer chromatography (TLC). After [64Cu][CuI(BCS)2]3- was incubated with hydroxyl radical, lipid peroxide, superoxide, and hydrogen peroxide, the percentage of released [64Cu]Cu2+ from the parent complex was evaluated by TLC. HT-1080 human fibrosarcoma cells were treated with 0.1 % Dimethyl sulfoxide (control), imidazole ketone erastin (IKE), or IKE + ferrostatin-1 (Fer-1). Then, the uptake of [64Cu][CuI(BCS)2]3- to HT-1080 cells in each group was evaluated as %Dose/mg protein. Lastly, [64Cu][CuI(BCS)2]3- was incubated in human plasma, and its intact ratio was determined by TLC. RESULTS: The radiochemical yield of [64Cu][CuI(BCS)2]3- (86 ± 1 %) was higher than that of [64Cu][CuI(BCA)2]3- (44 ± 3 %). [64Cu][CuI(BCA)2]3- was unstable and partially decomposed on TLC. After [64Cu][CuI(BCS)2]3- was reacted with hydroxyl radical, lipid peroxide, and superoxide, 67 ± 2 %, 44 ± 13 %, and 22 ± 3 % of total radioactivity was detected as [64Cu]Cu2+, respectively. On the other hand, the reaction with hydrogen peroxide did not significantly increase the ratio of [64Cu]Cu2+ (4 ± 1 %). These results suggest that [64Cu][CuI(BCS)2]3- could be used for detecting high-redox-potential ROS such as hydroxyl radical and lipid peroxide with high selectivity. The cellular uptake values of [64Cu][CuI(BCS)2]3- in the control, IKE, and Fer-1 group were 42 ± 2, 54 ± 2, and 47 ± 5 %Dose/mg protein (n = 3), respectively, suggesting the ROS specific uptake of [64Cu][CuI(BCS)2]3-. On the other hand, the intact ratio after the incubation of [64Cu][CuI(BCS)2]3- in human plasma was 9 ± 5 %. CONCLUSION: PET imaging of ROS would be possible by using a copper (I) selective ligand, based on metabolic trapping. Although improvement of the membrane permeability and the stability of copper (I) complexes is required, the present results pave the way for the development of novel 64Cu-labeled complexes for PET imaging of ROS.
  • In vivo imaging of acute physiological responses after treatment of cancer with near-infrared photoimmunotherapy.
    Kohei Nakajima; Akiyo Sugikawa; Hironobu Yasui; Kei Higashikawa; Chie Suzuki; Takahiro Natsume; Motofumi Suzuki; Hideo Takakura; Mayu Tomita; Sachi Takahashi; Kenji Hirata; Yasuhiro Magata; Yuji Kuge; Mikako Ogawa
    Molecular imaging and biology, 25, 4, 648, 658, Springer Science and Business Media LLC, Aug. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer phototherapy using an antibody-photosensitizer conjugate (Ab-IR700). By NIR light irradiation, Ab-IR700 forms a water-insoluble aggregation on the plasma membrane of cancer cells, leading to lethal membrane damage of cancer cells with high selectivity. However, IR700 produces singlet oxygen, which induces non-selective inflammatory responses such as edema in normal tissues around the tumor. Understanding such treatment-emergent responses is important to minimize side effects and improve clinical outcomes. Thus, in this study, we evaluated physiological responses during NIR-PIT by magnetic resonance imaging (MRI) and positron emission tomography (PET). PROCEDURES: Ab-IR700 was intravenously injected into tumor-bearing mice with two tumors on the right and left sides of the dorsum. At 24 h after injection, a tumor was irradiated with NIR light. Edema formation was examined by T1/T2/diffusion-weighted MRI and inflammation was investigated by PET with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). Because inflammation can increase vascular permeability via inflammatory mediators, we evaluated changes in oxygen levels in tumors using a hypoxia imaging probe, [18F]fluoromisonidazole ([18F]FMISO). RESULTS: The uptake of [18F]FDG in the irradiated tumor was significantly decreased compared to the control tumor, indicating the impairment of glucose metabolism induced by NIR-PIT. MRI and [18F]FDG-PET images showed that inflammatory edema with [18F]FDG accumulation was present in the surrounding normal tissues of the irradiated tumor. Furthermore, [18F]FMISO accumulation in the center of the irradiated tumor was relatively low, indicating the enhancement of oxygen supply due to increased vascular permeability. In contrast, high [18F]FMISO accumulation was observed in the peripheral region, indicating enhancement of hypoxia in the region. This could be because inflammatory edema was formed in the surrounding normal tissues, which blocked blood flow to the tumor. CONCLUSIONS: We successfully monitored inflammatory edema and changes in oxygen levels during NIR-PIT. Our findings on the acute physiological responses after light irradiation will help to develop effective measures to minimize the side effects in NIR-PIT.
  • Electron Paramagnetic Resonance Implemented with Multiple Harmonic Detections Successfully Maps Extracellular pH In Vivo.
    Ririko Nakaoka; Kazuhiro Kato; Kumiko Yamamoto; Hironobu Yasui; Shingo Matsumoto; Igor A Kirilyuk; Valery V Khramtsov; Osamu Inanami; Hiroshi Hirata
    Analytical chemistry, 95, 8, 3940, 3950, American Chemical Society (ACS), 28 Feb. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Extracellular acidification indicates a metabolic shift in cancer cells and is, along with tissue hypoxia, a hallmark of tumor malignancy. Thus, non-invasive mapping of extracellular pH (pHe) is essential for researchers to understand the tumor microenvironment and to monitor tumor response to metabolism-targeting drugs. While electron paramagnetic resonance (EPR) has been successfully used to map pHe in mouse xenograft models, this method is not sensitive enough to map pHe with a moderate amount of exogenous pH-sensitive probes. Here, we show that a modified EPR system achieves twofold higher sensitivity by using the multiple harmonic detection (MHD) method and improves the robustness of pHe mapping in mouse xenograft models. Our results demonstrate that treatment of a mouse xenograft model of human-derived pancreatic ductal adenocarcinoma cells with the carbonic anhydrase IX (CAIX) inhibitor U-104 delays tumor growth with a concurrent tendency toward further extracellular acidification. We anticipate that EPR-based pHe mapping can be expanded to monitor the response of other metabolism-targeting drugs. Furthermore, pHe monitoring can also be used for the development of improved metabolism-targeting cancer treatments.
  • Intracerebral Transplantation of Mesenchymal Stromal Cell Compounded with Recombinant Peptide Scaffold against Chronic Intracerebral Hemorrhage Model.
    Soichiro Takamiya; Masahito Kawabori; Tsukasa Kitahashi; Kentaro Nakamura; Yuki Mizuno; Hironobu Yasui; Yuji Kuge; Aki Tanimori; Yasuyuki Takamatsu; Kohei Yuyama; Hideo Shichinohe; Miki Fujimura
    Stem cells international, 2022, 8521922, 8521922, Hindawi Limited, 31 Jul. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Background. Due to the lack of effective therapies, stem cell transplantation is an anticipated treatment for chronic intracerebral hemorrhage (ICH), and higher cell survival and engraftment are considered to be the key for recovery. Mesenchymal stromal cells (MSCs) compounded with recombinant human collagen type I scaffolds (CellSaics) have a higher potential for cell survival and engraftment compared with solo-MSCs, and we investigated the validity of intracerebral transplantation of CellSaic in a chronic ICH model. Methods. Rat CellSaics (rCellSaics) were produced by rat bone marrow-derived MSC (rBMSCs). The secretion potential of neurotrophic factors and the cell proliferation rate were compared under oxygen-glucose deprivation (OGD) conditions. rCellSaics, rBMSCs, or saline were transplanted into the hollow cavity of a rat chronic ICH model. Functional and histological analyses were evaluated, and single-photon emission computed tomography for benzodiazepine receptors was performed to monitor sequential changes in neuronal integrity. Furthermore, human CellSaics (hCellSaics) were transplanted into a chronic ICH model in immunodeficient rats. Antibodies neutralizing brain-derived neurotrophic factor (BDNF) were used to elucidate its mode of action. Results. rCellSaics demonstrated a higher secretion potential of trophic factors and showed better cell proliferation in the OGD condition. Animals receiving rCellSaics displayed better neurological recovery, higher intracerebral BDNF, and better cell engraftment; they also showed a tendency for less brain atrophy and higher benzodiazepine receptor preservation. hCellSaics also promoted significant functional recovery, which was reversed by BDNF neutralization. Conclusion. Intracerebral transplantation of CellSaics enabled neurological recovery in a chronic ICH model and may be a good option for clinical application.
  • Continuous monitoring of post-irradiation reoxygenation and cycling hypoxia using electron paramagnetic resonance imaging.
    Tatsuya Kawai; Masayuki Matsuo; Yoichi Takakusagi; Keita Saito; Fuminori Hyodo; Nallathamby Devasahayam; Shingo Matsumoto; Shun Kishimoto; Hironobu Yasui; Kazutoshi Yamamoto; Murali C Krishna
    NMR in biomedicine, 35, 10, e4783, 03 Jun. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Reoxygenation has a significant impact on the tumor response to radiotherapy. With the developments in radiotherapy technology, the relevance of the reoxygenation phenomenon in treatment efficacy has been a topic of interest. Evaluating the reoxygenation in the tumor microenvironment throughout the course of radiation therapy is important in developing effective treatment strategies. PURPOSE: In the present study, we used electron paramagnetic resonance imaging (EPRI) to directly map and quantify the partial oxygen pressure (pO2 ) in tumor tissues. MATERIALS AND METHODS: Human colorectal cancer cell lines, HT29 and HCT116, were used to induce tumor growth in female athymic nude mice. Tumors were irradiated with 3, 10, or 20 Gy using an X-ray irradiator. Prior to each EPRI scan, magnetic resonance imaging (MRI) was performed to obtain T2-weighted anatomical images for reference. The differences in the mean pO2 were determined through two-tailed Student's t-test and one-way analysis of variance (ANOVA). RESULTS: The median pO2 60 min after irradiation was found to be lower in HCT116 than in HT29 (9.1 ± 1.5 vs. 14.0 ± 1.0 mmHg, P = 0.045). There was a tendency for delayed and incomplete recovery of pO2 in the HT29 tumor when a higher dose of irradiation (10 and 20 Gy) was applied. Moreover, there was a dose-dependent increase in the hypoxic areas (pO2 < 10 mmHg) 2 h and 24 h after irradiation in all groups. In addition, an area that showed pO2 fluctuation between hypoxia and normoxia (pO2 > 10 mmHg) was also identified surrounding the region with stable hypoxia, and it slightly enlarged after recovery from acute hypoxia. CONCLUSION: We demonstrated the reoxygenation phenomenon in an in vivo xenograft model study using EPRI. These findings might lead to new knowledge of the reoxygenation process and possibilities of a new radiation therapy concept, namely, reoxygenation-based radiation therapy.
  • Preclinical studies for improving radiosensitivity of non-small cell lung cancer cell lines by combining glutaminase inhibition and senolysis.
    Masaki Fujimoto; Ritsuko Higashiyama; Hironobu Yasui; Koya Yamashita; Osamu Inanami
    Translational oncology, 21, 101431, 101431, 19 Apr. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Glutamine metabolism, known as glutaminolysis, is abnormally activated in many cancer cells with KRAS or BRAF mutations or active c-MYC. Glutaminolysis plays an important role in the proliferation of cancer cells with oncogenic mutations. In this study, we characterized radiation-induced cell death, which was enhanced by glutaminolysis inhibition in non-small cell lung cancer A549 and H460 cell lines with KRAS mutation. A clonogenic survival assay revealed that treatment with a glutaminase inhibitor, CB839, enhanced radiosensitivity. X-irradiation increased glutamate production, mitochondrial oxygen consumption, and ATP production, whereas CB839 treatment suppressed these effects. The data suggest that the enhancement of glutaminolysis-dependent energy metabolism for ATP production is important for survival after X-irradiation. Evaluation of the cell death phenotype revealed that glutaminolysis inhibitory treatment with CB839 or a low-glutamine medium significantly promoted the proliferation of β-galactosidase-positive and IL-6/IL-8 secretory cells among X-irradiated tumor cells, corresponding to an increase in the senescent cell population. Furthermore, treatment with ABT263, a Bcl-2 family inhibitor, transformed senescent cells into apoptotic cells. The findings suggest that combination treatment with a glutaminolysis inhibitor and a senolytic drug is useful for efficient radiotherapy.
  • Eribulin improves tumor oxygenation demonstrated by 18F-DiFA hypoxia imaging, leading to radio-sensitization in human cancer xenograft models.
    Tomoki Bo; Hironobu Yasui; Tohru Shiga; Yuki Shibata; Masaki Fujimoto; Motofumi Suzuki; Kei Higashikawa; Naoki Miyamoto; Osamu Inanami; Yuji Kuge
    European journal of nuclear medicine and molecular imaging, 49, 3, 821, 833, (一社)日本放射線影響学会, Feb. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, PURPOSE: Eribulin, an inhibitor of microtubule dynamics, is known to show antitumor effects through its remodeling activity in the tumor vasculature. However, the extent to which the improvement of tumor hypoxia by eribulin affects radio-sensitivity remains unclear. We utilized 1-(2,2-dihydroxymethyl-3-18F-fluoropropyl)-2-nitroimidazole (18F-DiFA), a new PET probe for hypoxia, to investigate the effects of eribulin on tumor hypoxia and evaluate the radio-sensitivity during eribulin treatment. METHODS: Mice bearing human breast cancer MDA-MB-231 cells or human lung cancer NCI-H1975 cells were administered a single dose of eribulin. After administration, mice were injected with 18F-DiFA and pimonidazole, and tumor hypoxia regions were analyzed. For the group that received combined treatment with radiation, 18F-DiFA PET/CT imaging was performed before tumors were locally X-irradiated. Tumor size was measured every other day after irradiation. RESULTS: Eribulin significantly reduced 18F-DiFA accumulation levels in a dose-dependent manner. Furthermore, the reduction in 18F-DiFA accumulation levels by eribulin was most significant 7 days after treatment. These results were also supported by reduction of the pimonidazole-positive hypoxic region. The combined treatment showed significant retardation of tumor growth in comparison with the control, radiation-alone, and drug-alone groups. Importantly, tumor growth after irradiation was inversely correlated with 18F-DiFA accumulation. CONCLUSION: These results demonstrated that 18F-DiFA PET/CT clearly detected eribulin-induced tumor oxygenation and that eribulin efficiently enhanced the antitumor activity of radiation by improving tumor oxygenation.
  • Metformin preferentially enhances the radio-sensitivity of cancer stem-like cells with highly mitochondrial respiration ability in HMPOS.
    Tatsuya Deguchi; Kenji Hosoya; Shango Kim; Yusuke Murase; Kumiko Yamamoto; Tomoki Bo; Hironobu Yasui; Osamu Inanami; Mahiro Okumura
    Molecular therapy oncolytics, 22, 143, 151, 24 Sep. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Metformin has many anti-cancer effects, alone or in combination with radiation. However, the mechanism underlying its radio-sensitized effect is still unclear, especially for cancer stem-like cells (CSCs). Here, the radio-sensitized effect of metformin was investigated, and its mechanism was revealed in CSCs derived from canine osteosarcoma cell line (HMPOS), a canine osteosarcoma cell line. Spheroid cells (SCs) were used as CSCs-rich cells derived from sphere formation, and SCs were compared with normal adherent culture cells (ACs). The radio-sensitizing effect of metformin using clonogenic assay and tumor growth in mice xenograft model were evaluated, and the mechanism of its radio-sensitization focusing on mitochondrial function was revealed. Metformin significantly enhanced radio-sensitivity of SCs through its inhibition of the mitochondrial function, as shown by decreased oxygen consumption, decreased mitochondrial membrane potential, and decreased ATP production. Additionally, SCs had a higher ability of mitochondrial respiration than ACs, which may have caused difference of their sensitivity of metformin and irradiation. In conclusion, mitochondrial function might play an important role in the sensitivity of metformin and irradiation, and drugs that target mitochondrial respiration, such as metformin, are promising radio-sensitizers to target CSCs.
  • LAT1 inhibitor JPH203 sensitizes cancer cells to radiation by enhancing radiation-induced cellular senescence.
    Tomoki Bo; Sho Kobayashi; Osamu Inanami; Junichi Fujii; Osamu Nakajima; Tsunekata Ito; Hironobu Yasui
    Translational oncology, 14, 11, 101212, 101212, 27 Aug. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, L-type amino acid transporter 1 (LAT1) is important for transporting neutral amino acids into cells. LAT1 expression is correlated with cancer malignancy, suggesting that LAT1 is a promising target for cancer therapy. JPH203, a potential novel drug targeting LAT1, has been shown to suppress tumor growth in various cancer cell lines. However, a combination study of JPH203 and radiation therapy has not been reported. Here, we examined the effects of JPH203 on radiosensitivity after irradiation in A549 and MIA Paca-2 cells. We showed that X-irradiation increased cellular neutral amino acid uptake via LAT1 in both cell lines. JPH203 inhibited the radiation-induced increase in neutral amino acid uptake. We demonstrated that JPH203, at minimally toxic concentrations, significantly sensitized cancer cells to radiation. JPH203 significantly downregulated mTOR activity and enhanced cellular senescence post-irradiation without reducing ATP and GSH levels. These results indicate that LAT1 inhibition by JPH203 sensitizes cancer cells to radiation by enhancing cellular senescence via mTOR downregulation. Thus, JPH203 may be a potent anti-cancer drug in combination with radiation therapy.
  • KDM2B promotes cell viability by enhancing DNA damage response in canine hemangiosarcoma.
    Kevin Christian Montecillo Gulay; Keisuke Aoshima; Yuki Shibata; Hironobu Yasui; Qin Yan; Atsushi Kobayashi; Takashi Kimura
    Journal of genetics and genomics = Yi chuan xue bao, 48, 7, 618, 630, 20 Jul. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Epigenetic regulators have been implicated in tumorigenesis of many types of cancer; however, their roles in endothelial cell cancers such as canine hemangiosarcoma (HSA) have not been studied. In this study, we find that lysine-specific demethylase 2b (KDM2B) is highly expressed in HSA cell lines compared with normal canine endothelial cells. Silencing of KDM2B in HSA cells results in increased cell death in vitro compared with the scramble control by inducing apoptosis through the inactivation of the DNA repair pathways and accumulation of DNA damage. Similarly, doxycycline-induced KDM2B silencing in tumor xenografts results in decreased tumor sizes compared with the control. Furthermore, KDM2B is also highly expressed in clinical cases of HSA. We hypothesize that pharmacological KDM2B inhibition can also induce HSA cell death and can be used as an alternative treatment for HSA. We treat HSA cells with GSK-J4, a histone demethylase inhibitor, and find that GSK-J4 treatment also induces apoptosis and cell death. In addition, GSK-J4 treatment decreases tumor size. Therefore, we demonstrate that KDM2B acts as an oncogene in HSA by enhancing the DNA damage response. Moreover, we show that histone demethylase inhibitor GSK-J4 can be used as a therapeutic alternative to doxorubicin for HSA treatment.
  • DNA damage response in vascular endothelial senescence: Implication for radiation-induced cardiovascular diseases.
    Masaki Nagane; Hironobu Yasui; Periannan Kuppusamy; Tadashi Yamashita; Osamu Inanami
    Journal of radiation research, 62, 4, 564, 573, 10 Jul. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, A post-exposure cohort study in Hiroshima and Nagasaki reported that low-dose exposure to radiation heightened the risk of cardiovascular diseases (CVD), such as stroke and myocardial infarction, by 14-18% per Gy. Moreover, the risk of atherosclerosis in the coronary arteries reportedly increases with radiation therapy of the chest, including breast and lung cancer treatment. Cellular senescence of vascular endothelial cells (ECs) is believed to play an important role in radiation-induced CVDs. The molecular mechanism of age-related cellular senescence is believed to involve genomic instability and DNA damage response (DDR); the chronic inflammation associated with senescence causes cardiovascular damage. Therefore, vascular endothelial cell senescence is believed to induce the pathogenesis of CVDs after radiation exposure. The findings of several prior studies have revealed that ionizing radiation (IR) induces cellular senescence as well as cell death in ECs. We have previously reported that DDR activates endothelial nitric oxide (NO) synthase, and NO production promotes endothelial senescence. Endothelial NO synthase (eNOS) is a major isoform expressed in ECs that maintains cardiovascular homeostasis. Therefore, radiation-induced NO production, a component of the DDR in ECs, may be involved in CVDs after radiation exposure. In this article, we describe the pathology of radiation-induced CVD and the unique radio-response to radiation exposure in ECs.
  • Transferrin-based radiolabeled probe predicts the sensitivity of human renal cancer cell lines to ferroptosis inducer erastin.
    Yuki Shibata; Hironobu Yasui; Kei Higashikawa; Yuji Kuge
    Biochemistry and biophysics reports, 26, 100957, 100957, Jul. 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Ferroptosis induction has been recognized as a novel cancer therapeutic strategy. To effectively apply ferroptosis-targeting cancer therapy to individual patients, a diagnostic indicator for selecting this therapeutic strategy from a number of molecular targeting drugs is needed. However, to date, methods that can predict the efficacy of ferroptosis-targeting treatment have not been established yet. In this study, we focused on the iron metabolic pathway to develop a nuclear imaging technique for diagnosing the susceptibility of cancer cells to ferroptosis. As a nuclear probe, human transferrin (Tf) was labeled with Gallium-68 (68Ga) using 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as a chelator (68Ga-NOTA-Tf). Western blot assay and clonogenic survival assay with human renal cancer cell lines A498 and 786-O revealed that the protein expression level of transferrin receptor1 (TfR1) and sensitivity to a ferroptosis inducer, erastin, were correlated. A cellular uptake assay with 68Ga-NOTA-Tf revealed that the cancer cells sensitive to erastin highly internalized the 68Ga-NOTA-Tf. Furthermore, treatment with the TfR1 inhibitor ferristatin II reduced the cellular uptake of 68Ga-NOTA-Tf, indicating that the intracellular uptake of the probe was mediated by TfR1. These results suggest that 68Ga-NOTA-Tf can be useful in predicting the sensitivity of cancer cells to ferroptosis inducers.
  • Redox-sensitive mapping of a mouse tumor model using sparse projection sampling of electron paramagnetic resonance.
    Kota Kimura; Nami Iguchi; Hitomi Nakano; Hironobu Yasui; Shingo Matsumoto; Osamu Inanami; Hiroshi Hirata
    Antioxidants & redox signaling, 36, 1-3, 57, 69, 13 Apr. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, AIMS: This work aimed to establish an accelerated imaging system for redox-sensitive mapping in a mouse tumor model using electron paramagnetic resonance (EPR) and nitroxyl radicals. RESULTS: Sparse sampling of EPR spectral projections was demonstrated for a solution phantom. The reconstructed three-dimensional (3D) images with filtered back-projection (FBP) and compressed sensing (CS) image reconstruction were quantitatively assessed for the solution phantom. Mouse xenograft models of a human-derived pancreatic ductal adenocarcinoma cell line, MIA PaCa-2, were also measured for redox-sensitive mapping with the sparse sampling technique. INNOVATION: A short-lifetime redox-sensitive nitroxyl radical (15N-labeled perdeuterated Tempone) could be measured to map the decay rates of the EPR signals for the mouse xenograft models. Acceleration of 3D EPR image acquisition broadened the choices of nitroxyl radical probes with various redox sensitivities to biological environments. CONCLUSION: Sparse sampling of EPR spectral projections accelerated image acquisition in the 3D redox-sensitive mapping of mouse tumor-bearing legs 4-fold compared to conventional image acquisition with FBP.
  • Inhibition of xanthine oxidase in the acute phase of myocardial infarction prevents skeletal muscle abnormalities and exercise intolerance.
    Hideo Nambu; Shingo Takada; Satoshi Maekawa; Junichi Matsumoto; Naoya Kakutani; Takaaki Furihata; Ryosuke Shirakawa; Takashi Katayama; Takayuki Nakajima; Katsuma Yamanashi; Yoshikuni Obata; Ippei Nakano; Masaya Tsuda; Akimichi Saito; Arata Fukushima; Takashi Yokota; Junko Nio-Kobayashi; Hironobu Yasui; Kei Higashikawa; Yuji Kuge; Toshihisa Anzai; Hisataka Sabe; Shintaro Kinugawa
    Cardiovascular research, 117, 3, 805, 819, 22 Feb. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, AIMS: Exercise intolerance in patients with heart failure (HF) is partly attributed to skeletal muscle abnormalities. We have shown that reactive oxygen species (ROS) play a crucial role in skeletal muscle abnormalities, but the pathogenic mechanism remains unclear. Xanthine oxidase (XO) is reported to be an important mediator of ROS overproduction in ischaemic tissue. Here, we tested the hypothesis that skeletal muscle abnormalities in HF are initially caused by XO-derived ROS and are prevented by the inhibition of their production. METHODS AND RESULTS: Myocardial infarction (MI) was induced in male C57BL/6J mice, which eventually led to HF, and a sham operation was performed in control mice. The time course of XO-derived ROS production in mouse skeletal muscle post-MI was first analysed. XO-derived ROS production was significantly increased in MI mice from Days 1 to 3 post-surgery (acute phase), whereas it did not differ between the MI and sham groups from 7 to 28 days (chronic phase). Second, mice were divided into three groups: sham + vehicle (Sham + Veh), MI + vehicle (MI + Veh), and MI + febuxostat (an XO inhibitor, 5 mg/kg body weight/day; MI + Feb). Febuxostat or vehicle was administered at 1 and 24 h before surgery, and once-daily on Days 1-7 post-surgery. On Day 28 post-surgery, exercise capacity and mitochondrial respiration in skeletal muscle fibres were significantly decreased in MI + Veh compared with Sham + Veh mice. An increase in damaged mitochondria in MI + Veh compared with Sham + Veh mice was also observed. The wet weight and cross-sectional area of slow muscle fibres (higher XO-derived ROS) was reduced via the down-regulation of protein synthesis-associated mTOR-p70S6K signalling in MI + Veh compared with Sham + Veh mice. These impairments were ameliorated in MI + Feb mice, in association with a reduction of XO-derived ROS production, without affecting cardiac function. CONCLUSION: XO inhibition during the acute phase post-MI can prevent skeletal muscle abnormalities and exercise intolerance in mice with HF.
  • Characterization of brown adipose tissue thermogenesis in the naked mole-rat (Heterocephalus glaber), a heterothermic mammal.
    Yuki Oiwa; Kaori Oka; Hironobu Yasui; Kei Higashikawa; Hidemasa Bono; Yoshimi Kawamura; Shingo Miyawaki; Akiyuki Watarai; Takefumi Kikusui; Atsushi Shimizu; Hideyuki Okano; Yuji Kuge; Kazuhiro Kimura; Yuko Okamatsu-Ogura; Kyoko Miura
    Scientific reports, 10, 1, 19488, 19488, 10 Nov. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The naked mole-rat (NMR) is a heterothermic mammal that forms eusocial colonies consisting of one reproductive female (queen), several reproductive males, and subordinates. Despite their heterothermy, NMRs possess brown adipose tissue (BAT), which generally induces thermogenesis in cold and some non-cold environments. Previous studies suggest that NMR-BAT induces thermogenesis by cold exposure. However, detailed NMR-BAT characteristics and whether NMR-BAT thermogenesis occurs in non-cold environments are unknown. Here, we show beta-3 adrenergic receptor (ADRB3)-dependent thermogenic potential of NMR-BAT, which contributes to thermogenesis in the isolated queen in non-cold environments (30 °C). NMR-BAT expressed several brown adipocyte marker genes and showed noradrenaline-dependent thermogenic activity in vitro and in vivo. Although our ADRB3 inhibition experiments revealed that NMR-BAT thermogenesis slightly delays the decrease in body temperature in a cold environment (20 °C), it was insufficient to prevent the decrease in the body temperatures. Even at 30 °C, NMRs are known to prevent the decrease of and maintain their body temperature by heat-sharing behaviors within the colony. However, isolated NMRs maintained their body temperature at the same level as when they are in the colony. Interestingly, we found that queens, but not subordinates, induce BAT thermogenesis in this condition. Our research provides novel insights into NMR thermoregulation.
  • Radiation-induced abnormal centrosome amplification and mitotic catastrophe in human cervical tumor HeLa cells and murine mammary tumor EMT6 cells.
    Masaki Fujimoto; Tomoki Bo; Kumiko Yamamoto; Hironobu Yasui; Tohru Yamamori; Osamu Inanami
    Journal of clinical biochemistry and nutrition, 67, 3, 240, 247, Nov. 2020, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Mitotic catastrophe is a form of cell death linked to aberrant mitosis caused by improper or uncoordinated mitotic progression. Abnormal centrosome amplification and mitotic catastrophe occur simultaneously, and some cells with amplified centrosomes enter aberrant mitosis, but it is not clear whether abnormal centrosome amplification triggers mitotic catastrophe. Here, to investigate whether radiation-induced abnormal centrosome amplification is essential for induction of radiation-induced mitotic catastrophe, centrinone-B, a highly selective inhibitor of polo-like kinase 4, was utilized to inhibit centrosome amplification, since polo-like kinase 4 is an essential kinase in centrosome duplication. When human cervical tumor HeLa cells and murine mammary tumor EMT6 cells were irradiated with 2.5 Gy of X-rays, cells with morphological features of mitotic catastrophe and the number of cells having >2 centrosomes increased in both cell lines. Although centrinone-B significantly inhibited radiation-induced abnormal centrosome amplification in both cell lines, such treatment did not change cell growth and significantly enhanced mitotic catastrophe in HeLa cells exposed to X-rays. In contrast, inhibition of centrosome amplification reduced cell growth and mitotic catastrophe in EMT6 cells exposed to X-rays. These results indicated that the role of radiation-induced abnormal centrosome amplification in radiation-induced mitotic catastrophe changes, depending on the cell type.
  • FTY720 Protects Against Ischemia-Reperfusion Injury by Preventing the Redistribution of Tight Junction Proteins and Decreases Inflammation in the Subacute Phase in an Experimental Stroke Model.
    Zifeng Wang; Kei Higashikawa; Hironobu Yasui; Yuji Kuge; Yusuke Ohno; Akio Kihara; Yenari A Midori; Kiyohiro Houkin; Masahito Kawabori
    Translational stroke research, 11, 5, 1103, 1116, Oct. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Injury due to brain ischemia followed by reperfusion (I/R) may be an important therapeutic target in the era of thrombectomy. FTY720, a widely known sphingosine-1-phosphate receptor agonist, exerts various neuroprotective effects. The aim of this study was to examine the protective effect of FTY720 with respect to I/R injury, especially focusing on blood-brain barrier (BBB) protection and anti-inflammatory effects. Male rats were subjected to transient ischemia and administered vehicle or 0.5 or 1.5 mg/kg of FTY720 immediately before reperfusion. Positron emission tomography (PET) with [18F]DPA-714 was performed 2 and 9 days after the insult to serially monitor neuroinflammation. Bovine and rat brain microvascular endothelial cells (MVECs) were also subjected to oxygen-glucose deprivation (OGD) and reperfusion, and administered FTY720, phosphorylated-FTY720 (FTY720-P), or their inhibitor. FTY720 dose-dependently reduced cell death, the infarct size, cell death including apoptosis, and inflammation. It also ameliorated BBB disruption and neurological deficits compared to in the vehicle group. PET indicated that FTY720 significantly inhibited the worsening of inflammation in later stages. FTY720-P significantly prevented the intracellular redistribution of tight junction proteins but did not increase their mRNA expression. These results suggest that FTY720 can ameliorate I/R injury by protecting the BBB and regulating neuroinflammation.
  • Mitochondrial fission promotes radiation-induced increase in intracellular Ca2+ level leading to mitotic catastrophe in mouse breast cancer EMT6 cells.
    Tomoki Bo; Tohru Yamamori; Kumiko Yamamoto; Masaki Fujimoto; Hironobu Yasui; Osamu Inanami
    Biochemical and biophysical research communications, 522, 1, 144, 150, 29 Jan. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Mitochondrial dynamics are crucial for cellular survival in response to various stresses. Previously, we reported that Drp1 promoted mitochondrial fission after x-irradiation and its inhibition resulted in reduced cellular radiosensitivity and mitotic catastrophe. However, the mechanisms of radiation-induced mitotic catastrophe related to mitochondrial fission remain unclear. In this study, we investigated the involvement of cellular ATP production, ROS generation, and Ca2+ levels in mitotic catastrophe in EMT6 cells. Knockdown of Drp1 and Fis1, which are mitochondrial fission regulators, resulted in elongated mitochondria and significantly attenuated cellular radiosensitivity. Reduced mitochondrial fission mainly decreased mitotic catastrophe rather than necrosis and apoptosis after irradiation. Cellular ATP contents in Drp1 and Fis1 knockdown cells were similar to those in control cells. N-acetylcysteine and 2-glucopyranoside ascorbic acid have no effect on mitotic catastrophe after irradiation. The cellular [Ca2+]i level increased after irradiation, which was completely suppressed by Drp1 and Fis1 inhibition. Furthermore, BAPTA-AM significantly reduced radiation-induced mitotic catastrophe, indicating that cellular Ca2+ is a key mediator of mitotic catastrophe induction after irradiation. These results suggest that mitochondrial fission is associated with radiation-induced mitotic catastrophe via cytosolic Ca2+ regulation.
  • Nucleoside analogs as a radiosensitizer modulating DNA repair, cell cycle checkpoints, and apoptosis.
    Hironobu Yasui; Daisuke Iizuka; Wakako Hiraoka; Mikinori Kuwabara; Akira Matsuda; Osamu Inanami
    Nucleosides, nucleotides & nucleic acids, 39, 1-3, 439, 452, 2020, [Peer-reviewed], [Lead author], [International Magazine]
    English, The combination of low dose of radiation and an anticancer drug is a potent strategy for cancer therapy. Nucleoside analogs are known to have a radiosensitizing effects via the inhibition of DNA damage repair after irradiation. Certain types of nucleoside analogs have the inhibitory effects on RNA synthesis, but not DNA synthesis, with multiple functions in cell cycle modulation and apoptosis. In this review, the most up-to-date findings regarding radiosensitizing nucleoside analogs will be discussed, focusing especially on the mechanisms of action.
  • Preclinical investigation of potential use of thymidine phosphorylase-targeting tracer for diagnosis of nonalcoholic steatohepatitis.
    Kei Higashikawa; Sawako Horiguchi; Makoto Tarisawa; Yuki Shibata; Kazue Ohkura; Hironobu Yasui; Hiroshi Takeda; Yuji Kuge
    Nuclear medicine and biology, 82-83, 25, 32, 16 Dec. 2019, [Peer-reviewed], [International Magazine]
    English, INTRODUCTION: Although liver biopsy is the gold standard for the diagnosis of nonalcoholic steatohepatitis (NASH), it has several problems including high invasiveness and sampling errors. Therefore, the development of alternative methods to overcome these disadvantages is strongly required. In this study, we evaluated the potential use of our tracer targeting thymidine phosphorylase (TYMP), 5-[123I]iodo-6-. CONCLUSIONS: [123I]IIMU may provide a noninvasive means for imaging TYMP expression in the liver and may be applicable to the diagnosis of NASH.
  • High drug efflux pump capacity and low DNA damage response induce doxorubicin resistance in canine hemangiosarcoma cell lines.
    Morita A; Aoshima K; Gulay KCM; Onishi S; Shibata Y; Yasui H; Kobayashi A; Kimura T
    Research in veterinary science, 127, 1, 10, Elsevier BV, Oct. 2019, [Peer-reviewed]
    Scientific journal
  • Biodistribution and radiation dosimetry of the novel hypoxia PET probe [18F]DiFA and comparison with [18F]FMISO.
    Shiro Watanabe; Tohru Shiga; Kenji Hirata; Keiichi Magota; Shozo Okamoto; Takuya Toyonaga; Kei Higashikawa; Hironobu Yasui; Jun Kobayashi; Ken-Ichi Nishijima; Ken Iseki; Hiroki Matsumoto; Yuji Kuge; Nagara Tamaki
    EJNMMI research, 9, 1, 60, 60, 05 Jul. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: To facilitate hypoxia imaging in a clinical setting, we developed 1-(2,2-dihydroxymethyl-3-[18F]-fluoropropyl)-2-nitroimidazole ([18F]DiFA) as a new tracer that targets tumor hypoxia with its lower lipophilicity and efficient radiosynthesis. Here, we evaluated the radiation dosage, biodistribution, human safety, tolerability, and early elimination after the injection of [18F]DiFA in healthy subjects, and we performed a preliminary clinical study of patients with malignant tumors in a comparison with [18F]fluoromisonidazole ([18F]FMISO). RESULTS: The single administration of [18F]DiFA in 8 healthy male adults caused neither adverse events nor abnormal clinical findings. Dynamic and sequential whole-body scans showed that [18F]DiFA was rapidly cleared from all of the organs via the hepatobiliary and urinary systems. The whole-body mean effective dose of [18F]DiFA estimated by using the medical internal radiation dose (MIRD) schema with organ level internal dose assessment/exponential modeling (OLINDA/EXM) computer software 1.1 was 14.4 ± 0.7 μSv/MBq. Among the organs, the urinary bladder received the largest absorbed dose (94.7 ± 13.6 μSv/MBq). The mean absorbed doses of the other organs were equal to or less than those from other hypoxia tracers. The excretion of radioactivity via the urinary system was very rapid, reaching 86.4 ± 7.1% of the administered dose. For the preliminary clinical study, seven patients were subjected to [18F]FMISO and [18F]DiFA positron emission tomography (PET) at 48-h intervals to compare the two tracers' diagnostic ability for tumor hypoxia. The results of the tumor hypoxia evaluation by [18F]DiFA PET at 1 h and 2 h were not significantly different from those obtained with [18F]FMISO PET at 4 h ([18F]DiFA at 1 h, p = 0.32; [18F]DiFA at 2 h, p = 0.08). Moreover, [18F]DiFA PET at both 1 h (k = 0.68) and 2 h (k = 1.00) showed better inter-observer reproducibility than [18F]FMISO PET at 4 h (k = 0.59). CONCLUSION: [18F]DiFA is well tolerated, and its radiation dose is comparable to those of other hypoxia tracers. [18F]DiFA is very rapidly cleared via the urinary system. [18F]DiFA PET generated comparable images to [18F]FMISO PET in hypoxia imaging with shorter waiting time, demonstrating the promising potential of [18F]DiFA PET for hypoxia imaging and for a multicenter trial.
  • Differentiation of bone marrow-derived cells toward thermogenic adipocytes in white adipose tissue induced by the β3 adrenergic stimulation.
    Takeshi Yoneshiro; Woongchul Shin; Ken Machida; Keigo Fukano; Ayumi Tsubota; Yong Chen; Hironobu Yasui; Osamu Inanami; Yuko Okamatsu-Ogura; Kazuhiro Kimura
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33, 4, 5196, 5207, Apr. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Bone marrow provides progenitors of several types of cells, including muscle and white adipocytes, ensuring peripheral tissue homeostasis. However, the role of bone marrow-derived cells (BMCs) in induction of thermogenic adipocytes is unresolved. The purpose of this study is to examine whether BMCs are involved in the emergence of thermogenic adipocytes through adrenergic activation. Irradiation of mice with 8 Gy of X-ray-depleted BMCs and peripheral blood mononucleated cells (PBMCs), which in turn impaired induction of uncoupling protein 1 (UCP1) through administration of β3 adrenergic receptor agonist, CL 316,243 (CL), in inguinal white adipose tissue (iWAT). In contrast, CL-induced UCP1 induction in brown adipose tissue was unaffected by BMC depletion. Transplantation of normal BMCs into mice depleted of BMCs recovered PBMC levels and rescued the ability of iWAT browning by CL. Furthermore, analyses of mice transplanted with green fluorescent protein (GFP)-labeled BMCs revealed that the number of GFP-positive BMCs and PBMCs were significantly decreased by CL and that GFP-positive stromal cells and GFP-positive UCP1-expressing multilocular adipocytes appeared in iWAT after CL administration, demonstrating differentiation of BMC-derived preadipocytes into UCP1-expressing thermogenic adipocytes. These results unveiled a crucial role of the BMC as a nonresident origin for a subset of thermogenic adipocytes, contributing to browning of white adipose tissue.-Yoneshiro, T., Shin, W., Machida, K., Fukano, K., Tsubota, A., Chen, Y., Yasui, H., Inanami, O., Okamatsu-Ogura, Y., Kimura, K. Differentiation of bone marrow-derived cells toward thermogenic adipocytes in white adipose tissue induced by the β3 adrenergic stimulation.
  • A Novel PET Probe "[18F]DiFA" Accumulates in Hypoxic Region via Glutathione Conjugation Following Reductive Metabolism.
    Yoichi Shimizu; Songji Zhao; Hironobu Yasui; Ken-Ichi Nishijima; Hiroki Matsumoto; Tohru Shiga; Nagara Tamaki; Mikako Ogawa; Yuji Kuge
    Molecular imaging and biology, 21, 1, 122, 129, Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: Hypoxia in tumor has close relationship with angiogenesis and tumor progression. Previously, we developed 2,2-dihydroxymethyl-3-[18F]fluoropropyl-2-nitroimidazole ([18F]DiFA) as a novel positron emission tomography (PET) probe for diagnosis of hypoxia. In this study, we elucidated whether the accumulation of [18F]DiFA in cells is dependent on the hypoxic state and revealed how [18F]DiFA accumulates in hypoxic cells in combination with imaging mass spectrometry (IMS). PROCEDURES: FaDu human head and neck cancer cells were treated with [18F]DiFA and then incubated under normoxia (21% O2) or hypoxia (1% O2) for 2 h. The cells were extracted using methanol, and the radioactivities of the precipitates (macromolecule fraction) and supernatants (low-molecular-weight fraction) were measured. FaDu-bearing mice were injected intravenously with [18F]DiFA and with pimonidazole 1 h later. The tumors were excised 2 h after the injection of [18F]DiFA. Autoradiography, IMS, and immunohistochemical (IHC) staining for pimonidazole were performed with serial tumor sections. RESULTS: In the in vitro study, the radioactivity of FaDu cells was significantly higher under hypoxia than that under normoxia (0.53 ± 0.02 vs. 0.27 ± 0.02 %dose/mg protein, p < 0.05). The radioactivity of the low-molecular-weight fraction was 66.3 ± 0.6% in the hypoxic cell. In the in vivo study, [18F]DiFA accumulated in the tumor tissues existed mainly as low-molecular-weight compounds (90.4 ± 0.9%). In addition, the glutathione conjugate of reductive DiFA metabolite (amino-DiFA-GS) existed in tumor tissues revealed by the IMS study, and the distribution pattern of amino-DiFA-GS was very similar to that of the radioactivity and the positive staining area of pimonidazole. CONCLUSIONS: Our results suggest that [18F]DiFA undergoes the glutathione conjugation reaction following reductive metabolism in hypoxic cells, which leads hypoxia-specific PET imaging with [18F]DiFA.
  • The Adjuvant Effect of Squalene, an Active Ingredient of Functional Foods, on Doxorubicin-Treated Allograft Mice.
    Hari Narayan Bhilwade; Naoto Tatewaki; Tetsuya Konishi; Miyako Nishida; Takahiro Eitsuka; Hironobu Yasui; Osamu Inanami; Osamu Handa; Yuji Naito; Nobuo Ikekawa; Hiroshi Nishida
    Nutrition and cancer, 71, 7, 1153, 1164, 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Many functional foods or physiologically active ingredients derived from plants and animals are actively being investigated for their role in chronic disease prevention. Squalene (SQ) is found as active ingredient in the functional foods predominantly present in olive oil and shark liver oil. It is known that during chemotherapy anticancer drugs induce inflammation. SQ has been thought to prevent and suppress inflammation; however, there is little direct evidence available. We examined the adjuvant effect of SQ on tumor-transplanted mice along with anticancer drug doxorubicin (DOX). SQ significantly suppressed the DOX-induced increase in prostaglandin E2 (PGE2) concentration (P < 0.05) in plasma of tumor-bearing mice. SQ inhibited the numbers of writhing response (P < 0.05), formalin-induced pain and decreased COX-2 and substance P expression in the tumor tissue compared to control mice and also enhanced the antitumor efficacy of DOX in allograft mice. Thus, SQ reduces inflammation through modulation of PGE2 production indicating its potential as an adjuvant during chemotherapy in tumor-bearing mice.
  • Erastin, a ferroptosis-inducing agent, sensitized cancer cells to X-ray irradiation via glutathione starvation in vitro and in vivo.
    Shibata Y; Yasui H; Higashikawa K; Miyamoto N; Kuge Y
    PloS one, 14, 12, e0225931, 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, High concentrations of antioxidants in cancer cells are huge obstacle in cancer radiotherapy. Erastin was first discovered as an inducer of iron-dependent cell death called ferroptosis accompanied by antioxidant depletion caused by cystine glutamate antiporter inhibition. Therefore, treatment with erastin is expected to potentially enhance cellular radiosensitivity. In this study, we investigated the influence of treatment with erastin on the radiation efficiency against cancers. The clonogenic ability, glutathione peroxidase 4 (GPX4) expression, and glutathione concentration were evaluated using HeLa and NCI-H1975 adenocarcinoma cell lines treated with erastin and/or X-ray irradiation. For in vivo studies, NCI-H1975 cells were transplanted in the left shoulder of nude mice, and then radiosensitizing effect of erastin and glutathione concentration in the cancer were evaluated. Treatment with erastin induced ferroptosis and decreased the concentration of glutathione and GPX4 protein expression levels in the two tumor cell lines. Moreover, erastin enhanced X-ray irradiation-induced cell death in both human tumor cell lines. Furthermore, erastin treatment of a tumor-transplanted mouse model similarly demonstrated the radiosensitizing effect and decrease in intratumoral glutathione concentration in the in vitro study. In conclusion, our study demonstrated the radiosensitizing effect of erastin on two adenocarcinoma cell lines and the tumor xenograft model accompanied by glutathione depletion, indicating that ferroptosis inducers that reduce glutathione concentration could be applied as a novel cancer therapy in combination with radiotherapy.
  • In Vivo Extracellular pH Mapping of Tumors Using Electron Paramagnetic Resonance.
    Denis A Komarov; Yuki Ichikawa; Kumiko Yamamoto; Neil J Stewart; Shingo Matsumoto; Hironobu Yasui; Igor A Kirilyuk; Valery V Khramtsov; Osamu Inanami; Hiroshi Hirata
    Analytical chemistry, 90, 23, 13938, 13945, 04 Dec. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, An electron paramagnetic resonance (EPR)-based method for noninvasive three-dimensional extracellular pH mapping was developed using a pH-sensitive nitroxyl radical as an exogenous paramagnetic probe. Fast projection scanning with a constant magnetic field sweep enabled the acquisition of four-dimensional (3D spatial +1D spectral) EPR images within 7.5 min. Three-dimensional maps of pH were reconstructed by processing the pH-dependent spectral information on the images. To demonstrate the proposed method of pH mapping, the progress of extracellular acidosis in tumor-bearing mouse legs was studied. Furthermore, extracellular pH mapping was used to visualize the spatial distribution of acidification in different tumor xenograft mouse models of human-derived pancreatic ductal adenocarcinoma cells. The proposed EPR-based pH mapping method enabled quantitative visualization of regional changes in extracellular pH associated with altered tumor metabolism.
  • Anti PD-1 treatment increases [18F]FDG uptake by cancer cells in a mouse B16F10 melanoma model.
    Tomita M; Yasui H; Higashikawa K; Nakajima K; Takakura H; Shiga T; Kuge Y; Ogawa M
    EJNMMI research, 8, 1, 82, Springer Science and Business Media LLC, Aug. 2018, [Peer-reviewed]
    Scientific journal
  • Genotoxic Responses of Mitochondrial Oxygen Consumption Rate and Mitochondrial Semiquinone Radicals in Tumor Cells
    Yamamoto K; Yasui H; Bo T; Yamamori T; Hiraoka W; Yamasaki T; Yamada KI; Inanami O
    Applied Magnetic Resonance, 49, 8, 837, 851, Jul. 2018, [Peer-reviewed], [Invited]
    English, Scientific journal
  • Evaluation of mitochondrial redox status and energy metabolism of X-irradiated HeLa cells by LC/UV, LC/MS/MS and ESR.
    Kumiko Yamamoto; Yoshinori Ikenaka; Takahiro Ichise; Tomoki Bo; Mayumi Ishizuka; Hironobu Yasui; Wakako Hiraoka; Tohru Yamamori; Osamu Inanami
    Free radical research, 52, 6, 648, 660, Jun. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, To evaluate the metabolic responses in tumour cells exposed to ionizing radiation, oxygen consumption rate (OCR), cellular lipid peroxidation, cellular energy status (intracellular nucleotide pool and ATP production), and mitochondrial reactive oxygen species (ROS), semiquinone (SQ), and iron-sulphur (Fe-S) cluster levels were evaluated in human cervical carcinoma HeLa cells at 12 and 24 h after X-irradiation. LC/MS/MS analysis showed that levels of 8-iso PGF2α and 5-iPF2α-VI, lipid peroxidation products of membrane arachidonic acids, were not altered significantly in X-irradiated cells, although mitochondrial ROS levels and OCR significantly increased in the cells at 24 h after irradiation. LC/UV analysis revealed that intracellular AMP, ADP, and ATP levels increased significantly after X-irradiation, but adenylate energy charge (adenylate energy charge (AEC) = [ATP + 0.5 × ADP]/[ATP + ADP + AMP]) remained unchanged after X-irradiation. In low-temperature electron spin resonance (ESR) spectra of HeLa cells, the presence of mitochondrial SQ at g = 2.004 and Fe-S cluster at g = 1.941 was observed and X-irradiation enhanced the signal intensity of SQ but not of the Fe-S cluster. Furthermore, this radiation-induced increase in SQ signal intensity disappeared on treatment with rotenone, which inhibits electron transfer from Fe-S cluster to SQ in complex I. From these results, it was suggested that an increase in OCR and imbalance in SQ and Fe-S cluster levels, which play a critical role in the mitochondrial electron transport chain (ETC), occur after X-irradiation, resulting in an increase in ATP production and ROS leakage from the activated mitochondrial ETC.
  • [18F]DPA-714 PET imaging shows immunomodulatory effect of intravenous administration of bone marrow stromal cells after transient focal ischemia.
    Chengbo Tan; Songji Zhao; Kei Higashikawa; Zifeng Wang; Masahito Kawabori; Takeo Abumiya; Naoki Nakayama; Ken Kazumata; Naoyuki Ukon; Hironobu Yasui; Nagara Tamaki; Yuji Kuge; Hideo Shichinohe; Kiyohiro Houkin
    EJNMMI research, 8, 1, 35, 35, 02 May 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: The potential application of bone marrow stromal cell (BMSC) therapy in stroke has been anticipated due to its immunomodulatory effects. Recently, positron emission tomography (PET) with [18F]DPA-714, a translocator protein (TSPO) ligand, has become available for use as a neural inflammatory indicator. We aimed to evaluate the effects of BMSC administration after transient middle cerebral artery occlusion (MCAO) using [18F]DPA-714 PET. The BMSCs or vehicle were administered intravenously to rat MCAO models at 3 h after the insult. Neurological deficits, body weight, infarct volume, and histology were analyzed. [18F]DPA-714 PET was performed 3 and 10 days after MCAO. RESULTS: Rats had severe neurological deficits and body weight loss after MCAO. Cell administration ameliorated these effects as well as the infarct volume. Although weight loss occurred in the spleen and thymus, cell administration suppressed it. In both vehicle and BMSC groups, [18F]DPA-714 PET showed a high standardized uptake value (SUV) around the ischemic area 3 days after MCAO. Although SUV was increased further 10 days after MCAO in both groups, the increase was inhibited in the BMSC group, significantly. Histological analysis showed that an inflammatory reaction occurred in the lymphoid organs and brain after MCAO, which was suppressed in the BMSC group. CONCLUSIONS: The present results suggest that BMSC therapy could be effective in ischemic stroke due to modulation of systemic inflammatory responses. The [18F]DPA-714 PET/CT system can accurately demonstrate brain inflammation and evaluate the BMSC therapeutic effect in an imaging context. It has great potential for clinical application.
  • Ataxia-Telangiectasia Mutated (ATM) Kinase Regulates eNOS Expression and Modulates Radiosensitivity in Endothelial Cells Exposed to Ionizing Radiation
    Masaki Nagane; M. Lakshmi Kuppusamy; Jennifer An; Jesse M. Mast; Rajan Gogna; Hironobu Yasui; Tohru Yamamori; Osamu Inanami; Periannan Kuppusamy
    Radiation Research, 189, 5, 519, 528, Radiation Research Society, 01 May 2018, [Peer-reviewed]
    English, Scientific journal
  • Preclinical study on hypoxic radiosensitizing effects of glycididazole in comparison with those of doranidazole in vitro and in vivo
    Hironobu Yasui; Nobuo Kubota; Junko Nishizumi; Yuri Sakai; Tohru Yamamori; Osamu Inanami
    Oncology Letters, 15, 2, 1993, 1998, Spandidos Publications, 01 Feb. 2018, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Feasibility of in vivo three-dimensional T-2(*) mapping using dicarboxy-PROXYL and CW-EPR-based single-point imaging
    Harue Kubota; Denis A. Komarov; Hironobu Yasui; Shingo Matsumoto; Osamu Inanami; Igor A. Kirilyuk; Valery V. Khramtsov; Hiroshi Hirata
    MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE, 30, 3, 291, 298, Jun. 2017, [Peer-reviewed]
    English, Scientific journal
  • Analysis of the mechanism of radiation-induced upregulation of mitochondrial abundance in mouse fibroblasts
    Tohru Yamamori; Tomoya Sasagawa; Osamu Ichii; Mie Hiyoshi; Tomoki Bo; Hironobu Yasui; Yasuhiro Kon; Osamu Inanami
    JOURNAL OF RADIATION RESEARCH, 58, 3, 292, 301, May 2017, [Peer-reviewed]
    English, Scientific journal
  • Metabolic analysis of radioresistant medulloblastoma stem-like clones and potential therapeutic targets
    Lue Sun; Takashi Moritake; Kazuya Ito; Yoshitaka Matsumoto; Hironobu Yasui; Hidehiko Nakagawa; Aki Hirayame; Osamu Inanami; Koji Tsuboi
    PLOS ONE, 12, 4, e0176162, Apr. 2017, [Peer-reviewed]
    English, Scientific journal
  • Lipophilic triphenylphosphonium derivatives enhance radiation-induced cell killing via inhibition of mitochondrial energy metabolism in tumor cells
    Hironobu Yasui; Kumiko Yamamoto; Motofumi Suzuki; Yuri Sakai; Tomoki Bo; Masaki Nagane; Eri Nishimura; Tohru Yamamori; Toshihide Yamasaki; Ken-ichi Yamada; Osamu Inanami
    CANCER LETTERS, 390, 160, 167, Apr. 2017, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Attempts of Radiation Dose Measurement in the Teeth of Mice Living around the Nuclear Power Plant in Fukushima Using Electron Spin Resonance Spectroscopy
    Kitaya Taichi; Maeda Teruaki; Yasui Hironobu; Mizukawa Hazuki; Inanami Osamu; Nakata Akifumi; Miura Tomisato; Hosokawa Yoichiro; Kuwabara Mikinori
    Radiation Environment and Medicine, 6, 1, 1, 5, 弘前大学出版会, Feb. 2017, [Peer-reviewed]
    English, Scientific journal
  • Quantitative imaging of pO(2) in orthotopic murine gliomas: hypoxia correlates with resistance to radiation
    Hironobu Yasui; Tatsuya Kawai; Shingo Matsumoto; Keita Saito; Nallathamby Devasahayam; James B. Mitchell; Kevin Camphausen; Osamu Inanami; Murali C. Krishna
    FREE RADICAL RESEARCH, 51, 9-10, 861, 871, 2017, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft
    Naoyuki Ukon; Songji Zhao; Wenwen Yu; Yoichi Shimizu; Ken-ichi Nishijima; Naoki Kubo; Yoshimasa Kitagawa; Nagara Tamaki; Kei Higashikawa; Hironobu Yasui; Yuji Kuge
    EJNMMI RESEARCH, 6, 1, 90, Dec. 2016, [Peer-reviewed]
    English, Scientific journal
  • A Nucleoside Anticancer Drug, 1-(3-C-Ethynyl-beta-D-Ribo-Pentofuranosyl)Cytosine, Induces Depth-Dependent Enhancement of Tumor Cell Death in Spread-Out Bragg Peak (SOBP) of Proton Beam
    Kenichiro Maeda; Hironobu Yasui; Tohru Yamamori; Taeko Matsuura; Seishin Takao; Motofumi Suzuki; Akira Matsuda; Osamu Inanami; Hiroki Shirato
    PLOS ONE, 11, 11, e0166848, Nov. 2016, [Peer-reviewed]
    English, Scientific journal
  • Effect of MPS1 Inhibition on Genotoxic Stress Responses in Murine Tumour Cells
    Motofumi Suzuki; Tohru Yamamori; Hironobu Yasui; Osamu Inanami
    ANTICANCER RESEARCH, 36, 6, 2783, 2792, Jun. 2016, [Peer-reviewed]
    English, Scientific journal
  • Evaluation of the relative biological effectiveness of spot-scanning proton irradiation in vitro
    Kenichiro Maeda; Hironobu Yasui; Taeko Matsuura; Tohru Yamamori; Motofumi Suzuki; Masaki Nagane; Jin-Min Nam; Osamu Inanami; Hiroki Shirato
    JOURNAL OF RADIATION RESEARCH, 57, 3, 307, 311, Jun. 2016, [Peer-reviewed]
    English, Scientific journal
  • Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation
    Tohru Yamamori; Satoshi Ike; Tomoki Bo; Tomoya Sasagawa; Yuri Sakai; Motofumi Suzuki; Kumiko Yamamoto; Masaki Nagane; Hironobu Yasui; Osamu Inanami
    MOLECULAR BIOLOGY OF THE CELL, 26, 25, 4607, 4617, Dec. 2015, [Peer-reviewed]
    English, Scientific journal
  • Roles of ROS and PKC-beta II in ionizing radiation-induced eNOS activation in human vascular endothelial cells
    Kimimasa Sakata; Takashi Kondo; Natsumi Mizuno; Miki Shoji; Hironobu Yasui; Tohru Yamamori; Osamu Inanami; Hiroki Yokoo; Naoki Yoshimura; Yuichi Hattori
    VASCULAR PHARMACOLOGY, 70, 55, 65, Jul. 2015, [Peer-reviewed]
    English, Scientific journal
  • Downregulation of the DNA repair enzyme apurinic/apyrimidinic endonuclease 1 stimulates transforming growth factor-beta 1 production and promotes actin rearrangement
    Yuri Sakai; Tohru Yamamori; Hironobu Yasui; Osamu Inanami
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 461, 1, 35, 41, May 2015, [Peer-reviewed]
    English, Scientific journal
  • Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway
    Masaki Nagane; Hironobu Yasui; Yuri Sakai; Tohru Yamamori; Koichi Niwa; Yuichi Hattori; Takashi Kondo; Osamu Inanami
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 456, 1, 541, 546, Jan. 2015, [Peer-reviewed]
    English, Scientific journal
  • 3-Methyl pyruvate enhances radiosensitivity through increasing mitochondria-derived reactive oxygen species in tumor cell lines
    Naoya Nishida; Hironobu Yasui; Masaki Nagane; Tohru Yamamori; Osamu Inanami
    JOURNAL OF RADIATION RESEARCH, 55, 3, 455, 463, May 2014, [Peer-reviewed]
    English, Scientific journal
  • Radiosensitization of tumor cells through endoplasmic reticulum stress induced by PEGylated nanogel containing gold nanoparticles
    Hironobu Yasui; Ryo Takeuchi; Masaki Nagane; Shunsuke Meike; Yoshinari Nakamura; Tohru Yamamori; Yoshinori Ikenaka; Yasuhiro Kon; Hiroki Murotani; Motoi Oishi; Yukio Nagasaki; Osamu Inanami
    CANCER LETTERS, 347, 1, 151, 158, May 2014, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • In vivo tumour extracellular pH monitoring using electron paramagnetic resonance: the effect of X- ray irradiation
    Jonathan Goodwin; Katsuya Yachi; Masaki Nagane; Hironobu Yasui; Yusuke Miyake; Osamu Inanami; Andrey A. Bobko; Valery V. Khramtsov; Hiroshi Hirata
    NMR IN BIOMEDICINE, 27, 4, 453, 458, Apr. 2014, [Peer-reviewed]
    English, Scientific journal
  • ER stress suppresses DNA double-strand break repair and sensitizes tumor cells to ionizing radiation by stimulating proteasomal degradation of Rad51
    Tohru Yamamori; Shunsuke Meike; Masaki Nagane; Hironobu Yasui; Osamu Inanami
    FEBS LETTERS, 587, 20, 3348, 3353, Oct. 2013, [Peer-reviewed]
    English, Scientific journal
  • Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model
    Masaki Nagane; Hironobu Yasui; Tohru Yamamori; Songji Zhao; Yuji Kuge; Nagara Tamaki; Hiromi Kameya; Hideo Nakamura; Hirotada Fujii; Osamu Inanami
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 437, 3, 420, 425, Aug. 2013, [Peer-reviewed]
    English, Scientific journal
  • EPR Oxygen Imaging and Hyperpolarized C-13 MRI of Pyruvate Metabolism as Noninvasive Biomarkers of Tumor Treatment Response to a Glycolysis Inhibitor 3-Bromopyruvate
    Shingo Matsumoto; Keita Saito; Hironobu Yasui; H. Douglas Morris; Jeeva P. Munasinghe; Martin Lizak; Hellmut Merkle; Jan Henrik Ardenkjaer-Larsen; Rajani Choudhuri; Nallathamby Devasahayam; Sankaran Subramanian; Alan P. Koretsky; James B. Mitchell; Murali C. Krishna
    MAGNETIC RESONANCE IN MEDICINE, 69, 5, 1443, 1450, May 2013, [Peer-reviewed]
    English, Scientific journal
  • The prospective application of a hypoxic radiosensitizer, doranidazole to rat intracranial glioblastoma with blood brain barrier disruption
    Hironobu Yasui; Taketoshi Asanuma; Junichi Kino; Tohru Yamamori; Shunsuke Meike; Masaki Nagane; Nobuo Kubota; Mikinori Kuwabara; Osamu Inanami
    BMC CANCER, 13, 106, Mar. 2013, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Longitudinal Imaging Studies of Tumor Microenvironment in Mice Treated with the mTOR Inhibitor Rapamycin
    Keita Saito; Shingo Matsumoto; Hironobu Yasui; Nallathamby Devasahayam; Sankaran Subramanian; Jeeva P. Munasinghe; Vyomesh Patel; J. Silvio Gutkind; James B. Mitchell; Murali C. Krishna
    PLOS ONE, 7, 11, e49456, Nov. 2012, [Peer-reviewed]
    English, Scientific journal
  • Vincristine enhances amoeboid-like motility via GEF-H1/RhoA/ROCK/Myosin light chain signaling in MKN45 cells
    Masato Eitaki; Tohru Yamamori; Shunsuke Meike; Hironobu Yasui; Osamu Inanami
    BMC CANCER, 12, 469, Oct. 2012, [Peer-reviewed]
    English, Scientific journal
  • Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and mitochondrial content under control of the cell cycle checkpoint
    Tohru Yamamori; Hironobu Yasui; Masayuki Yamazumi; Yusuke Wada; Yoshinari Nakamura; Hideo Nakamura; Osamu Inanami
    FREE RADICAL BIOLOGY AND MEDICINE, 53, 2, 260, 270, Jul. 2012, [Peer-reviewed]
    English, Scientific journal
  • Electron Paramagnetic Resonance Imaging of Tumor pO(2)
    Murali C. Krishna; Shingo Matsumoto; Hironobu Yasui; Keita Saito; Nallathamby Devasahayam; Sankaran Subramanian; James B. Mitchell
    RADIATION RESEARCH, 177, 4, 376, 386, Apr. 2012, [Peer-reviewed]
    English, Scientific journal
  • Antiangiogenic Agent Sunitinib Transiently Increases Tumor Oxygenation and Suppresses Cycling Hypoxia
    Shingo Matsumoto; Sonny Batra; Keita Saito; Hironobu Yasui; Rajani Choudhuri; Chandramouli Gadisetti; Sankaran Subramanian; Nallathamby Devasahayam; Jeeva P. Munasinghe; James B. Mitchell; Murali C. Krishna
    CANCER RESEARCH, 71, 20, 6350, 6359, Oct. 2011, [Peer-reviewed]
    English, Scientific journal
  • 8-Aminoadenosine Enhances Radiation-induced Cell Death in Human Lung Carcinoma A549 Cells
    Shunsuke Meike; Tohru Yamamori; Hironobu Yasui; Masato Eitaki; Akira Matsuda; Osamu Inanami
    JOURNAL OF RADIATION RESEARCH, 52, 4, 456, 463, Jul. 2011, [Peer-reviewed]
    English, Scientific journal
  • A nucleoside anticancer drug, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (TAS106), sensitizes cells to radiation by suppressing BRCA2 expression
    Shunsuke Meike; Tohru Yamamori; Hironobu Yasui; Masato Eitaki; Akira Matsuda; Masami Morimatsu; Masakazu Fukushima; Yasundo Yamasaki; Osamu Inanami
    MOLECULAR CANCER, 10, 92, Jul. 2011, [Peer-reviewed]
    English, Scientific journal
  • Imaging Cycling Tumor Hypoxia
    Shingo Matsumoto; Hironobu Yasui; James B. Mitchell; Murali C. Krishna
    CANCER RESEARCH, 70, 24, 10019, 10023, Dec. 2010, [Peer-reviewed]
    English, Scientific journal
  • Low-Field Magnetic Resonance Imaging to Visualize Chronic and Cycling Hypoxia in Tumor-Bearing Mice
    Hironobu Yasui; Shingo Matsumoto; Nallathamby Devasahayam; Jeeva P. Munasinghe; Rajani Choudhuri; Keita Saito; Sankaran Subramanian; James B. Mitchell; Murali C. Krishna
    CANCER RESEARCH, 70, 16, 6427, 6436, Aug. 2010, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Induction of neurite outgrowth by alpha-phenyl-N-tert-butylnitrone through nitric oxide release and Ras-ERK pathway in PC12 cells
    Hironobu Yasui; Nozomi Ito; Tohru Yamamori; Hideo Nakamura; Jun Okano; Taketoshi Asanuma; Takayuki Nakajima; Mikinori Kuwabara; Osamu Inanami
    FREE RADICAL RESEARCH, 44, 6, 645, 654, Jun. 2010, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • A novel copper(II) coordination at His186 in full-length murine prion protein
    Yasuko Watanabe; Wakako Hiraoka; Manabu Igarashi; Kimihito Ito; Yuhei Shimoyama; Motohiro Horiuchi; Tohru Yamamoria; Hironobu Yasui; Mikinori Kuwabara; Fuyuhiko Inagaki; Osamu Inanami
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 394, 3, 522, 528, Apr. 2010, [Peer-reviewed]
    English, Scientific journal
  • Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI
    Shingo Matsumoto; Hironobu Yasui; Sonny Batra; Yuichi Kinoshita; Marcelino Bernardo; Jeeva P. Munasinghe; Hideo Utsumi; Rajani Choudhuri; Nallathamby Devasahayam; Sankaran Subramanian; James B. Mitchell; Murali C. Krishna
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106, 42, 17898, 17903, Oct. 2009, [Peer-reviewed]
    English, Scientific journal
  • Canine neutrophil dysfunction caused by downregulation of beta 2-integrin expression without mutation
    Saori Kobayashi; Reeko Sato; Yuya Abe; Osamu Inanami; Hironobu Yasui; Katsuhiko Omoe; Jun Yasuda; Careen Hankanga; Shinichi Oda; Juso Sasaki
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 130, 3-4, 187, 196, Aug. 2009, [Peer-reviewed]
    English, Scientific journal
  • Redox regulation in radiation-induced cytochrome c release from mitochondria of human lung carcinoma A549 cells
    Aki Ogura; Shigeru Oowada; Yasuhiro Kon; Aki Hirayama; Hironobu Yasui; Shunsuke Meike; Saori Kobayashi; Mikinori Kuwabara; Osamu Inanami
    CANCER LETTERS, 277, 1, 64, 71, May 2009, [Peer-reviewed]
    English, Scientific journal
  • Inhibition of HIF-1 alpha by the anticancer drug TAS106 enhances X-ray-induced apoptosis in vitro and in vivo
    H. Yasui; A. Ogura; T. Asanuma; A. Matsuda; I. Kashiwakura; M. Kuwabara; O. Inanami
    BRITISH JOURNAL OF CANCER, 99, 9, 1442, 1452, Oct. 2008, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Visualization of the protective ability of a free radical trapping compound against rat C6 and F98 gliomas with diffusion tensor fiber tractography
    Taketoshi Asanuma; Sabrina Doblas; Yasvir A. Tesiram; Debra Saunders; Rebecca Cranford; Hironobu Yasui; Osamu Inanami; Nataliya Smith; Robert A. Floyd; Yashige Kotake; Rheal A. Towner
    JOURNAL OF MAGNETIC RESONANCE IMAGING, 28, 3, 574, 587, Sep. 2008, [Peer-reviewed]
    English, Scientific journal
  • A BOLD-fMRI study of cerebral activation induced by injection of algesic chemical substances into the anesthetized rat forepaw
    Taketoshi Asanuma; Hironobu Yasui; Masayasu Sato; Osamu Inanami; Mikinori Kuwabara
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 56, 2, 99, 107, Aug. 2008, [Peer-reviewed]
    English, Scientific journal
  • X irradiation combined with TNF alpha-related apoptosis-inducing ligand (TRAIL) reduces hypoxic regions of human gastric adenocarcinoma xenografts in SCID mice
    Momoko Takahashi; Hironobu Yasui; Aki Ogura; Taketoshi Asanuma; Nobuo Kubota; Michihiko Tsujitan; Mikinori Kuwabara; Osamu Inanami
    JOURNAL OF RADIATION RESEARCH, 49, 2, 153, 161, Mar. 2008, [Peer-reviewed]
    English, Scientific journal
  • Radiation-induced apoptosis of tumor cells is facilitated by inhibition of the interaction between Survivin and Smac/DIABLO
    Aki Ogura; Yasuko Watanabe; Daisuke Iizuka; Hironobu Yasui; Makoto Amitani; Saorl Kobayashi; Mikinori Kuwabara; Osamu Inanami
    CANCER LETTERS, 259, 1, 71, 81, Jan. 2008, [Peer-reviewed]
    English, Scientific journal
  • Enhancement of cell death by TNF alpha-related apoptosis-inducing ligand (TRAIL) in human lung carcinoma A549 cells exposed to X rays under hypoxia
    Momoko Takahashi; Osamu Inanami; Nobuo Kubota; Michihiko Tsujitan; Hironobu Yasui; Aki Ogura; Mikinori Kuwabara
    JOURNAL OF RADIATION RESEARCH, 48, 6, 461, 468, Nov. 2007, [Peer-reviewed]
    English, Scientific journal
  • Treatment combining X-irradiation and a ribonucleoside anticancer drug, TAS106, effectively suppresses the growth of tumor cells transplanted in mice
    Hironobu Yasui; Osamu Inanami; Taketoshi Asanuma; Daisuke Iizuka; Takayuki Nakajima; Yasuhiro Kon; Akira Matsuda; Mikinori Kumwabara
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 68, 1, 218, 228, May 2007, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Oral administration of Antioxidant Biofactor (AOB (TM)) ameliorates ischemia/reperfusion-induced neuronal death in the gerbil
    Hironobu Yasui; Taketoshi Asanuma; Yasuko Watanabe; Kenji Waki; Osamu Inanami; Mikinori Kuwabara
    BIOFACTORS, 29, 2-3, 113, 121, 2007, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • A new Amphiphilic derivative, N-{[4-(lactobionamido)methyl]benzylidene}1,1-dimethyl-2-(octylsulfanyl)ethylamine N-oxide, has a protective effect against copper-induced fulminant hepatitis in Long-Evans Cinnamon rats at an extremely low concentration compared with its original form alpha-phenyl-N-(tert-butyl) nitrone
    Taketoshi Asanuma; Hironobu Yasui; Osamu Inanami; Kenji Waki; Momoko Takahashi; Daisuke Iizuka; Taketo Uemura; Gregory Durand; Ange Polidori; Yasuhiro Kon; Bernard Pucci; Mikinori Kuwabara
    CHEMISTRY & BIODIVERSITY, 4, 9, 2253, 2267, 2007, [Peer-reviewed], [Lead author]
    English, Scientific journal
■ Other Activities and Achievements
■ Books and other publications
■ Lectures, oral presentations, etc.
  • 放射線照射およびフェロトーシス誘導後の腫瘍内レドックス変化に対する電子スピン共鳴イメージングによる非侵襲的空間解析
    安井博宣; 加藤千博; 赤羽英夫; 江本美穂; 藤井博匡; 永根大幹; 山下匡; 稲波修
    第25回菅原・大西記念癌治療増感シンポジウム, 01 Feb. 2025, Japanese, Public symposium
    01 Feb. 2025 - 02 Feb. 2025, [Invited]
  • 酸化ストレスを受けたHeLa細胞の失活アコニターゼと細胞内遊離鉄イオンのESRによる検出
    稲波修; 安井博宣; 平岡和佳子; 櫻井敬博; 大久保晋; 太田仁
    第63回電子スピンサイエンス学会年会, 02 Nov. 2024, Japanese, Oral presentation
    02 Nov. 2024 - 04 Nov. 2024
  • 企画専門委員会の活動-令和6年度教育訓練講習会アンケート調査結果とその考察-
    山本由美; 稲田晋宣; 上髙祐人; 柴田理尋; 谷口真; 中島裕美子; 福島芳子; 牧大介; 安井博宣
    令和6年度放射線安全取扱部会年次大会, 17 Oct. 2024, Japanese, Poster presentation
    17 Oct. 2024 - 18 Oct. 2024
  • 放射線によるミトコンドリア機能不全は血管内皮細胞の細胞老化を促進する
    永根大幹; 山下晃矢; 鈴木武人; 荻原喜久美; 村上裕信; 安井博宣; 稲波修; 納谷裕子; 山下匡
    日本放射線影響学会第67回大会, 27 Sep. 2024, Japanese, Oral presentation
    25 Sep. 2024 - 28 Sep. 2024
  • 放射線誘発細胞老化とがん治療標的としての可能性
    安井博宣; 杉山萌々子; 小澤拓実; 山下晃矢; 加藤千博; 稲波修
    日本放射線影響学会第67回大会, 25 Sep. 2024, Japanese, Nominated symposium
    25 Sep. 2024 - 28 Sep. 2024, [Invited]
  • 放射線照射に対するミトコンドリアエネルギー代謝応答と細胞老化
    稲波修; 安井博宣
    日本放射線影響学会第67回大会, 25 Sep. 2024, Japanese, Nominated symposium
    25 Sep. 2024 - 28 Sep. 2024, [Invited]
  • 放射線誘発性細胞老化に対するサバイビン阻害剤YM155 によるin vivo セノリシス効果に関する研究
    杉山萌々子; 安井博宣; 山下晃矢; 加藤千博; 稲波修
    日本放射線影響学会第67回大会, 25 Sep. 2024, Japanese, Oral presentation
    25 Sep. 2024 - 28 Sep. 2024
  • The potential of 68Ga-labeled TfRB1G3 as a novel PET imaging agent targeting TfR1 in tumors
    Lin L.; Mizuno Y.; Shibata Y.; Yasui H.; Kuge Y.
    the 12th China-Japan-Korea Symposium on Radiopharmaceutical Sciences (CJKSRS2024), 19 Sep. 2024, English, Oral presentation
    19 Sep. 2024 - 20 Sep. 2024
  • 殺細胞効果を有する液体の膀胱内注入治療法の検討
    佐々木東; 池中良徳; 安井博宣; 中村健介; 滝口満喜
    第167回日本獣医学会学術集会, 13 Sep. 2024, Japanese, Oral presentation
    10 Sep. 2024 - 13 Sep. 2024
  • インビボにおけるフェロトーシス検出のための電子常磁性共鳴イメージングと免疫組織化学染色の併用による基礎研究
    加藤千博; 安井博宣; 赤羽英夫; 江本美穂; 藤井博匡; 永根大幹; 山下匡; 稲波修
    第167回日本獣医学会学術集会, 12 Sep. 2024, Japanese, Oral presentation
    10 Sep. 2024 - 13 Sep. 2024
  • DNA 量の不均一性を有するがん細胞株における放射線分割照射後の放射線抵抗性がん細胞の出現機構の解析
    山下晃矢; 安井博宣; 房知輝; 藤本政毅; 稲波修
    第167回日本獣医学会学術集会, 12 Sep. 2024, Japanese, Oral presentation
    10 Sep. 2024 - 13 Sep. 2024
  • サバイビン阻害剤YM155による老化細胞選択的除去法のがん治療応用に関する研究
    杉山萌々子; 安井博宣; 山下晃矢; 加藤千博; 稲波修
    第167回日本獣医学会学術集会, 12 Sep. 2024, Japanese, Oral presentation
    10 Sep. 2024 - 13 Sep. 2024
  • Multimodal imaging for redox status and glucose metabolism in tumor
    Inanami O.; Kato K.; Sato-Akaba H.; Emoto MC; Fujii HG; Mizuno Y.; Kuge Y.; Nagane M.; Yamashita T.; Yasui H.
    International Workshop "Modern developments and applications of ESR, THz and high magnetic fields" (MDETH 2024), 03 Sep. 2024, English, Oral presentation
    03 Sep. 2024 - 05 Sep. 2024
  • サバイビン阻害剤YM155 による老化がん細胞選択的除去法
    杉山萌々子; 安井博宣; 山下晃矢; 加藤千博; 稲波修
    フリーラジカルスクール2024, 07 Aug. 2024, Japanese, Oral presentation
    07 Aug. 2024 - 08 Aug. 2024
  • Detection of Inactivated Aconitase in Human Cervical Carcinoma HeLa Cells by EPR Spectroscopy at 12K and Effects of Ionizing Radiation on Aconitase Activity
    Inanami O.; Kato K.; Hiraoka W.; Sakurai T.; Okubo S.; Ohta H.
    63rd Annual Rocky Mountain Conference on Magnetic Resonance, 04 Aug. 2024, English, Poster presentation
    04 Aug. 2024 - 08 Aug. 2024
  • マウス移植腫瘍における酸化還元状態とグルコース代謝の関連性
    稲波修; 加藤千博; 赤羽英夫; 藤井博匡; 江本美穂; 水野雄貴; 久下裕司; 永根大幹; 山下匡; 安井博宣
    第61回日本生化学会北海道支部例会, 14 Jul. 2024, Japanese, Oral presentation
    14 Jul. 2024 - 14 Jul. 2024
  • Self-assembled nanoparticle releasing dichloroacetic acid sensitized X-ray irradiation in a murine tumor model
    Omori F.; Yamada S.; Nagasaki Y.; Inanami O.; Yasui H.
    The 40th Annual Meeting of the Japan Society of Drug Delivery System, 10 Jul. 2024, English, Oral presentation
    09 Jul. 2024 - 11 Jul. 2024
  • マウス扁平上皮癌におけるジクロロ酢酸解離型ナノ粒子の放射線増感作用
    大森史裕; 山田さと; 長崎幸夫; 稲波修; 安井博宣
    第40回 日本DDS学会学術集会, 09 Jul. 2024, Japanese, Oral presentation
    09 Jul. 2024 - 11 Jul. 2024
  • マウスがん細胞におけるSTING阻害による放射線照射後の老化誘導の抑制と細胞死増感効果に関する検討
    安井博宣; 佐藤清やか; 稲波修
    第28回癌治療増感研究会, 29 Jun. 2024, Japanese, Oral presentation
    29 Jun. 2024 - 29 Jun. 2024
  • Tumor extracellular pH response to carbonic anhydrase IX inhibitor U-104 on mouse xenograft models
    Nakaoka R.; Kato K.; Yamamoto K.; Yasui H.; Matsumoto S.; Kirilyuk IA; Khramtsov VV; Inanami O.; Hirata H.
    51st Annual Meeting of the International Society on Oxygen Transport to Tissue (ISOTT), 09 Jun. 2024, English, Poster presentation
    09 Jun. 2024 - 14 Jun. 2024
  • 電子常磁性共鳴レドックスイメージングを用いた空間的解析によるX線またはフェロトーシス誘導に対する腫瘍の治療応答の解明
    加藤千博; 安井博宣; 赤羽英夫; 江本美穂; 藤井博匡; 永根大幹; 山下匡; 稲波修
    第77回日本酸化ストレス学会学術集会, 18 May 2024, Japanese, Oral presentation
    17 May 2024 - 19 May 2024
  • がん特異的代謝と放射線感受性
    安井博宣
    第14回放射線生物学セミナー, 16 Mar. 2024, Japanese, Public discourse
    [Invited]
  • Redox imaging of tumors with a novel compact and portable EPRI device and its potential for multimodal imaging
    Kato K; Yasui H; Sato-Akaba H; Emoto MC; Fujii HG; Mizuno Y; Kuge Y; Nagane M; Yamashita T; Inanami O
    The Annual Meeting of the Society for Free Radical Biology and Medicine 2023 & SFRRI 21st Biennial Meeting, 15 Nov. 2023, English, Poster presentation
    15 Nov. 2023 - 18 Nov. 2023
  • マウス扁平上皮癌におけるジクロロ酢酸を放出する自己組織化ナノ粒子の放射線増感作用について
    山田さと; 安井博宣; 長崎幸夫; 稲波修
    日本放射線影響学会第66回大会, 06 Nov. 2023, Japanese, Poster presentation
    06 Nov. 2023 - 08 Nov. 2023
  • 腫瘍内におけるDNA 量の不均一性が放射線分割照射後の放射線抵抗性がん細胞の出現につながる
    山下晃矢; 安井博宣; 房知輝; 藤本政毅; 稲波修
    日本放射線影響学会第66回大会, 06 Nov. 2023, Japanese, Oral presentation
    06 Nov. 2023 - 08 Nov. 2023
  • マウス扁平上皮がん細胞SCCVIIにおける、Pluronic L64 で修飾したC60 フラーレン(C60/L64)の放射線増感効果
    臼田史仁; 加藤千博; 安井博宣; 王鈺博; 山本拓矢; 稲波修
    日本放射線影響学会第66回大会, 06 Nov. 2023, Japanese, Poster presentation
    06 Nov. 2023 - 08 Nov. 2023
  • 4 次元スペクトル空間EPR イメージングにおける計測時間短縮法の提案
    大場光紗; 田口真衣; 工藤洋平; 山下晃矢; 安井博宣; 松元慎吾; Kirilyuk I.A; 稲波修; 平田拓
    第62回電子スピンサイエンス学会年会, 02 Nov. 2023, Japanese, Oral presentation
    02 Nov. 2023 - 04 Nov. 2023
  • 電子常磁性共鳴イメージングと免疫組織化学染色の比較による腫瘍におけるフェロトーシス検出の可能性
    加藤千博; 安井博宣; 赤羽英夫; 江本美穂; 藤井博匡; 永根大幹; 山下匡; 稲波修
    第62回電子スピンサイエンス学会年会, 02 Nov. 2023, Japanese, Oral presentation
    02 Nov. 2023 - 03 Nov. 2023
  • 企画専門委員会の活動-令和5年度教育訓練講習会アンケート調査結果とその考察-
    渡部浩司; 池田岳紡; 稲田晋宣; 北実; 谷口真; 中島裕美子; 牧大介; 安井博宣; 山本由美
    令和5年度放射線安全取扱部会年次大会, 26 Oct. 2023, Japanese, Poster presentation
    26 Oct. 2023 - 27 Oct. 2023
  • Tumor extracellular pH mapping using electron paramagnetic resonance: Recent progress and applications
    Nakaoka R; Kato K; Yamamoto K; Yasui H; Matsumoto S; Kirilyuk I.A; Khramtsov V.V; Inanami O; Hirata H
    The 22nd IEEE International Symposium on Mixed and Augmented Reality (ISMAR2023), 16 Oct. 2023, English, Invited oral presentation
    16 Oct. 2023 - 20 Oct. 2023
  • Partial acquisition of spectral projections accelerates four-dimensional spectral-spatial EPR imaging for mouse tumor models: A feasibility study
    Oba M; Taguchi M; Kudo Y; Yamashita K; Yasui H; Matsumoto S; Kirilyuk IA; Inanami O; Hirata H
    50th Annual ISOTT Meeting, 27 Sep. 2023, English, Oral presentation
    27 Sep. 2023 - 01 Oct. 2023
  • Investigation of the roles of histone lactylation and glutamine metabolism in canine hemangiosarcoma
    鈴木 玲海; 青島 圭佑; 山﨑 淳平; 安井 博宣; 平島 一輝; 木村 享史
    第82回日本癌学会学術総会, 21 Sep. 2023, Japanese, Poster presentation
    21 Sep. 2023 - 23 Sep. 2023
  • Effects of ionizing radiation on mitochondria dependent reactive oxygen species in mammalian cancer cells
    Inanami O; Kato K; Goto Y; Hiraoka W; Ogawa M; Yasui H
    17th International Congress of Radiation Research, 27 Aug. 2023, English, Poster presentation
    27 Aug. 2023 - 30 Aug. 2023
  • Senolytic effect of a survivin inhibitor YM155 on X-irradiation-induced senescence in cancer cells
    Yasui H; Ozawa T; Yamashita K; Kato K; Inanami O
    17th International Congress of Radiation Research, 27 Aug. 2023, English, Poster presentation
    27 Aug. 2023 - 30 Aug. 2023
  • Promising methods for radiotherapy using molecular imaging and radioisotopes
    Yasui H
    10th GCB Summer School for Medical Physics and the 6th GCB Summer School for Molecular Biomedical Science and Engineering, 21 Aug. 2023, English, Public discourse
    21 Aug. 2023 - 25 Aug. 2023, [Invited]
  • Analyses of Roles of Histone Lactylation and Glucose Metabolism in Canine Hemangiosarcoma
    Suzuki T; Aoshima K; Yamazaki J; Yasui H; Okamatsu-Ogura Y; Heishima K; Kimura T
    The annual meeting of the International Society of Organoid Research (ISoOR2023), 07 Aug. 2023, English, Poster presentation
    07 Aug. 2023 - 08 Aug. 2023
  • イメージングを基盤とする放射線治療の効率化に向けた開発研究
    安井博宣
    第26回癌治療増感研究会, 30 Jun. 2023, Japanese, Invited oral presentation
    30 Jun. 2023 - 01 Jul. 2023, [Invited]
  • 18F-FDG PET/MRI によるマウス網膜変性疾患モデルの評価
    松元慎吾; 須藤志保; 安井博宣; 水野雄貴; 久下裕司; 山田健一; 平田拓
    第17 回日本分子イメージング学会総会・学術集会, 08 Jun. 2023, Japanese, Poster presentation
    08 Jun. 2023 - 09 Jun. 2023
  • イヌ血管肉腫におけるヒストンラクチル化とグルタミン代謝の役割の解析
    鈴木 玲海; 青島 圭佑; 山﨑 淳平; 安井 博宣; 平島 一輝; 木村 享史
    第9回がんと代謝研究会, 31 May 2023, Japanese, Poster presentation
    31 May 2023 - 01 Jun. 2023
  • Synthesis of [64Cu]Cu+ complex for redox imaging and evaluation of its reactivity with reactive oxygen species
    Tada T; Mizuno Y; Shibata Y; Yasui H; Kuge Y
    The 25th International Symposium on Radiopharmaceutical Sciences (ISRS2023), 22 May 2023, English, Poster presentation
    22 May 2023 - 26 May 2023
  • The synthesis and evaluation of [68Ga]Ga-HBED-CC-TfRB1G3 for TfR1 imaging.
    Lin L; Mizuno Y; Shibata Y; Yasui H; Kuge Y
    The 25th International Symposium on Radiopharmaceutical Sciences (ISRS2023), 22 May 2023, English, Poster presentation
    22 May 2023 - 25 May 2023
  • スフィンゴミエリン合成酵素2は虚血性筋障害を促進する
    水垣ひなの; 永根大幹; 赤羽英夫; Kuppusamy Periannan; 安井博宣; 稲波修; 相原尚之; 上家潤一; 水野谷航; 山下匡
    第76 回日本酸化ストレス学会学術集会, 24 Apr. 2023, Japanese, Oral presentation
    24 Apr. 2023 - 25 Apr. 2023
  • 放射線によるDNA損傷は遅延性のミトコンドリア由来の細胞内活性酸素種を上昇させるか?
    稲波修; 加藤千博; 安井博宣; 後藤悠人; 小川美香子
    第76 回日本酸化ストレス学会学術集会, 24 Apr. 2023, Japanese, Poster presentation
    24 Apr. 2023 - 25 Apr. 2023
  • Cystine-dense peptide TfRB1G3 のTfR1への親和性評価と68Ga標識に向けたHBED-CC結合体合成
    林龍昕; 水野雄貴; 久下裕司; 柴田悠貴; 安井博宣
    日本薬学会第143年会, 25 Mar. 2023, Japanese, Poster presentation
    25 Mar. 2023 - 28 Mar. 2023
  • スフィンゴミエリンは虚血性筋障害を増悪させる
    水垣ひなの; 永根大幹; 赤羽英夫; Kmiec Maciej; Kuppusamy Periannan; 安井博宣; 稲波修; 相原尚之; 上家潤一; 水野谷航; 山下匡
    Free Radical School 2022, 23 Feb. 2023, Japanese, Oral presentation
    23 Feb. 2023 - 24 Feb. 2023
  • レドックスと糖代謝の非侵襲的なマルチモーダルイメージングによるがん治療応答変化の解析
    加藤千博; 安井博宣; 赤羽英夫; 藤井博匡; 江本美穂; 永根大幹; 山下匡; 稲波修
    Free Radical School 2022, 23 Feb. 2023, Japanese, Oral presentation
    23 Feb. 2023 - 24 Feb. 2023
  • 分割照射により樹立した放射線抵抗性大腸がんSW480RR 細胞株はDNA 量と放射線によるDNA 損傷が少ない
    山下晃矢; 房知輝; 藤本政毅; 安井博宣; 辻雅久; 稲波修
    Free Radical School 2022, 23 Feb. 2023, Japanese, Oral presentation
    23 Feb. 2023 - 24 Feb. 2023
  • 腫瘍のレドックスと糖代謝の非侵襲的なマルチモーダルイメージング解析に向けた基礎的検討
    加藤千博; 安井博宣; 赤羽英夫; 藤井博匡; 江本美穂; 水野雄貴; 久下裕司; 永根大幹; 山下匡; 稲波修
    第23回菅原・大西記念癌治療増感シンポジウム, 04 Feb. 2023, Japanese, Oral presentation
    04 Feb. 2023 - 05 Feb. 2023
  • 分割照射による放射線抵抗性大腸がんSW480RR 細胞株の樹立においてDNA 量の差異が抵抗性に寄与する
    山下晃矢; 房知輝; 藤本政毅; 安井博宣; 辻雅久; 稲波修
    第23回菅原・大西記念癌治療増感シンポジウム, 04 Feb. 2023, Japanese, Oral presentation
    04 Feb. 2023 - 05 Feb. 2023
  • レドックスと糖代謝の同時イメージング解析による放射線治療効果の非侵襲的評価法の確立
    加藤千博; 安井博宣; 赤羽英夫; 藤井博匡; 江本美穂; 永根大幹; 山下匡; 稲波修
    第2回放射線影響研究会, 07 Jan. 2023, Japanese, Oral presentation
    07 Jan. 2023
  • 腫瘍のレドックスと糖代謝の非侵襲的な複合画像機能解析に向けた基礎的検討
    加藤千博; 安井博宣; 赤羽英夫; 藤井博匡; 江本美穂; 永根大幹; 山下匡; 稲波修
    第35回日本酸化ストレス学会関東支部会, 17 Dec. 2022, Japanese, Oral presentation
    17 Dec. 2022 - 17 Dec. 2022
  • 可搬型EPRI 装置を用いた非侵襲的レドックスイメージングによる同一個体でのがん治療応答変化の解析
    加藤千博; 安井博宣; 赤羽英夫; 藤井博匡; 江本美穂; 永根大幹; 山下匡; 稲波修
    第61回電子スピンサイエンス学会年会, 02 Dec. 2022, Japanese, Oral presentation
    02 Dec. 2022 - 04 Dec. 2022
  • スフィンゴミエリン合成酵素2の虚血性筋疾患における機能
    水垣ひなの; 永根大幹; 赤羽英夫; Kmiec Maciej; Kuppusamy Periannan; 水野谷航; 安井博宣; 稲波修; 相原尚之; 上家潤一; 山下匡
    第61回電子スピンサイエンス学会年会, 02 Dec. 2022, Japanese, Oral presentation
    02 Dec. 2022 - 04 Dec. 2022
  • 低酸素性がん細胞における光免疫療法(PIT)と光線力学的療法(PDT)の殺細胞効果の比較・検討
    白川晴香; 後藤悠人; 中島孝平; 高倉栄男; 安井博宣; 小川美香子; 稲波修
    第61回電子スピンサイエンス学会年会, 02 Dec. 2022, Japanese, Oral presentation
    02 Dec. 2022 - 04 Dec. 2022
  • 老化細胞制御から見える放射線治療の新展開
    安井博宣; 稲波修
    日本放射線腫瘍学会第35回学術大会, 10 Nov. 2022, Japanese, Invited oral presentation
    10 Nov. 2022 - 12 Nov. 2022, [Invited]
  • 虚血性筋障害におけるスフィンゴミエリン合成酵素2の役割
    水垣ひなの; 永根大幹; 佐藤沙菜; 水野谷航; 赤羽英夫; Kmiec Maciej; Kuppusamy Periannan; 安井博宣; 稲波修; 相原尚之; 上家潤一; 山下匡
    第95回日本生化学会大会, 09 Nov. 2022, Japanese, Oral presentation
    09 Nov. 2022 - 11 Nov. 2022
  • Cystine-dense peptideを母体としたTfR1イメージング薬剤開発に向けた基礎的検討
    林龍昕; 水野雄貴; 柴田悠貴; 安井博宣; 久下裕司
    第8北大部局横断シンポジウム, 28 Oct. 2022, Japanese, Poster presentation
  • 企画専門委員会の活動-令和4年度教育訓練講習会アンケート調査結果とその考察-
    渡部浩司; 池田岳紡; 稲田晋宣; 北実; 谷口真; 中島裕美子; 牧大介; 安井博宣; 山本由美
    令和4年度放射線安全取扱部会年次大会, 13 Oct. 2022, Japanese, Oral presentation
    13 Oct. 2022 - 14 Oct. 2022
  • EPR implemented with multiple harmonic detection successfully maps extracellular pH n vivo
    Nakaoka R; Kato K; Yamamoto K; Yasui H; Matsumoto S; Kirilyuk I.A; Khramtsov V.V; Inanami O; Hirata H
    12th International Workshop on EPR in Biology and Medicine, 10 Oct. 2022, English, Nominated symposium
  • レドックスイメージングを目的とした[64Cu][CuI(BCS)2]+の合成とROSとの反応性評価
    多田哲朗; 水野雄貴; 柴田悠貴; 安井博宣; 久下裕司
    第5回日本核医学会分科会放射性薬品科学研究会/第21回放射性医薬品・画像診断薬研究会, 17 Sep. 2022, Japanese, Oral presentation
  • 新しい可搬型EPRI装置を用いた腫瘍内レドックスイメージングによる放射線治療応答の非侵襲的解析
    加藤千博; 安井博宣; 赤羽英夫; 藤井博匡; 江本美穂; 永根大幹; 山下匡; 稲波修
    日本放射線影響学会第65回大会, 15 Sep. 2022, Japanese, Oral presentation
  • X線照射および抗がん剤によって生じるがん老化細胞に対するYM155のセノリシス作用に関する研究
    小澤拓実; 安井博宣; 加藤千博; 山下晃矢; 藤本政毅; 稲波修
    日本放射線影響学会第65回大会, 15 Sep. 2022, Japanese, Oral presentation
  • Redox-based imaging analysis with a novel portable EPRI device for tumor response to radiation
    Kato K; Yasui H; Sato-Akaba H; Fujii H; Emoto M; Nagane M; Yamashita T; Inanami O
    The 10th Sapporo Summer Seminar for One Health, 14 Sep. 2022, English, Poster presentation
  • Synthesis and evaluation of [64Cu]Cu+ complexes for reactive oxygen species (ROS) imaging
    多田哲朗; 水野雄貴; 柴田悠貴; 安井博宣; 久下裕司
    第62回日本核医学会学術総会, 09 Sep. 2022, English, Oral presentation
  • 可搬型EPRI装置を用いた腫瘍内レドックスイメージングによるがん治療応答解析
    加藤千博; 安井博宣; 赤羽英夫; 藤井博匡; 江本美穂; 永根大幹; 山下匡; 稲波修
    第165 回日本獣医学会学術集会, 06 Sep. 2022, Japanese, Oral presentation
  • 虚血性筋障害におけるスフィンゴミエリン合成酵素2の機能解析
    水垣ひなの; 永根大幹; 佐藤沙菜; 水野谷航; 赤羽英夫; 安井博宣; 稲波修; 藤井博匡; 相原尚之; 上家潤一; 山下匡
    第165 回日本獣医学会学術集会, 06 Sep. 2022, Japanese, Oral presentation
  • イヌ悪性黒色腫細胞株における放射線照射で生じる上皮間葉転換とDNAメチル化の関与
    田邊裕晶; 安井博宣; 山崎淳平; 木之下怜平; 山下晃矢; 加藤千博; 稲波修
    第165 回日本獣医学会学術集会, 06 Sep. 2022, Japanese, Oral presentation
  • 低酸素条件下のがん細胞に対する光免疫療法(PIT)の有効性の評価
    白川晴香; 後藤悠人; 中島孝平; 高倉栄男; 安井博宣; 小川美香子; 稲波修
    第165回日本獣医学会学術集会, 06 Sep. 2022, Japanese, Oral presentation
  • HCT116細胞におけるエトポシドによって生じる細胞老化の選択除去法に関する研究
    小澤拓実; 安井博宣; 加藤千博; 山下晃矢; 藤本政毅; 稲波修
    第165 回日本獣医学会学術集会, 06 Sep. 2022, Japanese, Oral presentation
  • Promising methods for radiotherapy using molecular imaging and radioisotopes
    Yasui H
    9th GCB Summer School for Medical Physics and the 5th GCB Summer School for Molecular Biomedical Science and Engineering, 22 Aug. 2022, English, Public discourse
    22 Aug. 2022 - 26 Aug. 2022, [Invited]
  • 放射線におけるセノリティック治療の可能性
    安井博宣; 藤本政毅; 小澤拓実; 稲波修
    第59回生物部会学術大会・第50回放射線による制癌シンポジウム, 22 Jun. 2022, Japanese, Nominated symposium
  • スフィンゴミエリン合成酵素2は重症下肢虚血での骨格筋再生を抑制する
    水垣ひなの; 永根大幹; 水野谷航; 赤羽英夫; 安井博宣; 稲波修; 藤井博匡; 相原尚之; 上家潤一; 山下匡
    第75 回日本酸化ストレス学会学術集会, 25 May 2022, Japanese, Oral presentation
  • トランスフェリン受容体認識直鎖ペプチドを母体とした68Ga標識プローブの合成と評価
    水野雄貴; 三浦春香; 安井博宣; 柴田悠貴; 大久保直登; 前原経; 武田宏司; 大西俊介; 久下裕司
    日本薬学会第142年会, 25 Mar. 2022, Japanese, Poster presentation
  • ROSイメージングを目的としたメタボリックトラップ型PETプローブの開発:CuI-BCA錯体の利用
    多田哲朗; 水野雄貴; 柴田悠貴; 安井博宣; 久下 裕司
    日本薬学会第142年会, 25 Mar. 2022, Japanese, Poster presentation
  • 酸化ストレスとがん治療
    安井博宣
    Free Radical School 2021, 14 Mar. 2022, Japanese, Public discourse
    [Invited]
  • Promising methods for radiotherapy using molecular imaging and radioisotopes
    Yasui H
    8th GI-CoRE GCB Summer School for Medical Physics & the 4th GI-CoRE GCB Summer School for Molecular Biomedical Science and Engineering, 28 Feb. 2022, English, Public discourse
    28 Feb. 2022 - 04 Mar. 2022, [Invited]
  • がん、酸化ストレス研究に役立つ磁気共鳴技術
    安井博宣
    第18回ESR夏の学校, 10 Feb. 2022, Japanese, Public discourse
    [Invited]
  • PET and MR imaging of physiological responses after near-infrared photoimmunotherapy for cancer
    Nakajima K; Sugikawa A; Yasui H; Higashikawa K; Takakura H; Suzuki C; Magata Y; Kuge Y; Ogawa M
    The 11th China-Japan-Korea Symposium on Radiopharmaceutical Sciences, 11 Nov. 2021, English, Poster presentation
  • 光免疫療法が腫瘍に及ぼす機能的変化に関するFDG-/FMISO-PETおよびMRIを用いた検討
    中島孝平; 杉川晃代; 安井博宣; 東川桂; 高倉栄男; 鈴木千恵; 間賀田泰寛; 久下裕司; 小川美香子
    第61回日本核医学会学術総会, 04 Nov. 2021, Japanese, Oral presentation
  • 企画専門委員会の活動-令和3年度教育訓練講習会アンケート調査結果とその考察-
    馬田敏幸; 池田岳紡; 稲田晋宣; 北実; 小山由起子; 安井博宣; 山本由美; 和田真由美; 渡部浩司
    令和3年度放射線安全取扱部会年次大会, 28 Oct. 2021, Japanese, Poster presentation
    28 Oct. 2021 - 29 Oct. 2021
  • ROSイメージングを目的としたメタボリックトラップ型PETプローブの開発:CuI-イソニトリル錯体の利用
    多田哲朗; 水野雄貴; 柴田悠貴; 安井博宣; 久下裕司
    第7回北大部局横断シンポジウム, 01 Oct. 2021, Japanese, Poster presentation
  • Evaluation of biological characteristics in photoimmunotherapy-treated tumors using PET and MRI
    中島孝平; 安井博宣; 東川桂; 高倉栄男; 久下裕司; 小川美香子
    第80回日癌学会学術総会, 30 Sep. 2021, Japanese, Oral presentation
  • セノリティック薬ABT263は非小細胞性肺がんにおいてグルタミン代謝阻害によって亢進した放射線誘発性細胞老化をアポトーシスに転換する
    藤本政毅; 東山りつ子; 安井博宣; 山下晃矢; 稲波修
    日本放射線影響学会第64回大会, 22 Sep. 2021, Japanese, Oral presentation
  • CAIX阻害剤とX線照射の併用による細胞内酸性化を介したアポトーシス誘導
    山下僚太; 安井博宣; 山下晃矢; 藤本政毅; 稲波修
    日本放射線影響学会第64回大会, 22 Sep. 2021, Japanese, Oral presentation
  • 中性アミノ酸輸送体LAT1阻害剤JPH203はmTOR活性を抑制することで放射線誘導性細胞老化を増強する
    房知輝; 小林翔; 稲波修; 藤井順逸; 中島修; 伊藤恒賢; 安井博宣
    日本放射線影響学会第64回大会, 22 Sep. 2021, Japanese, Oral presentation
  • Reduced DNA in colorectal cancer SW480RR cell line established by fractionated irradiation leads to radiation resistance.
    Yamashita K; Bo Tomoki; Fujimoto M; Yasui H; Tsuji M; Inanami O
    The 9th Sapporo Summer Seminar for One Health, 15 Sep. 2021, English, Poster presentation
  • A senolytic drug ABT263 can reduce side effect of cancer radiation therapy by inducing apoptosis in senescent cells
    Fujimoto M; Higashiyama R; Yasui H; Yamashita K; Inanami O
    The 9th Sapporo Summer Seminar for One Health, 15 Sep. 2021, English, Poster presentation
  • Characterization of tumor-specific hypoxia and therapeutic strategy to overcome it in radiation biology
    Yasui H
    The 9th Sapporo Summer Seminar for One Health, 15 Sep. 2021, English, Oral presentation
  • セノリティック薬ABT263のアポトーシス誘導およびSASP因子分泌抑制によるおよびSASP因子分泌抑制によるがん放射線治療による副作用の軽減効果の可能性
    藤本政毅; 東山りつ子; 安井博宣; 山下晃矢; 稲波修
    第164 回日本獣医学会学術集会, 07 Sep. 2021, Japanese, Oral presentation
  • X線照射およびCA9阻害による癌細胞の増殖抑制に関するメカニズムの検討
    山下僚太; 安井博宣; 山下晃矢; 藤本政毅; 稲波修
    第164 回日本獣医学会学術集会, 07 Sep. 2021, Japanese, Oral presentation
  • 培養がん細胞の治療を模倣した放射線照射に伴う放射線抵抗性獲得機構の解析
    山下晃矢; 房知輝; 藤本政毅; 安井博宣; 辻雅久; 稲波修
    第164 回日本獣医学会学術集会, 07 Sep. 2021, Japanese, Oral presentation
  • Evaluation of [18F]FDG uptake after anti PD-1 therapy in mice
    Tomita M; Yasui H; Higashikawa K; Nakajima K; Takakura H; Shiga T; Kuge Y; Ogawa M
    The 31st International Symposium on Pharmaceutical and Biomedical Analysis (PBA2021), 29 Aug. 2021, English
  • マウス乳がんモデルにおけるエリブリンと放射線の併用療法に対する18F-DiFA PET低酸素イメージングを用いた効果判定予測に関する検討
    安井博宣; 房知輝; 志賀哲; 柴田悠貴; 藤本政毅; 鈴木基史; 東川桂; 宮本直樹; 稲波修; 久下裕司
    第58回生物部会学術大会・第49回放射線による制癌シンポジウム, 04 Jun. 2021, Japanese, Oral presentation
  • ヒト肺腺がん由来 A549細胞においてグルタミノリシス阻害は放射線誘発性の細胞老化を亢進する
    藤本政毅; 東山りつ子; 安井博宣; 山下晃矢; 稲波修
    第74 回日本酸化ストレス学会学術集会/第21回日本NO学会, 19 May 2021, Japanese, Oral presentation
  • 企画専門委員会の活動-令和2年度教育訓練講習会アンケート調査結果とその考察-
    馬田敏幸; 池田岳紡; 稲田晋宣; 北実; 小山由起子; 安井博宣; 山本由美; 和田真由美; 渡部浩司
    令和2年度放射線安全取扱部会年次大会, 02 Nov. 2020, Japanese, Public discourse
  • チミジンホスホリラーゼ標的イメージングによる非アルコール性脂肪肝炎診断法の検討
    上原 里穂; 東川 桂; 水野雄貴; 堀口 紗和子; 大久保 直登; 安井 博宣; 久下 裕司; 武田 宏司
    第6回北大部局横断シンポジウム, 19 Oct. 2020, Japanese, Public symposium
  • 金属ナノ粒子によるがん放射線増感作用のメカニズムについて:DNA鎖が金ナノゲル粒子による放射線増感作用の主要な標的か?
    稲波修; 安井博宣; 山盛徹; 長崎幸夫
    日本放射線影響学会第63回大会, 15 Oct. 2020, Japanese, Nominated symposium
  • 分割照射によって出現した放射線抵抗性大腸がんSW480RR株化細胞の抵抗性メカニズムの解析
    山下晃矢; 房知輝; 藤本政毅; 安井博宣; 稲波修
    日本放射線影響学会第63回大会, 15 Oct. 2020, Japanese, Poster presentation
  • 放射線誘発性分裂期崩壊における中心体過剰複製の役割
    藤本政毅; 房知輝; 安井博宣; 山盛徹; 稲波修
    日本放射線影響学会第63回大会, 15 Oct. 2020, Japanese, Poster presentation
  • 18F-DiFA PET/CTイメージングを用いたエリブリンによる腫瘍内低酸素解除効果の解析と放射線増感作用の検討
    房知輝; 安井博宣; 志賀哲; 柴田悠貴; 藤本政毅; 鈴木基史; 東川桂; 宮本直樹; 稲波修; 久下裕司
    日本放射線影響学会第63回大会, 15 Oct. 2020, Japanese, Poster presentation
  • 分割照射によって出現した放射線抵抗性大腸がんSW480RR株化細胞の抵抗性メカニズムの解析
    山下晃矢; 房知輝; 藤本政毅; 安井博宣; 稲波修
    第73 回日本酸化ストレス学会学術集会/第20回日本NO学会, 06 Oct. 2020, Japanese, Poster presentation
  • ヒト肺腺がん由来A549細胞におけるグルタミノリシスが関与する細胞内レドックス調節と放射線感受性
    藤本政毅; 山下晃矢; 安井博宣; 稲波修
    第73 回日本酸化ストレス学会学術集会/第20回日本NO学会, 06 Oct. 2020, Japanese, Poster presentation
  • チミジンホスホリラーゼ標的プローブを非アルコール性脂肪肝炎診断に応用するためのin vivo機能解析
    上原里穂; 東川桂; 堀口紗和子; 足澤誠; 柴田悠貴; 大久保直登; 北浦廣剛; 安井博宣; 久下裕司; 武田宏司
    第3回日本核医学会分科会放射薬品科学研究会/第19回放射性医薬品・画像診断薬研究会, 30 Nov. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • A basic study on PET imaging technique for predicting cancer sensitivity to ferroptosis-targeting cancer therapy
    Shibata Y; Higashikawa K; Yasui H; Kuge Y
    The 26th Annual Meeting of the Society for Free Radical Biology and Medicine, 20 Nov. 2019, English, Poster presentation
    [International presentation]
  • ヒト肺腺がん A549細胞におけるグルタミノリシス阻害は放射線誘導性細胞老化を増強する
    東山りつ子; 安井博宣; 房知輝; 山本久美子; 藤本政毅; 稲波修
    日本放射線影響学会第62回大会, 14 Nov. 2019, Japanese, Poster presentation
    [Domestic Conference]
  • ヒト肺がん由来 A549細胞における解糖系の放射線応答性に関する研究
    福島佑一郎; 安井博宣; 藤本政毅; 山本久美子; 房知輝; 稲波修
    日本放射線影響学会第62回大会, 14 Nov. 2019, Japanese, Poster presentation
    [Domestic Conference]
  • 固形腫瘍株化細胞におけるエネルギー代謝の放射線応答の解析
    山本久美子; 安井博宣; 藤本政毅; 福島佑一郎; 房知輝; 稲波修
    日本放射線影響学会第62回大会, 14 Nov. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • ヒト肺腺がん由来 A549細胞においてグルタミノリシス依存性のエネルギー代謝の阻害は放射線の効果を増強する
    藤本政毅; 房知輝; 山本久美子; 安井博宣; 稲波修
    日本放射線影響学会第62回大会, 14 Nov. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • ミトコンドリア分裂とその Ca2+ 制御は照射後の分裂期崩壊に寄与する
    房知輝; 山盛徹; 山本久美子; 藤本政毅; 安井博宣; 稲波修
    日本放射線影響学会第62回大会, 14 Nov. 2019, Japanese, Public symposium
    [Domestic Conference]
  • ESR 法を用いた培養細胞における細胞外 pH 評価法の開発
    山本久美子; 安井博宣; 藤本政毅; 房知輝; Valery V. Khramtsov; 平田拓; 稲波修
    第57回電子スピンサイエンス学会年会, 07 Nov. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • ヒト肺腺がん由来A549細胞におけるグルタミノリシス阻害による放射線誘発性細胞死増強メカニズムの解明
    藤本政毅; 房知輝; 山本久美子; 安井博宣; 稲波修
    第5回北大部局横断シンポジウム, 06 Nov. 2019, Japanese, Poster presentation
    [Domestic Conference]
  • 陽子線照射中のがん細胞における亜致死損傷回復速度のLET依存性検証
    笠松幸生; 細田芽生; 南璡旼; 安井博宣; 田中創大; 平山嵩祐; 宮本直樹; 梅垣菊男; 白土博樹; 松浦妙子
    第5回北大部局横断シンポジウム, 06 Nov. 2019, Japanese, Poster presentation
    [Domestic Conference]
  • 超偏極核磁気共鳴法に裏付けされた細胞老化誘導治療の樹立
    安井博宣; 松元慎吾
    第5回北大部局横断シンポジウム, 06 Nov. 2019, Japanese, Poster presentation
    [Domestic Conference]
  • 光免疫療法が腫瘍に及ぼす変化に関する[18F]FDGと[18F]FMISOを用いた検討
    中島孝平; 杉川晃代; 安井博宣; 東川桂; 高倉栄男; 志賀哲; 久下裕司; 小川美香子
    第78回日本癌学会学術総会, 26 Sep. 2019, Japanese, Poster presentation
    [Domestic Conference]
  • Mitochondrial fission contributes to radiation-induced cell death by altering mitochondrial function
    Bo T; Yamamori T; Yamamoto K; Fujimoto M; Yasui H; Inanami O
    The 7th Sapporo Summer Seminar for One Health, 19 Sep. 2019, English, Oral presentation
    [International presentation]
  • Dependence of the Sub-Lethal Damage Repair Rate on LET in Proton Irradiation : An Initial Study
    Kasamatsu K; Hosoda M; Nam J.M; Yasui H; Tanaka S; Hirayama S; Miyamoto N; Umegaki K; Shirato H; Matsuura T
    第118回日本医学物理学会学術大会, 12 Sep. 2019, English, Poster presentation
    [Domestic Conference]
  • Glutamine代謝阻害がX線照射による早期細胞老化およびアポトーシスの誘導に与える影響の検討
    東山りつ子; 安井博宣; 房知輝; 山本久美子; 藤本政毅; 稲波修
    第162 回日本獣医学会学術集会, 10 Sep. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • ヒト肺腺がん由来A549細胞におけるグルタミノリシスを標的とする放射線増感効果
    藤本政毅; 房知輝; 山本久美子; 安井博宣; 稲波修
    第162 回日本獣医学会学術集会, 10 Sep. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • 種々のがん細胞におけるミトコンドリア電子伝達系の放射線応答の解析
    山本久美子; 安井博宣; 藤本政毅; 房知輝; 稲波修
    第162 回日本獣医学会学術集会, 10 Sep. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • ミトコンドリア分裂はCa2+制御を通じて放射線による分裂期崩壊誘導に寄与する
    房知輝; 山盛徹; 山本久美子; 藤本政毅; 安井博宣; 稲波修
    第162 回日本獣医学会学術集会, 10 Sep. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • In vivo extracellular pH mapping of tumor mouse models using EPR
    Komarov D.A; Ichikawa Y; Yamamoto K; Stewart N.J; Matsumoto S; Yasui H; Kirilyuk I.A; Khramtsov V.V; Inanami O; Hirata H
    XIth Conference of European Federation of EPR Groups (EFEPR), 01 Sep. 2019, English, Invited oral presentation
    [Invited], [International presentation]
  • X-Irradiation enhances energy metabolism derived from mitochondrial electron transport chain and glycolysis in cancer cells
    Yamamoto K; Yasui H; Bo T; Fujimoto M; Fukushima Y; Hiraoka W; Inanami O
    16th International Congress of Radiation Research, 25 Aug. 2019, English, Poster presentation
    [International presentation]
  • Inhibition of mitochondrial fission reduces radiation-induced mitotic catastrophe via Ca2+ regulation
    Bo T; Yamamori T; Yamamoto K; Fujimoto M; Yasui H; Inanami O
    16th International Congress of Radiation Research, 25 Aug. 2019, English, Poster presentation
    [International presentation]
  • チミジンホスホリラーゼ標的核医学イメージングプローブを用いた非侵襲的NASH診断法の開発研究
    東川桂; 上原里穂; 堀口紗和子; 柴田悠貴; 足澤誠; 北浦廣剛; 安井博宣; 武田宏司; 久下裕司
    第72 回日本酸化ストレス学会学術集会, 27 Jun. 2019, Japanese, Nominated symposium
    [Domestic Conference]
  • 放射線治療を併用したフェロトーシス誘導がん治療法の検討
    柴田悠貴; 安井博宣; 東川桂; 宮本直樹; 久下裕司
    第72 回日本酸化ストレス学会学術集会, 27 Jun. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • イヌ骨肉腫細胞株由来Cancer stem-like cellsのミトコンドリアの放射線反応性の解析
    出口辰弥; 細谷謙次; 金尚昊; 山本久美子; 房知輝; 安井博宣; 稲波修; 奥村正裕
    第72 回日本酸化ストレス学会学術集会, 27 Jun. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • ESR法によるがん細胞のミトコンドリア機能の放射線応答の解析
    山本久美子; 安井博宣; 房知輝; 藤本政毅; 稲波修
    第72 回日本酸化ストレス学会学術集会, 27 Jun. 2019, Japanese, Poster presentation
    [Domestic Conference]
  • ヒト肺腺がん由来A549細胞のエネルギー代謝におけるグルタミノリシス依存性とその放射線応答
    藤本政毅; 房知輝; 山本久美子; 安井博宣; 稲波修
    第72 回日本酸化ストレス学会学術集会, 27 Jun. 2019, Japanese, Poster presentation
    [Domestic Conference]
  • 放射線誘発細胞死に対するミトコンドリア分裂の寄与メカニズムの検討
    房知輝; 山盛徹; 山本久美子; 藤本政毅; 安井博宣; 稲波修
    第72 回日本酸化ストレス学会学術集会, 27 Jun. 2019, Japanese, Poster presentation
    [Domestic Conference]
  • Evaluation of [18F]FDG uptake after anti PD-1 therapy in mice
    Tomita M; Yasui H; Higashikawa K; Nakajima K; Takakura H; Shiga T; Kuge Y; Ogawa M
    SNMMI 2019 Annual Meeting, 22 Jun. 2019, English, Poster presentation
    [International presentation]
  • ミトコンドリア形態制御機構を標的とした放射線感受性変化の検討とそのメカニズムの解析
    房知輝; 山盛徹; 山本久美子; 藤本政毅; 安井博宣; 稲波修
    第57回日本放射線腫瘍学会生物部会学術大会, 07 Jun. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • Investigation of the potentials of a thymidine phosphorylase imaging probe for the differential diagnosis of nonalcoholic steatohepatitis
    Higashikawa K; Uehara R; Horiguchi S; Shibata Y; Tarisawa M; Kitaura H; Yasui H; Takeda H; Kuge Y
    The 23th International Symposium on Radiopharmaceutical Sciences (ISRS2019), 26 May 2019, English, Poster presentation
    [International presentation]
  • Preclinical evaluation of [18F]DiFA, a novel hypoxia PET probe, in a rat intracranial glioma model
    Yasui H; Higashikawa K; Shibata Y; Matsumoto H; Shiga T; Tamaki N. Kuge Y
    The 23th International Symposium on Radiopharmaceutical Sciences (ISRS2019), 26 May 2019, English, Oral presentation
    [International presentation]
  • 低酸素標的 PET プローブ[18F]DiFA のラット脳室内腫瘍モデルへの適用
    安井博宣; 東川桂; 柴田悠貴; 松本博樹; 志賀哲; 久下裕司
    第14 回日本分子イメージング学会総会・学術集会, 23 May 2019, Japanese, Poster presentation
    [Domestic Conference]
  • 光免疫療法による腫瘍環境の変化に関する[18F]FDG と[18F]FMISO を用いた検討
    中島孝平; 杉川晃代; 安井博宣; 東川桂; 高倉栄男; 志賀哲; 久下裕司; 小川美香子
    第14 回日本分子イメージング学会総会・学術集会, 23 May 2019, Japanese, Poster presentation
    [Domestic Conference]
  • がんのフェロトーシス感受性評価のためのイメージング法開発に向けた基礎的検討
    柴田悠貴; 東川桂; 安井博宣; 久下裕司
    第14 回日本分子イメージング学会総会・学術集会, 23 May 2019, Japanese, Poster presentation
    [Domestic Conference]
  • チミジンホスホリラーゼイメージングプローブを用いた非アルコール性脂肪肝炎の鑑別法の開発研究
    東川桂; 上原里穂; 堀口紗和子; 柴田悠貴; 足澤誠; 北浦廣剛; 安井博宣; 武田宏司; 久下裕司
    第14 回日本分子イメージング学会総会・学術集会, 23 May 2019, Japanese, Poster presentation
    [Domestic Conference]
  • 腫瘍内低酸素変動の可視化と放射線生物学における意義
    安井博宣
    第117回日本医学物理学会学術大会, 11 Apr. 2019, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • メトホルミンのイヌ骨肉腫細胞株由来のCancer stem-like cellsにおける放射線増感効果の解析
    出口辰弥; 細谷謙次; 金尚昊; 山本久美子; 房知輝; 安井博宣; 稲波修; 奥村正裕
    第21回菅原・大西記念癌治療増感シンポジウム, 02 Feb. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • ヒト肺腺がん由来A549細胞のエネルギー代謝におけるグルタミノリシス依存性とその放射線応答
    藤本政毅; 房知輝; 山本久美子; 安井博宣; 稲波修
    第21回菅原・大西記念癌治療増感シンポジウム, 02 Feb. 2019, Japanese, Oral presentation
    [Domestic Conference]
  • ホットセルに格納可能な小型RIガス貯留装置の開発
    阿保憲史; 野矢洋一; 東川桂; 安井博宣; 久下裕司
    日本放射線安全管理学会第17回学術大会, 05 Dec. 2018, Japanese, Oral presentation
    [Domestic Conference]
  • 新規低酸素トレーサー[18F]DiFAと[18F]FMISOの悪性腫瘍における低酸素集積の比較
    渡邊史郎; 平田健司; 小林健太郎; 安井博宣; 松本博樹; 久下裕司; 志賀哲
    第58回日本核医学会学術総会, 15 Nov. 2018, Japanese, Oral presentation
    [Domestic Conference]
  • 光免疫療法による[18F]FDGおよび[18F]FMISOの集積変化に関する検討
    中島孝平; 杉川晃代; 安井博宣; 東川桂; 高倉栄男; 志賀哲; 久下裕司; 小川美香子
    第58回日本核医学会学術総会, 15 Nov. 2018, Japanese, Oral presentation
    [Domestic Conference]
  • ESR法による新規ミトコンドリア機能評価法を用いたがん細胞の放射線応答の解析
    山本久美子; 安井博宣; 房知輝; 山盛徹; 稲波修
    日本放射線影響学会第61回大会, 07 Nov. 2018, Japanese, Oral presentation
    [Domestic Conference]
  • DNA 損傷応答は内皮型一酸化窒素合成酵素の活性化を介して血管内皮細胞を老化させる
    永根大幹; 安井博宣; 山盛徹; 稲波修; 山下匡; クプサミー ペリアナン
    日本放射線影響学会第61回大会, 07 Nov. 2018, Japanese, Poster presentation
    [Domestic Conference]
  • 電子スピン共鳴酸素イメージングによる脳室内移植グリオーマの放射線感受性評価
    安井博宣; 河合辰哉; 松元慎吾; 齋藤圭太; Kevin Camphausen; 稲波修; Murali C. Krishna
    日本放射線影響学会第61回大会, 07 Nov. 2018, Japanese, Poster presentation
    [Domestic Conference]
  • Potentials of a thymidine phosphorylase imaging agent in the diagnosis of nonalcoholic steatohepatitis
    Horiguchi S; Higashikawa K; Uehara R; Tarisawa M; Shibata Y; Ohkura K; Yasui H; Kuge Y; Takeda H
    the 10th China-Japan-Korea Symposium on Radiopharmaceutical Sciences (CJKSRS2018), 02 Nov. 2018, English, Oral presentation
    [International presentation]
  • マウス脳室内グリオーマモデルにおける放射線感受性評価へのESR酸素分圧イメージングの適用
    安井博宣; 河合辰哉; 松元慎吾; 齋藤圭太; Kevin Camphausen; Murali C. Krishna; 稲波修
    第57回電子スピンサイエンス学会年会, 01 Nov. 2018, Japanese, Poster presentation
    [Domestic Conference]
  • 新規ミトコンドリアストレス評価法を用いたがん細胞のミトコンドリア機能の解析
    山本久美子; 安井博宣; 房知輝; 藤本政毅; 稲波修
    第57回電子スピンサイエンス学会年会, 01 Nov. 2018, Japanese, Oral presentation
    [Domestic Conference]
  • 学内ネットワークを用いた被ばく記録のメール配信の試み
    野矢洋一; 阿保憲史; 東川桂; 安井博宣; 平田雄一; 久保直樹; 久下裕司
    平成30年度放射線安全取扱部会年次大会, 25 Oct. 2018, Japanese, Poster presentation
    仙台銀行ホール イズミティ21 (仙台市, 宮城), [Domestic Conference]
  • Longitudinal imaging of tumor oxygenation by pulsed ESR optimizes radiotherapy combined with a metabolic-targeted drug dichloroacetate in a murine squamous cell carcinoma model
    Yasui H; Saito K; Matsumoto S; Yamamori T; Krishna M.C; Inanami O
    3th Joint Conference of Asia-Pacific EPR/ESR Symposium - International EPR/ESR Society Symposium, 25 Sep. 2018, English, Oral presentation
    the University of Queensland (Brisbane, Australia), [Invited], [International presentation]
  • 非アルコール性脂肪肝炎の診断におけるチミジンホスホリラーゼイメージング剤の有用性の検討
    堀口紗和子; 東川桂; 上原里穂; 足澤誠; 柴田悠貴; 大倉一枝; 安井博宣; 久下裕司; 武田宏司
    第2回日本核医学会分科会放射薬品科学研究会/第18回放射性医薬品・画像診断薬研究会, 08 Sep. 2018, Japanese, Oral presentation
    東京都健康長寿医療センター研究所 (板橋区,東京), [Domestic Conference]
  • Promising methods for radiotherapy using molecular imaging and radioisotopes
    YASUI Hironobu
    Hokkaido Summer Institute 2018-Radiation Biology School, 02 Aug. 2018, English, Public discourse
    [Invited], [Domestic Conference]
  • Feasibility and potentials of thymidine phosphorylase (TP) as an imaging biomarker and its nuclear medicine imaging for the diagnosis of non-alcoholic steatohepatitis.
    Higashikawa K; Horiguchi S; Ebita Y; Tarisawa M; Komatsu Y; Ohkura K; Yasui H; Takeda H; Kuge Y
    24 Jun. 2018, English, Poster presentation
    Pennsylvania Convention Center (Philadelphia, PA), [International presentation]
  • チミジンホスホリラーゼイメージングプローブによる非アルコール性脂肪肝炎の診断法の開発研究
    東川桂; 堀口紗和子; 足澤誠; 小松由紀子; 大倉一枝; 安井博宣; 武田宏司; 久下裕司
    第13 回日本分子イメージング学会総会・学術集会, 31 May 2018, Japanese, Poster presentation
    東京大学 (文京区, 東京), [Domestic Conference]
  • 低酸素標的PETプローブ[18F]DiFAの腫瘍内局在に対するグルタチオン環境の影響評価
    安井博宣; 東川桂; 志水陽一; 松本博樹; 志賀哲; 玉木長良; 久下裕司
    第13 回日本分子イメージング学会総会・学術集会, 31 May 2018, Japanese, Oral presentation
    東京大学 (文京区, 東京), [Invited], [Domestic Conference]
  • 放射線照射および脂溶性TPP+化合物ががん細胞のミトコンドリア機能に与える影響の評価
    山本久美子; 安井博宣; 房知輝; 山盛徹; 平岡和佳子; 山崎俊栄; 山田健一; 稲波修
    第71 回日本酸化ストレス学会学術集会 / 第18 回日本NO学会 合同学術集会, 18 May 2018, Japanese, Poster presentation
    京都ホテルオークラ (京都市, 京都), [Domestic Conference]
  • 放射線は内皮型一酸化窒素合成酵素の活性化により血管内皮細胞の老化を誘導する
    永根大幹; 安井博宣; 山盛徹; 稲波修; 山下匡; クプサミー ペリアナン
    第71 回日本酸化ストレス学会学術集会 / 第18 回日本NO学会 合同学術集会, 17 May 2018, Japanese, Oral presentation
    京都ホテルオークラ (京都市, 京都), [Domestic Conference]
  • 新規ESRオキシメトリー法によるがん細胞のミトコンドリア電子伝達系の放射線応答の解析
    山本久美子; 安井博宣; 房知輝; 山盛徹; 稲波修
    量子生命科学研究会第2回学術集会, 10 May 2018, Japanese, Oral presentation
    東京大学 (文京区, 東京), [Domestic Conference]
  • [18F]DiFA, a new hypoxic imaging PET probe: A first human study in healthy subjects
    Watanabe S; Shiga T; Magota K; Hirata K; Okamoto S; Toyonaga T; Higashikawa K; Yasui H; Kobayashi J; Nishijima K.I; Iseki K; Matsumoto H; Kuge Y; Tamaki N
    WFNMB 2018, 22 Apr. 2018, English, Poster presentation
    the Melbourne Exhibition and Convention Centre (Melbourne, Australia), [International presentation]
  • Investigation of the influence of intratumoral glutathione status on the distribution of a hypoxic probe [18F]FMISO
    Yasui H; Higashikawa K; Shimizu Y; Shibata Y; Zhao S; Matsumoto H; Shiga T; Tamaki N; Kuge Y
    WFNMB 2018, 22 Apr. 2018, English, Poster presentation
    the Melbourne Exhibition and Convention Centre (Melbourne, Australia), [International presentation]
  • フェロトーシス誘導剤Erastinによる放射線増感効果の検討
    柴田悠貴; 安井博宣; 東川桂; 久下裕司
    日本薬学会第138年会, 28 Mar. 2018, Japanese, Oral presentation
    石川県立音楽堂 他 (金沢市, 石川), [Domestic Conference]
  • [18F]FDG PETを用いたPD-1治療効果の早期予測に関するin vivoでの検討
    安井 博宣富田真由; 高倉栄男; 安井博宣; 東川桂; 久下裕司; 小川美香子
    日本薬学会第138年会, 27 Mar. 2018, Japanese, Oral presentation
    石川県立音楽堂 他 (金沢市, 石川), [Domestic Conference]
  • ミトコンドリア依存性エネルギー代謝の放射線応答と電子伝達系阻害による放射線増感
    稲波修; 山本久美子; 房知輝; 山田健一; 安井博宣; 山盛徹
    第20回癌治療増感研究シンポジウム, 03 Feb. 2018, Japanese, Oral presentation
    奈良県文化会館 (奈良市, 奈良), [Domestic Conference]
  • 電子スピン共鳴pO2イメージングによる脳室内移植グリオーマのキャラクタリゼーション
    安井博宣; 河合辰哉; 松元慎吾; 齋藤圭太; Kevin Camphausen; 稲波修; Murali C. Krishna
    第20回癌治療増感研究シンポジウム, 03 Feb. 2018, Japanese, Oral presentation
    奈良県文化会館 (奈良市, 奈良), [Domestic Conference]
  • Three-Dimensional In Vivo Measurements of Tumor Acidification by Electron Paramagnetic Resonance Imaging
    Komarov D.A; Ichikawa Y; Stewart N; Yamamoto K; Matsumoto S; Yasui H; Kumiko Y; Inanami O; Hirata H
    第三回北大部局横断シンポジウム, 26 Jan. 2018, English, Oral presentation
    北海道大学 (札幌市, 北海道), [Domestic Conference]
  • ミトコンドリアイメージングによるフェロトーシス検出法の開発
    柴田悠貴; 安井博宣; 東川桂; 久下裕司
    第三回北大部局横断シンポジウム, 26 Jan. 2018, Japanese, Poster presentation
    北海道大学 (札幌市, 北海道), [Domestic Conference]
  • Quantitative pO(2) Mapping Using Electron Paramagnetic Resonance Imaging in Orthotopic Murine Glioma
    Yasui H; Kawai T; Matsumoto S; Saito K; Saito K; Devasahayam N; Mitchell J.B; Camphausen K; Inanami O; Krishna M
    The 20th Annual Meeting of the Society for Free Radical Biology and Medicine, 29 Nov. 2017, English, Poster presentation
    [International presentation]
  • 窒素同位体標識ニトロキシルラジカルによる腫瘍モデルマウスの酸素分圧イメージング
    久保田晴江; 安井博宣; 松元慎吾; 稲波修; Kirilyuk I.A; Khramtsov V.V; 平田拓
    第56回電子スピンサイエンス学会年会, 02 Nov. 2017, Japanese, Poster presentation
    [Domestic Conference]
  • 癌の低酸素およびエネルギー代謝が放射線感受性に及ぼす影響に関する研究
    安井博宣
    日本放射線影響学会第60回大会 奨励賞受賞講演, 25 Oct. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 全学放射線管理システムの更新とeラーニングによる教育訓練の試み
    野矢洋一; 阿保憲史; 東川桂; 安井博宣; 久下裕司
    平成29年度放射線安全取扱部会年次大会, 12 Oct. 2017, Japanese, Poster presentation
    [Domestic Conference]
  • 放射性ヨウ素標識チミジンホスホリラーゼイメージング剤の非アルコール性脂肪肝炎診断用プローブとしての可能性の検討
    東川桂; 堀口紗和子; 海老田曜子; 足澤誠; 小松由紀子; 大倉一枝; 安井博宣; 武田宏司; 久下裕司
    第57回日本核医学会学術総会, 05 Oct. 2017, Japanese, Oral presentation
    [Domestic Conference]
  • 腫瘍内グルタチオン環境が低酸素標的PETプローブ[18F]FMISOの分布に与える影響
    安井博宣; 東川桂; 志水陽一; 趙松吉; 松本博樹; 玉木長良; 久下裕司
    第160 回日本獣医学会学術集会, 13 Sep. 2017, Japanese, Oral presentation
    [Domestic Conference]
  • 非アルコール性脂肪肝炎診断用プローブとしてのチミジンホスホリラーゼイメージング剤の可能性の検討
    東川桂; 堀口紗和子; 海老田曜子; 足澤誠; 小松由紀子; 大倉一枝; 安井博宣; 武田 宏司; 久下裕司
    第1回放射性薬品科学研究会, 09 Sep. 2017, Japanese, Oral presentation
    [Domestic Conference]
  • マクロファージの極性化が18F-FMISOと125I-BMIPPの集積に及ぼす影響
    本村新; 志水陽一; 高倉栄男; 安井博宣; 東川桂; 玉木長良; 久下裕司; 小川美香子
    第1回放射性薬品科学研究会, 09 Sep. 2017, Japanese, Oral presentation
    [Domestic Conference]
  • Application of electron spin resonance (ESR/EPR) pO2 and redox imaging to improve cancer radiotherapy
    Yasui H
    2017 KSMI-FASMI Joint Conference, 25 Aug. 2017, English, Invited oral presentation
    [Invited], [International presentation]
  • Introduction to Radiation Biology
    Yasui H
    GI-CoRE 医学物理サマースクール2017, 21 Aug. 2017, English, Public discourse
    [Invited], [Domestic Conference]
  • Three-dimensional oxygen mapping using a pair of isotopic nitroxyl radicals and CW-EPR-based single-point imaging
    Kubota H; Komarov D.A; Matsumoto S; Yasui H; Kumiko Y; Inanami O; Kirilyuk I.A; Khramtsov V.V; Hirata H
    International Conference on Electron Paramagnetic Resonance Spectroscopy and Imaging of Biological Systems (EPR-2017), 16 Jul. 2017, English, Oral presentation
    [International presentation]
  • 転写調節因子Id1はp53依存的に放射線誘発細胞老化を抑制する
    安井博宣; 竹内麻依; 山盛徹; 松本英樹; 高橋昭久; 稲波修
    第23回癌治療増感研究会, 15 Jul. 2017, Japanese, Oral presentation
    [Domestic Conference]
  • 全学放射線管理システムの更新とeラーニングによる教育訓練の試み
    野矢洋一; 安井博宣; 阿保憲史; 久保直樹; 東川桂; 久下裕司
    日本放射線安全管理学会第16回学術大会, 28 Jun. 2017, Japanese, Poster presentation
    [Domestic Conference]
  • ホットセルに格納可能な小型RIガス貯留装置の開発
    阿保憲史; 野矢洋一; 東川桂; 安井博宣; 久下裕司
    日本放射線安全管理学会第16回学術大会, 28 Jun. 2017, Japanese, Oral presentation
    [Domestic Conference]
  • Accumulation mechanism of novel PET imaging probe “[18F]DiFA” in hypoxic cells revealed by imaging mass spectrometry.
    Shimizu Y; Zhao S; Kishi R; Yasui H; Nishijima K; Matsumoto H; Tamaki N; Ogawa M; Kuge Y
    SNMMI 2017 Annual Meeting, 10 Jun. 2017, English, Oral presentation
    [International presentation]
  • Preclinical evaluation of [18F]DiFA, a novel PET probe for tumor hypoxia, in comparison with [18F]MISO.
    Yasui H; Zhao S; Higashikawa K; Ukon N; Shimizu Y; Matsumoto H; Tamaki N; Kuge Y
    SNMMI 2017 Annual Meeting, 10 Jun. 2017, English, Poster presentation
    [International presentation]
  • 18F -MISOとの比較による新規低酸素標的PETプローブ18F -DiFAの有用性評価
    安井博宣; 趙松吉; 東川桂; 右近直之; 志水陽一; 松本博樹; 玉木長良; 久下裕司
    第12 回日本分子イメージング学会総会・学術集会, 25 May 2017, Japanese, Oral presentation
    [Invited], [Domestic Conference]
  • 新規低酸素標的PETプローブ18F -DiFAの有効性評価を目的とした腫瘍集積能および腫瘍内代謝物の解析
    安井博宣; 志水陽一; 趙松吉; 東川桂; 右近直之; 岸伶美; 西嶋剣一; 松本博樹; 小川美香子; 玉木長良; 久下裕司
    第二回北大部局横断シンポジウム, 14 Mar. 2017, Japanese, Poster presentation
    [Domestic Conference]
  • Noninvasive imaging of cycling hypoxia to improve cancer therapy
    Yasui H
    CIS WORKSHOP 2017, 27 Jan. 2017, English, Nominated symposium
    [Invited], [Domestic Conference]
  • ホットセルに格納可能な小型RIガス貯留装置の開発
    阿保憲史; 野矢洋一; 東川桂; 安井博宣; 久下 裕司
    日本放射線安全管理学会第15回学術大会, 30 Nov. 2016, Japanese, Oral presentation
    岡山大学 (岡山市, 岡山), [Domestic Conference]
  • “腫瘍内酸素イメージングのための同位体標識ニトロキシルラジカル混合溶液の特性評価
    久保田晴江; 安井博宣; 松元慎吾; 稲波修; Kirilyuk I.A; Khramtsov V.V; 平田拓
    第55回電子スピンサイエンス学会年会, 12 Nov. 2016, Japanese, Oral presentation
    大阪市立大学 (大阪市, 大阪), [Domestic Conference]
  • 親脂質性Tetraphenylphosphonium誘導体は放射線によるがん細胞の致死作用を増強する
    稲波修; 安井博宣; 西村英里; 山本久美子; 鈴木基史; 酒井友里; 房知輝; 山盛徹; 山崎俊栄; 山田健一
    第55回電子スピンサイエンス学会年会, 12 Nov. 2016, Japanese, Oral presentation
    大阪市立大学 (大阪市, 大阪), [Domestic Conference]
  • X線照射後のヒト子宮頸がん由来HeLa細胞におけるセミキノンラジカルおよびFe-SクラスターのESRによる評価
    山本久美子; 池中良徳; 一瀬貴大; 石塚真由美; 安井博宣; 鵜飼光子; 山盛徹; 稲波修
    第55回電子スピンサイエンス学会年会, 11 Nov. 2016, Japanese, Poster presentation
    大阪市立大学 (大阪市, 大阪), [Domestic Conference]
  • HeLa細胞における放射線照射後のミトコンドリアのセミキノンラジカルとFe-Sクラスターの電子スピン共鳴法による評価
    稲波修; 山本久美子; 房知輝; 酒井友里; 鈴木基史; 平岡和佳子; 安井博宣; 山盛徹
    日本放射線影響学会第59回大会, 27 Oct. 2016, Japanese, Oral presentation
    JMSアステールプラザ (広島市, 広島), [Domestic Conference]
  • がん細胞の放射線応答における転写調節因子Id1の役割
    安井博宣; 竹内麻依; 山盛徹; 松本英樹; 高橋昭久; 稲波修
    日本放射線影響学会第59回大会, 27 Oct. 2016, Japanese, Oral presentation
    JMSアステールプラザ (広島市, 広島), [Domestic Conference]
  • Comparative assessment of hypoxic radiosensitizing properties of glycididazole and doranidazole in vitro and in vivo
    Yasui H; Kubota N; Yamamori T; Inanami O
    62th Annual International Meeting Radiation Research Society, 17 Oct. 2016, English, Poster presentation
    Hilton Waikoloa Village (Waikoloa Village, HI), [International presentation]
  • CW-EPR-based oxygen mapping technique using a pair of isotopic nitroxyl radicals
    Kubota H; Komarov D.A; Yasui H; Matsumoto S; Inanami O; Kirilyuk I.A; Khramtsov V.V; Hirata H
    10th International Workshop on EPR in Biology and Medicine, 04 Oct. 2016, English, Oral presentation
    International Cultural Centre (Krakow, Poland), [International presentation]
  • 新規低酸素イメージング剤“18F-DiFA”の腫瘍集積能・腫瘍内代謝物評価
    志水陽一; 趙松吉; 岸伶美; 安井博宣; 西嶋剣一; 松本博樹; 玉木長良; 小川美香子; 久下裕司
    第16回放射性医薬品・画像診断薬研究会, 01 Oct. 2016, Japanese, Oral presentation
    みやこめっせ (京都市,京都), [Domestic Conference]
  • 新規低酸素標的PETプローブ18F -DiFAの有効性評価のための18F -MISOとの比較検討
    安井博宣; 趙松吉; 東川桂; 右近直之; 志水陽一; 松本博樹; 玉木長良; 久下裕司
    第16回放射性医薬品・画像診断薬研究会, 01 Oct. 2016, Japanese, Oral presentation
    みやこめっせ (京都市,京都), [Domestic Conference]
  • X線照射したヒト子宮頸がん由来HeLa細胞におけるミトコンドリア機能を中心としたエネルギー代謝応答の解析
    山本久美子; 池中良徳; 一瀬貴大; 石塚真由美; 安井博宣; 鵜飼光子; 山盛徹; 稲波修
    第159 回日本獣医学会学術集会, 07 Sep. 2016, Japanese, Oral presentation
    日本大学 (藤沢市, 神奈川), [Domestic Conference]
  • ヒト子宮頸部がんHeLa細胞における放射線照射後のミトコンドリア応答
    山本久美子; 池中良徳; 一瀬貴大; 安井博宣; 鵜飼光子; 山盛徹; 稲波修
    第69 回日本酸化ストレス学会学術集会, 30 Aug. 2016, Japanese, Poster presentation
    仙台国際センター (仙台市, 宮城), [Domestic Conference]
  • Development of a CW-EPR-based oxygen-mapping technique using a pair of isotopic nitroxyl radicals
    Hirata H; Kubota H; Yasui H; Matsumoto S; Inanami O; Kirilyuk I.A; Khramtsov V.V
    Asia-Pacific EPR/ESR Symposium 2016, 29 Aug. 2016, English, Oral presentation
    Mayak Hotel (Irkutsk, Russia), [International presentation]
  • FMISO PETイメージングによるeribulinの腫瘍内低酸素状態解除作用の実証―小動物用PETと乳癌モデルを用いた検討―
    趙松吉; 于聞文; 右近直之; 西嶋剣一; 志水陽一; 東川桂; 安井博宣; 山下啓子; 玉木長良; 久下裕司
    第12回小動物インビボイメージング研究会, 30 Jul. 2016, Japanese, Oral presentation
    福島県立医科大学 (福島市,福島), [Domestic Conference]
  • Characteristics of 14N- and 15N-labeled dicarboxy-PROXYLs as oxygen-sensitive probes for CW-EPR-based single-point imaging (SPI)
    Kubota H; Yasui H; Matsumoto S; Inanami O; Kirilyuk I.A; Khramtsov V.V; Hirata H
    58th Annual Rocky Mountain Conference on Magnetic Resonance (39th International EPR Symposium), 19 Jul. 2016, English, Oral presentation
    Beaver Run Resort & Conference Center (Breckenridge, CO), [International presentation]
  • Feasibility study of a CW-EPR-based oxygen mapping technique using a pair of isotopic nitroxyl radicals
    Hirata H; Kubota H; Yasui H; Matsumoto S; Inanami O; Kirilyuk I.A; Khramtsov V.V
    58th Annual Rocky Mountain Conference on Magnetic Resonance (39th International EPR Symposium), 19 Jul. 2016, English, Oral presentation
    Beaver Run Resort & Conference Center (Breckenridge, CO), [International presentation]
  • ヒト子宮頸部がんHeLa細胞における放射線照射後のエネルギー産生とその意義
    稲波修; 山本久美子; 西村英里; 房知輝; 酒井友里; 鈴木基史; 池中良徳; 一瀬貴大; 石塚真由美; 安井博宣; 鵜飼光子; 山田健一; 山崎俊栄; 山盛徹
    第54回日本放射線腫瘍学会生物部会学術大会, 16 Jul. 2016, Japanese, Oral presentation
    I-site なんば (大阪市,大阪), [Domestic Conference]
  • X線照射後のミトコンドリア形態変化が細胞の放射線応答に与える役割
    山盛徹; 池悟志; 房知輝; 市居修; 笹川朋哉; 安井博宣; 稲波修
    第二回北大部局横断シンポジウム, 07 Mar. 2016, Japanese, Poster presentation
    北海道大学 (札幌市, 北海道), [Domestic Conference]
  • 電子スピン共鳴イメージングによるがん代謝標的薬剤と放射線併用治療の最適化
    安井博宣; 齋藤圭太; 松元慎吾; 山盛徹; Krishna MC; 稲波修
    第二回北大部局横断シンポジウム, 07 Mar. 2016, Japanese, Poster presentation
    北海道大学 (札幌市, 北海道), [Domestic Conference]
  • がん治療のための新規放射線増感剤の開発
    稲波修; 安井博宣; 山盛徹; 山田健一; 白土博樹; 松田彰
    第二回北大部局横断シンポジウム, 07 Mar. 2016, Japanese, Poster presentation
    北海道大学 (札幌市, 北海道), [Domestic Conference]
  • EPR imaging (pO2)
    安井博宣
    第6回放射線生物学セミナー, 20 Feb. 2016, Japanese, Public discourse
    名古屋市立大学 (名古屋市, 愛知), [Invited], [Domestic Conference]
  • 非侵襲イメージングに基づくin vivo微小環境を標的とした放射線増感治療の可能性
    安井博宣; 齋藤圭太; 松元慎吾; 山盛徹; Krishna MC; 稲波修
    第18回癌治療増感研究シンポジウム, 05 Feb. 2016, Japanese, Nominated symposium
    奈良県文化会館 (奈良市, 奈良), [Invited], [Domestic Conference]
  • Application of electron spin resonance (ESR) pO2 imaging to improve tumor radiotherapy
    Yasui H; Krishna M.C; Inanami O
    18th Seoul National University-Hokkaido University Joint Symposium, 27 Nov. 2015, English, Oral presentation
    Seoul University (Seoul, Korea), [Invited], [International presentation]
  • ESR based imaging biomarkers to guide treatment in tumor bearing mice
    Matsumoto S; Saito K; Kishimoto Shun; Takakusagi Y; Yasui H; Matsuo M; Krishna M.C
    第54回電子スピンサイエンス学会年会, 04 Nov. 2015, Japanese, Oral presentation
    朱鷺メッセ (新潟市, 新潟), [Domestic Conference]
  • 酸素感受性同位体ニトロキシルラジカルの特性評価実験
    久保田晴江; 安井博宣; 松元慎吾; 三宅祐輔; 稲波修; Kirilyuk I.A; Khramtsov V.V; 平田拓
    第54回電子スピンサイエンス学会年会, 04 Nov. 2015, Japanese, Poster presentation
    朱鷺メッセ (新潟市, 新潟), [Domestic Conference]
  • 電子スピン共鳴法を用いたがんの生理機能と放射線応答機構の解明に向けた研究
    安井博宣
    第54回電子スピンサイエンス学会年会, 03 Nov. 2015, Japanese, Invited oral presentation
    朱鷺メッセ (新潟市, 新潟), [Invited], [Domestic Conference]
  • X線照射したがん細胞のESRオキシメトリーを用いた酸素消費率を指標としたミトコンドリア機能の解析
    山本久美子; 安井博宣; 山盛徹; 中村秀夫; 鵜飼光子; 稲波修
    第54回電子スピンサイエンス学会年会, 03 Nov. 2015, Japanese, Poster presentation
    朱鷺メッセ (新潟市, 新潟), [Domestic Conference]
  • 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl) cytosine (ECyd)併用による陽子線増感治療の実現に向けた基礎研究
    前田憲一郎; 安井博宣; 山盛徹; 松浦妙子; 高尾聖心; 鈴木基史; 松田彰; 稲波修; 白土博樹
    第1回放射線ワークショップ, 16 Oct. 2015, Japanese, Oral presentation
    富山大学 (富山市, 富山), [Domestic Conference]
  • ミトコンドリア指向性化合物における分子骨格と放射線増感作用との相関性に関する研究
    安井博宣; 西村英里; 山盛徹; 山本久美子; 山崎俊栄; 山田健一; 稲波修
    第1回放射線ワークショップ, 16 Oct. 2015, Japanese, Oral presentation
    富山大学 (富山市, 富山), [Domestic Conference]
  • 転写調節因子Id1ノックダウンが放射線感受性に与える影響とそのメカニズムの解明
    竹内麻依; 安井博宣; 鈴木基史; 酒井友里; 山盛徹; 稲波修
    第158回日本獣医学会学術総会, 08 Sep. 2015, Japanese, Oral presentation
    北里大学 (十和田市, 青森), [Domestic Conference]
  • 放射線照射後のミトコンドリア分裂におけるDrp1リン酸化の意義
    房知輝; 山盛徹; 池悟志; 鈴木基史; 酒井友里; 安井博宣; 稲波修
    第158回日本獣医学会学術総会, 08 Sep. 2015, Japanese, Oral presentation
    北里大学 (十和田市, 青森), [Domestic Conference]
  • MPS1を介したスピンドル形成チェックポイントが哺乳動物細胞の放射線/化学療法剤感受性に与える影響の解析
    鈴木基史; 山盛徹; 安井博宣; 稲波修
    第158回日本獣医学会学術総会, 08 Sep. 2015, Japanese, Oral presentation
    北里大学 (十和田市, 青森), [Domestic Conference]
  • がん代謝標的薬剤ジクロロ酢酸処理後の腫瘍内酸素環境の経時的解析と放射線併用プロトコールの最適化
    安井博宣; 齋藤圭太; 西田直哉; 松元慎吾; 山盛徹; Murali C. Krishna; 稲波修
    若手放射線生物学研究会2015年度専門研究会, 08 Aug. 2015, Japanese, Oral presentation
    東京医科歯科大学 (文京区, 東京), [Domestic Conference]
  • 酸素バイオロジーと磁気共鳴
    安井博宣
    第13回ESR夏の学校, 21 Jul. 2015, Japanese, Public discourse
    温泉旅館「千鶴」 (湯河原町, 神奈川県), [Invited], [Domestic Conference]
  • 親脂質性triphenylphosphonium(TPP)化合物によるがん細胞における放射線増感作用
    稲波修; 安井博宣; 西村英里; 永根大幹; 笹川朋哉; 山盛徹; 山崎俊栄; 山田健一
    第68 回日本酸化ストレス学会学術集会, 11 Jun. 2015, Japanese, Oral presentation
    かごしま県民交流センター (鹿児島市, 鹿児島), [Domestic Conference]
  • The Relationship between Radiation-induced Cell Cycle Arrest and Reactive Oxygen Species Production from Mitochondria
    Yamamori T; Yasui H; Inanami O
    15th International Congress of Radiation Research, 25 May 2015, English, Nominated symposium
    Kyoto International Conference Center (Kyoto), [International presentation]
  • Inhibition of The Mitochondrial Fission Protein Dynamin-related Protein 1 Impairs Mitotic Catastrophe After X-irradiation
    Yamamori T; Ike S; Bo T; Sasagawa T; Suzuki M; Sakai Y; Yasui H; Inanami O
    15th International Congress of Radiation Research, 25 May 2015, English, Poster presentation
    Kyoto International Conference Center (Kyoto), [International presentation]
  • Drp1 Phosphorylation at Ser616 but Not Ser637 Is Required for Radiation-Induced Mitochondrial Fission
    Bo T; Yamamori T; Ike S; Suzuki M; Yasui H; Inanami O
    15th International Congress of Radiation Research, 25 May 2015, English, Poster presentation
    Kyoto International Conference Center (Kyoto), [International presentation]
  • A Feasibility Study for the Establishment of Proton Therapy Combined with 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl) Cytosine (ECyd)
    Maeda K; Yasui H; Matsuura T; Yamamori T; Takao S; Suzuki M; Matsuda A; Inanami O; Shirato H
    15th International Congress of Radiation Research, 25 May 2015, English, Poster presentation
    Kyoto International Conference Center (Kyoto), [International presentation]
  • MPS1 Inhibitors Enhance Chemosensitivity to Etoposide and Paclitaxel but Not Radiosensitivity in Murine SCCVII Cells
    Suzuki M; Yamamori T; Yasui H; Inanami O
    15th International Congress of Radiation Research, 25 May 2015, English, Poster presentation
    Kyoto International Conference Center (Kyoto), [International presentation]
  • Radiosensitizing Effect by Mitochondria-targeted Nitroxides in Tumor Cells
    Inanami O; Yasui H; Nishimura E; Nagane M; Sasagawa T; Yamamori T; Yamasaki T; Yamada K
    15th International Congress of Radiation Research, 25 May 2015, English, Poster presentation
    Kyoto International Conference Center (Kyoto), [International presentation]
  • The Effect of Intermittent Hypoxia on the Cellular Sensitivities to X-irradiation and to Boron Neutron Capture Reaction in Rat Glioma Cells
    Yasui H; Nagane M; Yamamori T; Hirayama R; Kondo N; Masunaga SI; Inanami O
    15th International Congress of Radiation Research, 25 May 2015, English, Poster presentation
    Kyoto International Conference Center (Kyoto), [International presentation]
  • ミトコンドリア指向性ニトロキシドにおける分子骨格と放射線増感作用との相関性に関する研究
    安井博宣; 西村英里; 永根大幹; 笹川朋哉; 山盛徹; 山崎俊栄; 山田健一; 稲波修
    第17回癌治療増感研究シンポジウム, 06 Feb. 2015, Japanese, Oral presentation
    奈良県文化会館 (奈良市, 奈良), [Domestic Conference]
■ Syllabus
  • プレクリニカル実習, 2024年, 学士課程, 獣医学部
  • 放射線生物学演習, 2024年, 博士後期課程, 獣医学院
  • 汎動物科学特論, 2024年, 博士後期課程, 獣医学院
  • 環境獣医科学特論, 2024年, 博士後期課程, 獣医学院
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
  • 放射線生物学, 2024年, 学士課程, 獣医学部
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
  • 放射線獣医療・画像診断学, 2024年, 学士課程, 獣医学部
  • 放射線生物学演習, 2024年, 学士課程, 獣医学部
  • 生物学Ⅱ, 2024年, 学士課程, 全学教育
■ Affiliated academic society
  • THE JAPANESE CANCER ASSOCIATION
  • INTERNATIONAL ASSOCIATION FOR THE SENSITIZATION OF CANCER TREATMENT
  • THE SOCIETY OF ELECTRON SPIN SCIENCE AND TECHNOLOGY
  • SOCIETY FOR FREE RADICAL RESEARCH JAPAN
  • THE JAPAN RADIATION RESEARCH SOCIETY
  • THE JAPANESE SOCIETY OF VETERINARY SCIENCE
  • Japan Radioisotope Association
  • Japanese Society for Radiation Oncology
■ Research Themes
  • 生体金属レドックスとがん特異的代謝への介入による放射線誘発細胞死の動態解析と制御
    科学研究費助成事業
    01 Apr. 2025 - 31 Mar. 2028
    安井 博宣
    日本学術振興会, 基盤研究(B), 北海道大学, 25K03260
  • Prediction and assessment of ferroptosis-inducing cancer therapy using a novel PET probe targeting Tf-receptor
    Grants-in-Aid for Scientific Research
    Apr. 2025 - Mar. 2028
    久下 裕司; 安井 博宣; 竹中 淳規; 水野 雄貴
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 25K10927
  • Development of PET/EPR functional imaging method for early diagnosis of cancer
    Grants-in-Aid for Scientific Research
    01 Apr. 2024 - 31 Mar. 2027
    藤井 博匡; 久下 裕司; 安井 博宣; 赤羽 英夫
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Health Sciences University of Hokkaido, 24K10558
  • Development of a New Dosimetry Technique Using Air Dose Rates for Nuclear Medicine Theranostics
    Grants-in-Aid for Scientific Research
    01 Apr. 2024 - 31 Mar. 2027
    渡邊 史郎; 安井 博宣; 水野 雄貴
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 24K10753
  • 多価効果と代謝性リンカーの融合による革新的核医学治療薬の開発
    科学研究費助成事業
    Apr. 2022 - Mar. 2027
    水野 雄貴; 上原 知也; 安井 博宣; 西嶋 剣一
    がんを標的とした核医学治療の実用化が世界中で加速している。特に、α線放出RIを用いた核医学治療は、がん細胞への傷害性の高さから大きな注目を集めている。本研究では、核医学治療の成功に欠かせない、高い腫瘍集積と低い正常組織集積を兼ね備えたRI標識薬剤の開発を目指す。具体的には、多価効果を用いた標的への集積向上を目指した薬剤設計と、代謝性リンカーを用いた正常組織への集積低減を目指した薬剤設計を融合し、革新的核医学治療薬剤の開発を行う。
    令和5年度は、細胞表面の複数のintegrin αvβ3と同時結合可能な125I-IB-4価RGDの構造を母体とし、代謝性リンカーとしてGly-Lys (GK) を導入した125I-IB-GK-4価RGDを作製した。作製した125I-IB-GK-4価RGDをU87MG皮下移植マウスに投与し、放射能の生体内分布を経時的に評価した。その結果、125I-IB-GK-4価RGDの腎臓への集積は125I-IB-4価RGDと比べて大幅に減少し、代謝性リンカーが期待通り開裂したことが示唆された。一方、その腫瘍集積も125I-IB-4価RGDと比べて低値を示し、腫瘍組織においても代謝性リンカーが開裂したことが示唆された。結果として、125I-IB-GK-4価RGDの腫瘍/腎臓比は、代謝性リンカーを持たない125I-IB-4価RGDと同程度であった。
    一方、今年度は211At標識4価RGDの合成を実施した。放射化学的収率は13%とやや低値であったが、放射化学的純度は99%以上であった。作製した211At-AB-GK-4価RGDは生理食塩水中において3時間後も安定に存在し、また、U87MGを用いたin vitro実験において、211At-AB-GK-4価RGDはintegrin αvβ3特異的な高い集積を示した。
    日本学術振興会, 基盤研究(B), 北海道大学, 23K24268
  • 多価効果と代謝性リンカーの融合による革新的核医学治療薬の開発
    科学研究費助成事業 基盤研究(B)
    Apr. 2022 - Mar. 2027
    水野 雄貴; 上原 知也; 安井 博宣; 西嶋 剣一
    がんを標的とした核医学治療の実用化が世界中で加速している。特に、α線放出RIを用いた核医学治療は、がん細胞への傷害性の高さから大きな注目を集めている。本研究では、核医学治療の成功に欠かせない、高い腫瘍集積と低い正常組織集積を兼ね備えたRI標識薬剤の開発を目指す。具体的には、多価効果を用いた標的への集積向上を目指した薬剤設計と、代謝性リンカーを用いた正常組織への集積低減を目指した薬剤設計を融合し、革新的核医学治療薬剤の開発を行う。
    令和4年度は、当初利用を計画していた多価c(RGDfK) の足場分子構造について、見直しを行った。具体的には、グルタミン酸を足場分子として2つのc(RGDfK) を導入した化合物をリガンドとして利用することを計画していたが、より優れた腫瘍集積性と滞留性を期待し、足場分子Xに 4つのc(RGDfK) を導入した4価RGDを新たに合成した。Integrin αvβ3陽性細胞としてU87MGとMDA-MB-435Sを用いて4価RGDの評価を行った結果、4価RGDはどちらの細胞株においても非常に高い細胞集積性と滞留性を示した。一方、ある多価化合物が複数の標的分子と同時結合可能かどうかは、競合剤存在下で解離速度が増加するかで判断することができる。そこで、4価RGDのU87MGとMDA-MB-435Sからの解離速度を、競合剤存在下と非存在下で比較した。その結果、4価RGDの解離速度は競合剤存在下で著しく増加し、どちらの細胞株においても4価RGDが複数のintegrin αvβ3と同時結合できていることが示された。また、U87MGを皮下移植したマウスを用いたex vivo体内動態試験の結果、4価RGDは優れた腫瘍集積性と滞留性を示し、投与24時間後においても、投与1時間後における腫瘍集積量の約80%の放射能が腫瘍に残存していた。
    日本学術振興会, 基盤研究(B), 北海道大学, 22H03007
  • Research for local control and high accuracy of cancer senolytic therapy by non-invasive imaging
    Grants-in-Aid for Scientific Research
    30 Jun. 2023 - 31 Mar. 2026
    安井 博宣
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Hokkaido University, 23K18259
  • 内因性抗酸化物質を指標とした非侵襲な脳内酸化ストレス状態定量的評価手法の新規構築
    科学研究費助成事業
    01 Apr. 2023 - 31 Mar. 2026
    榎本 彩乃; 安井 博宣
    日本学術振興会, 基盤研究(B), 長崎国際大学, 23H03728
  • Oxygen and pH imaging of malignant tumors using electron paramagnetic resonance
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    01 Apr. 2022 - 31 Mar. 2026
    平田 拓; 安井 博宣
    腫瘍モデルマウスの酸素分圧およびpHイメージングを実施するための要素技術として、スペクトル空間イメージング法がある。このイメージング法は、各位置(三次元画像では各ボクセル)における電子スピン共鳴の一次微分吸収スペクトルを再構成する計測法である。電子スピンのスペクトル情報から酸素分圧やpHの値を推定し、それらの情報を三次元データとして可視化する。
    本研究課題では、腫瘍モデルマウスの酸素分圧と細胞外pHの複合イメージングを実現するために、(i)計測感度の向上、(ii) 4次元データの代数的逐次近似再構成(ART)法の高速アルゴリズムの検討と実装、(iii) 磁気共鳴イメージング(MRI)による形態画像との酸素分圧およびpH画像の重ね合わせ、を目標とした。
    (i) 計測感度向上(信号対雑音比SNR)については、受信システムの雑音特性を明らかにするためにノイズの電力密度特性を取得した。また、フーリエ領域において雑音が電子スピン共鳴のスペクトル情報(高調波)をマスキングする次数を明らかにした。
    (ii) 3次元および4次元のスペクトル空間イメージングを行うために、ART法による画像再構成アルゴリズムのFortran 95による実装とOpenMPによる並列化を行った。その結果、64x64x64の3次元空間と768点のスペクトル情報で構成される4次元スペクトル空間データの再構成計算をできるようにした。
    (iii) 研究代表者の研究室に 1テスラ・マウス用MRI(Aspect Imaging、M3)を導入(リース)し、腫瘍モデルマウスの形態画像を取得できるようにした。酸素分圧およびpH画像との重ね合わせはまだ未実施であるが、導入したMRIにおいて腫瘍モデルマウスのルーチン計測を行う手技を獲得した。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 22H00200
  • 内因性抗酸化物質を指標とした非侵襲な脳内酸化ストレス状態定量的評価手法の新規構築
    科学研究費助成事業
    Apr. 2023 - Mar. 2026
    榎本 彩乃; 安井 博宣; 麻生 沙和
    日本学術振興会, 基盤研究(B), 長崎国際大学, 23K28417
  • 生体金属ホメオスタシスの破綻による細胞死誘導の時空間動態解析と放射線治療への展開
    科学研究費助成事業
    28 Feb. 2024 - 31 Mar. 2025
    安井 博宣
    日本学術振興会, 基盤研究(B), 北海道大学, 23K24994
  • Spatio-temporal dynamics analysis of cell death induction due to disruption of biometal homeostasis and its application to radiotherapy
    Grants-in-Aid for Scientific Research
    01 Apr. 2022 - 31 Mar. 2025
    安井 博宣
    本研究では、「正常細胞とがん細胞におけるX線照射後の遷移金属や関連因子の動態がレドックス状態や細胞死にどのような影響を与えるのか?また、イメージング等検出技術によってそのメカニズムを解明することで、生体金属の恒常性破綻をがん放射線治療のアプローチとすることが可能か?」という問いに対し、初年度では(1)X線照射による遷移金属や関連因子の動態と細胞死誘導の評価と作用点を探索することおよび(2)増感標的となる分子の決定と実験的治療検討をin vitroで行うことを目的とした。研究成果として、昨年報告された銅によって引きおこされる新しい細胞死について放射線作用との関係を調べるために、銅イオノフォアであるElesclomolを用いて、HCT116細胞やMIA-Paca-2細胞においてピルビン酸デヒドロゲナーゼキナーゼ阻害剤ジクロロ酢酸(DCA)や乳酸脱水素酵素阻害剤FX11と併用した際のElesclomolの細胞毒性の増強作用の有無について調べた。その結果、既報ではあるがDCAのElesclomolの増強作用が確認できたことに加えて、FX11においてもElesclomolの細胞毒性の増強作用を有することがコロニー形成法によって明らかとなった。各種阻害剤を用いることで、この増感作用が、アポトーシス、ネクロプトーシス、フェロトーシスではなく、銅キレート剤や抗酸化剤によって抑制されたことから、銅に関連する酸化ストレスによる細胞死に依存していることが明らかとなった。以上の結果から、銅代謝に介入することが放射線感受性を引き上げることに繋がることが示唆された。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 22H03740
  • PET imaging for cancer treatment inducing ferrotosis
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2021 - 31 Mar. 2025
    久下 裕司; 安井 博宣; 小川 美香子; 平田 健司; 水野 雄貴
    近年、フェロトーシスと呼ばれる新しい細胞死様式が報告され、フェロトーシスを誘導する薬剤が新たながん治療薬として注目されている。このフェロトーシスの進行には、トランスフェリン受容体1 (TfR1) が深く関与することが知られている。本研究の目的は、TfR1の特異的イメージングを可能とする新たなPETイメージング剤を合成し、PETによるTfR1イメージングがフェロトーシス誘導剤の治療効果予測/判定やフェロトーシス誘導剤の開発に有効な手段となるか否かを明らかにすることにある。
    本目的達成のため、これまでに主に新たなPETイメージング剤の合成検討、及びIn vitro細胞実験を行った。その結果、TfR1への親和性を有する7残基直鎖ペプチド (DT7) を母体とした68Ga標識プローブ(68Ga-DT7)が、T98G (TfR1高発現細胞株) に対してTfR1特異的に集積することを見出した。一方で、その集積量はやや低かったことから、分子内に2つのDT7ペプチドを有する2価DT7を新たに設計し、合成に成功した。しかし、68Gaで標識した2価DT7のT98Gへの集積量は予想に反して低かった。さらに、直鎖上のDT7ペプチドを環状化した環化ペプチドを合成し、T98Gへの集積量を評価したが、TfR1特異的集積量の向上には繋がらなかった。
    上記検討結果から、TfR1への親和性がより高いリガンドを母体としたプローブを開発する必要性が示唆された。そこで、cystine dense peptideの1種でありTfR1との高い結合親和性を有するTfRB1G3を母体としたプローブの開発を開始した。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 21H02858
  • Targetting of cancer-specific metabolic system for senolytic therapy
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    01 Apr. 2020 - 31 Mar. 2025
    稲波 修; 平岡 和佳子; 岡松 優子; 安井 博宣; 滝口 満喜; 平田 拓
    本年度はインビトロの培養細胞の系の実験で、以下の四つの結果が明らかとなった。
    1)グルタミン要求性の強いヒト肺がんA549細胞やH460細胞では、放射線照射により、これらの細胞でのグルタミンの取り込みの増大とグルタメートの増大、すなわちグルタミナーゼの活性化を起こす事を明らかにした。さらに、グルタミン代謝阻害剤添加あるいはグルタミン欠乏培地下で培養すると治療線量レベルの放射線照射によって多くの老化様細胞死とSASPの培養液中への分泌を増強させることが可能である事が明らかとなった。
    2)グルタミノリシス阻害条件下で放射線による老化様細胞死の誘発機構には活性酸素種の生成量、グルタチオン量の変化DNA損傷の量、さらにはDNA損傷に伴う伴うp53やp21、p16の発現変化などの既知のメカニズムの関与は殆ど無く、未知の機構の関与が示唆されている。
    3)更にグルタミノリシス阻害条件下で放射線誘発する老化様細胞死を起こす条件で、Bcl-XL阻害剤ABT-737によって、この増大した老化様細胞死の多くはアポトーシスに変換できること、いわゆるセノリシスを起こせることを明らかにした。
    4)一方では、同じ肺がん由来細胞でも786-o細胞ではグルタミン代謝阻害が老化様細胞の増強を起こさず、A549やH460細胞と同様の現象は観察されず、全ての肺がん細胞に於いて同様の機構が働いていない事も明らかとなった。また、脂質代謝阻害剤は老化様細胞増強には関与しなかった。
    以上の結果はグルタミン要求性の強い肺がん細胞を中心にその亜致死レベルのグルタミノリシス阻害条件下で治療線量レベルの放射線照射をすると、多量の老化様細胞死の増大が起こす事を示しており、さらに、アポトーシス抑制因子の阻害剤で効率よく老化様細胞死をアポトーシスに変換できることが明確になった。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 20H00443
  • PET imaging for cancer treatment inducing ferrotosis
    Grants-in-Aid for Scientific Research
    Apr. 2021 - Mar. 2025
    久下 裕司; 安井 博宣; 小川 美香子; 平田 健司; 水野 雄貴
    近年、フェロトーシスと呼ばれる新しい細胞死の様式が報告され、フェロトーシスを誘導する薬剤が新たながん治療薬として注目されている。このフェロトーシスの進行には、トランスフェリン受容体1 (TfR1) が深く関与することが知られている。そこで本研究では、TfR1を標的とした新たなPETイメージング剤を開発し、フェロトーシス誘導剤の治療効果予測/判定に有効なイメージング技術を確立することを目的とする。
    令和5年度は昨年度に引き続き、cystine dense peptideの1種であるTfRB1G3を母体としたPETイメージング剤の開発を進めた。TfRB1G3にHBED-CC (ガリウムに対するキレート試薬) を縮合した標識前駆体を合成し、67/68Ga標識体を作製した。作製した67Ga標識体を用いてsaturation binding assayを実施したところ、そのKD値は1.6 nMであり、TfR1への非常に高い親和性を示した。また、67Ga標識TfRB1G3をマウス血漿中で1時間インキュベートした後、HPLCを用いてその未変化体比率を評価したところ、90%以上の放射能が未変化体として存在し、生体内における高い安定性が示唆された。さらに、皮下腫瘍移植マウスを用いた体内分布試験を実施した結果、67Ga標識TfRB1G3はTfR1陽性腫瘍への高い集積 (8.6 %ID/g) を示し、その集積は過剰のTfRB1G3の同時投与で1.6 %ID/gまで減少した。これらの結果から、67/68Ga標識TfRB1G3がTfR1発現量を特異的かつ高感度に画像化する核医学イメージング剤として、有望な性質を有していることが示唆された。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K21417
  • Ferroptosis imaging with PET: Challenge to assess vulnerability of atherosclerotic plaques
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)
    09 Jul. 2021 - 31 Mar. 2024
    久下 裕司; 安井 博宣; 小川 美香子; 横田 千晶; 水野 雄貴
    動脈硬化病変の評価においては、早期治療を必要とする“破綻しやすいプラーク(不安定プラーク)”を的確に診断することが重要である。最近、鉄依存性酸化ストレスに起因するフェロトーシスと呼ばれる細胞死の様式が、動脈硬化の病態にも深く関与していることが報告された。本研究の目的は、フェロトーシス関連分子のPETイメージングにより、不安定プラークの診断が可能となるか検証することにある。
    フェロトーシスの進行には、トランスフェリン受容体1 (TfR1) が深く関与することが知られている。令和3年度は、TfR1への高い結合親和性を有する直鎖ペプチド (DT7) を母体とした68Ga標識プローブ(68Ga-DT7)を合成し、in vitro実験条件下でTfR1イメージング剤としての有用性を評価した。その結果、68Ga-DT7は、TfR1特異的に集積したが、細胞集積量は十分ではなかった。そこで、細胞集積量の向上を目指してペプチドの多量体化や環状化などを実施したが、68Ga-DT7の細胞集積量を上回る誘導体の創成には至らなかった。
    一方、不安定プラークにおけるフェロトーシスの関与をより多角的に評価するため、プラークにおける酸化ストレスを可視化できるプローブの合成と評価を開始した。合成した標識体は活性酸素種 (ROS)との反応によって錯体が崩壊し、酸化ストレスイメージング剤として機能する可能性が示された。
    以上の検討結果から、TfR1への結合親和性がより高いリガンドの68Ga標識体を作製する必要性が示唆された。今後、cystine dense peptideの1種であるTfRB1G3の68Ga標識体を合成し、TfR1イメージング剤としての評価を行う。また、フェロトーシス関連分子のイメージングによる不安定プラークの多角的評価に向けて、酸化ストレスイメージング剤の開発も継続する。
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Hokkaido University, 21K19433
  • Development of a novel ESR oximetry for tumor-therapy-effect prediction
    Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
    27 Oct. 2020 - 31 Mar. 2024
    稲波 修; 安井 博宣; 永根 大幹; 山下 匡
    コロナ禍が続く状況で測定を予定していた米国ダートマスへの渡航が困難を極める中、これを打開するために、昨年度は小型の750MHz可搬型ESRイメージング装置を開発、実用化を進めている大阪大学の赤羽准教授ならびに北海道医療大学の藤井博匡教授に参画して頂き、2台の装置を北大と麻布大に設置して本プロジェクトの推進を行った。同時にOxychipの評価についてはZOOMを用いてKuppusamy研究室とコミュニケーションをとりながら進める体制を確立した。
    低酸素性細胞検出のためのOxychipの実用化についてはポリヒドロキシ酪酸など増感剤を用いて検討を実施した。加えて、上記の可搬型ESR装置の予備的検討として、移植腫瘍モデルにおいてOxychipとの組合せにより組織酸素分圧の測定を試み、実用可能であることを示した。またこの装置とOxychipの更なるアプリケーションを開拓するため、マウスに測定部にOxychipを移植し、大体静脈結紮による下肢虚血モデルを作成し検討したところ、虚血に伴う組織酸素分圧の低下や組織修復・血管新生に伴う酸素分圧の回復過程の観察が可能である事を明らかにした。
    また、固形腫瘍のレドックスイメージングと核医学イメージングの評価系と応用に関する実験も開始した。昨年度は可搬型ESRイメージング装置の基礎評価を中心に実施した。3CP、CTPOならびにTempolの3種類のニトロオキサイドプローブを用いて、生体関連還元性物質であるアスコルビン酸と混合した後のESRイメージングをインビトロの系で検討した。その結果はそれぞれのプローブに対する減衰速度は既報の結果とほぼ同様であった。さらに、小バイアルに封入したニトロオキサイドプローブのESRイメージングによって明瞭な3Dイメージング画像を取得することができ、来年度の実験動物への適用の可能性を明らかにした。
    Japan Society for the Promotion of Science, Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)), Hokkaido University, 20KK0250
  • Development of a method of 3D oxygen and pH mapping of tumors using electron spin resonance spectroscopy
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2019 - 31 Mar. 2022
    Hirata Hiroshi
    We aimed to develop quantitative imaging techniques for the partial pressure of oxygen and extracellular pH for malignant tumors. In this study, electron spin resonance (ESR) spectroscopy was applied to the three-dimensional mapping of the partial pressure of oxygen and pH in solution samples. Using a molecular probe that can concurrently detect the partial pressure of oxygen and pH, we showed the feasibility of concurrent mapping the partial pressure of oxygen and pH in solution samples.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 19H02146
  • Development of a novel radiotherapy targeting iron-dependent cell death ferroptosis
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2019 - 31 Mar. 2022
    YASUI HIRONOBU
    In this study, (1) we searched for a point of action that can effectively induce ferrotosis with various candidate drugs, (2) we show evidence of the obtained mechanism of radiosensitizing action, and (3) therapeutic effect at the biological level. The ultimate goal was to develop an imaging method that could support this. Toward this goal, during this study, ferroptosis inducers were shown to increase radiosensitivity by reducing antioxidants in cancer cells, and intracellular iron metabolism in cancer cells by transferrin probes. Focusing on the mechanism, we succeeded in developing a method that makes it possible to predict the therapeutic effect of ferrotosis-induced cancer in advance.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 19H04264
  • Development of a MS imaging-based diagnosis for novel cancer senotherapy
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)
    28 Jun. 2019 - 31 Mar. 2021
    Yasui Hironobu
    Permanently stopping the cell cycle, that is, senescence, is considered to be an effective therapeutic strategy for cancer cells having infinite proliferation ability. The purpose of this study was to develop a new therapeutic method targeting cellular senescence and to establish a method that can diagnose it. First, it was clarified that senescence can be efficiently induced by the combination with radiation and Id-1 inhibition, which is known as a senescence-inducing factor in human-derived cancer cells and mouse-derived cancer cells both in vitro and in vivo. Although mass spectrometry could not determine the degree of senescence induction in this model, it revealed that 18F-FLT PET imaging may be effective as a method for detecting senescence.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Hokkaido University, 19K22586
  • Development of new therapeutic strategies for hypoxic tumors
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2018 - 31 Mar. 2021
    Shiga Tohru
    "Does eribulin improve tumor hypoxia? "To what extent does it improve the efficacy of chemotherapy and radiotherapy? "To what extent does it improve the efficacy of chemotherapy and radiotherapy?" and "Does it improve the prognosis as a result? We planned to conduct animal experiments and clinical trials to answer these three questions.
    In animal experiments using transplanted human breast cancer cells, we were able to show that 1) eribulin improves tumor hypoxia, 2) significantly slows tumor growth after radiotherapy, and 3) significantly improves survival. We also found that eribulin improved tumor oxygenation in a dose-dependent manner, with maximum oxygenation occurring 7 days after administration.
    The human study was planned as a specific clinical trial, but POC was not obtained.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), 18H02757
  • Development of a therapeutic effect evaluation system that simultaneously considers the dose rate of proton beam irradiation and LET fluctuations
    Grants-in-Aid for Scientific Research
    01 Apr. 2018 - 31 Mar. 2021
    Matsuura Taeko
    In the scanning beam delivery of protons, different portions of the target are irradiated with different linear energy transfer protons with various time intervals and irradiation times. To evaluate the sublethal damage (SLD) repair effect in prolonged scanning proton irradiation using the biophysical model, we extended the dose protraction factor in the LQ model for the arbitrary number of different LET proton irradiations delivered sequentially with arbitrary time lags, referring to the theory of dual radiation action (TDRA). The model enables us to evaluate the biological effectiveness in clinical settings within a reasonable calculation time. In addition, we have performed the cell experiment using proton beam to investigate the LET dependence of the SLD repair time.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 18K07621
  • Development of a novel therapy by targeting for cancer specific glutamine and acetate metabolism
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2017 - 31 Mar. 2020
    Inanami Osamu
    In this study, in order to clarify a novel metabolic target of radiotherapy for cancer, we established a mitochondrial-dependent metabolic assay for cancer metabolism using electron spin resonance (ESR) with a new oxygen probe. Using this method, it was clarified that ATP production by not only glucose metabolism but also electron transport system (ETC) was increased by irradiation as a survival strategy of solid tumors. Furthermore, we have found that this radiation-induced energy response can induce strong radiosensitization by glutaminolysis involved in the TCA cycle and mitochondrial inhibitory drugs. In particular, it was demonstrated that glutamine synthase inhibitors and ETC inhibitors can cause a strong radiosensitizing effect.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 17H03920
  • Establishment of a new evaluation of tumor hypoxia using FDiFA-PET
    Grants-in-Aid for Scientific Research
    01 Apr. 2017 - 31 Mar. 2020
    Okamoto Shozo
    We performed FDiFA-PET on eight healthy subjects and confirmed the safety and comparable image quality for hypoxic evaluation in less time than a conventional FMISO-PET. This result suggests a reduced patient load and inconvenience in pre-treatment hypoxic evaluation.
    On the other hand, FMISO-PET confirmed that the prognosis of patients with accumulation in lesions was worse than that of patients with accumulation on FDG-PET alone. That result indicates the hypoxic PET is useful for predicting prognosis and necessitated new treatment strategies for these patients.
    Regarding pre-clinical study, animal stdies were also performed. It was suggested that high contrast images were obtained with FDiFA-PET in tumor-muscle ratio than FMISO-PET for several malignant tumors. That suggests FDiFA-PET can detect gypoxic area earlier than conventional FMISO-PET.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 17K10428
  • Role of Id protein in radioresponse of solid tumor
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2015 - 31 Mar. 2018
    Yasui Hironobu
    Recently, inhibitor of differentiation/DNA binding 1 (Id1) has been reported to play an important role in cellular processes such as proliferation and metastasis in cancer cells. However, the role of Id1 in the radioresistance of cancer cells remains unclear. In this study, knockdown of Id1 by its specific siRNA enhanced radiosensitivity of A549 cells expressing wild-type p53, but had little effect on HeLa or HT29 cells with aberrant p53 status. The population of senescent cells remarkably increased after X-irradiation in A549 cells, and this increase was enhanced by knockdown of Id1. X-ray-induced expression of p21, a key regulator for cellular senescence, was significantly higher in Id1-knockdowned cells compared with control cells. These results indicate that Id1 contributes to the radioresistance of cancer cells via downregulation of radiation-induced senescence, suggesting that Id1 is a potent target to increase the effectiveness of cancer radiotherapy in some types of cancer.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 15K09983
  • Multiple functional electron paramagnetic resonance imaging for quantitative cancer studies
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    01 Apr. 2014 - 31 Mar. 2018
    Hirata Hiroshi
    We developed the methods of continues-wave electron spin resonance (ESR) imaging for the visualization of oxygen partial pressure and pH of tumor tissues. Using accelerated four-dimensional spectral-spatial imaging, mapping of oxygen partial pressure and pH performed. ESR imaging recorded relaxation time T2* of oxygen-sensitive spin probes and ESR spectral lines of a pH-sensitive spin probe for oxygen mapping and pH mapping. Estimations of oxygen partial pressure and pH used those spectral parameters. Finally, we tested the developed methods with solution phantoms and tumor-bearing mice.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, Competitive research funding, 26249057
  • The effect of ionizing radiation on secretory phenotype of cancer-associated fibroblasts and its impact on cancer pathophysiology
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2014 - 31 Mar. 2017
    Yamamori Tohru
    Recent evidence suggests that cancer-associated fibroblasts (CAFs), which are the most abundant cell type in cancer stroma, and CAF-derived secretory factors play important roles in various aspects of cancer pathophysiology. This study was aimed to understand how ionizing radiation influences on CAFs and their secretory phenotype. We revealed that X-irradiation to mouse embryonic fibroblasts (MEFs) increased the number of senescent cells, which are reported to have similar characteristics to CAFs. This event was accompanied by the induction of multiple cytokines. We also found that X-irradiation enhanced cellular oxidative stress level and NADPH oxidase 4 protein (NOX4) was in part responsible for it. Furthermore, our data suggested that NOX4 was not involved in the induction of secretory factors in irradiated MEFs.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 26461875
  • The basic study for evaluation and control of the influence of intermittent hypoxia on metastatic potential of tumor cells
    Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    01 Apr. 2013 - 31 Mar. 2015
    YASUI Hironobu
    In this study, I revealed the biological effect of intermittent hypoxia on the metastatic potential in tumor cells and the influence of X-irradiation on the surrounding cells as a by-stander effect as follows;
    1.The preconditioning of tumor cells with intermittent hypoxia increased the migration and invasion potentials compared to normoxia and persistent hypoxia.
    2.The conditioned medium of irradiated cell (CM) enhanced invasive ability of cancer cells. EGF mRNA and EGF concentrations was increased in X-irradiated cells and in the CM, respectively. Combined with the result that the CM activated EGFR, it is suggested that X-irradiation induces EGF expression of tumor cells, and increased EGF concentration in the CM, resulting in higher invasive ability of the surrounding cells.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 25861045
  • Characterization of malignant glioma and development of potent treatment strategy focusing on hypoxia dynamics
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    01 Apr. 2012 - 31 Mar. 2014
    INANAMI Osamu; YAMAMORI Tohru; YASUI Hironobu
    The purpose of this study is to clarify the hypothesis that the frequency of tumor hypoxia influences the prognosis of malignant glioma rather than an amount of tumor hypoxia. The results revealed that sequential PET analysis using 18F-FMISO could not visualize the transient hypoxia in glioma, because it took the relatively long time for the radioactivity attenuation. However, this study achieved the establishment of hypoxia imaging in transplanted murine glioma by using electron spin resonance technique. Furthermore, it was revealed that doranidazole is a potent drug to improve the radiation efficiency against hypoxic glioma cells.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Coinvestigator not use grants, Competitive research funding, 24659551
  • Investigation on the molecular mechanism of increased radioresistance in cancer cells exposed to intermittent hypoxia
    Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    2011 - 2012
    YASUI Hironobu
    In this study, I revealed the molecular mechanism of intermittent hypoxia-induced rasioresistance in tumor cells as follows;
    The preconditioning of tumor cells with intermittent hypoxia increased the radioresistance compared to normoxia and persistent hypoxia.
    The treatment of intermittent hypoxia induced the production of reactive oxygen species and the over-expression of the hypoxia inducible factor-1α, suggesting the involvement of cellular redox status and hypoxia-response signal pathway in the biological effect of intermittent hypoxia.
    The treatment of intermittent hypoxia decreased the fraction of the relative radiosensitive early S phase and increased that of the radioresistant G2 phase.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 23791375
  • BOLD-fMRI法による固形腫瘍低酸素領域に対する新規抗癌剤の非侵襲的薬効評価
    科学研究費助成事業 特別研究員奨励費
    2008 - 2009
    安井 博宣
    固形腫瘍内には酸素濃度の低い低酸素細胞が存在し、医療のみならず獣医療において放射線治療後のがんの再発の原因となっている。本研究では制がん剤エチニルシチジン(ECyd)が、この低酸素細胞に抗腫瘍作用を示すか否かを検討した。まず、大気条件下および低酸素条件下で培養された腫瘍細胞に対して、ECydがX線による細胞死を増強するかを検討したところ、酸素濃度に依存せずアポトーシスおよび増殖死を増強することを明らかにした。次に低酸素細胞の放射線抵抗性の原因となっているとされるsurvivin、c-IAP2,HIF-1・に対するECydの効果を検討したところ、分子生物学的手法によりこれらの蛋白質は転写調節を受け発現が抑制されていた。以上の結果に加え、マウスに移植した固形腫瘍を用いてECydの放射線増感作用を検討したところ、細胞培養系と同様にECydによるHIF-1・発現の抑制と低酸素細胞に対するアポトーシス誘導が観察された。加えて、低酸素マーカーpimonidazoleを用いた免疫染色を行ったところ、X線照射とECyd投与の併用により低酸素領域の有意な縮小が起こることを示した。以上の結果は、ECydが低酸素細胞に対しても細胞死を誘導できる点で有望な放射線増感剤となりうる可能性を示したものであり、その成果は国際誌British Journal of Cancer誌に掲載受理された。またマウスに移植した固形腫瘍内の酸素濃度pO2を経時的かつ非侵襲的に計測する手法として、ESRオキシメトリー法を確立した。具体的には、L-band ESR装置にサーフェスコイル型共振器を取り付けることで動物の皮膚表面に移植した腫瘍の酸素濃度を測定できるようにした。また酸素感受性プローブとして、生体内で安定かつESRスペクトル線幅の狭いlithium octa-n-butoxy-2,3-naphthalo-cyanine(LiNc-BuO)を用いた。移植固形腫瘍にLiNc-BuO懸濁液を埋め込み、pO2を計測したところ腫瘍成長に伴って低酸素化が進んでいることが明らかとなった。この実験系が確立したことで、今後、薬剤や放射線による腫瘍内酸素濃度の変動を同一個体で評価することが可能となり、その意義は大きいと考えられる。
    日本学術振興会, 特別研究員奨励費, 北海道大学, 07J05083
■ Industrial Property Rights
  • 放射線増感剤
    Patent right, 山本拓矢; 王钰博; 稲波 修; 安井博宣; 臼田史仁
    特願2023-182412, 24 Oct. 2023
  • ジクロロ酢酸を側鎖に担持する親水-疎水性共重合体及びそれらの医療用途
    Patent right, 長崎幸夫; 安井博宣; 山田さと; 稲波修, 筑波大学, 北海道大学
    特願2023-168768, 28 Sep. 2023
  • 陽子線治療用増感剤および陽子線治療方法
    Patent right, 稲波修; 白土博樹; 松田彰; 山盛徹; 安井博宣; 前田憲一郎
    特願2015-104243, 22 May 2015
    特開2016- 216404, 22 Dec. 2016
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Industrial Property Rights
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