Faculty of Science and Engineering, Graduate School of Information, Production, and Systems

Job title


Degree 【 display / non-display

  • 東北大学   博士(工学)

Research Experience 【 display / non-display

  • 2021.04

    Waseda University   Graduate School of Information Production and Systems   Professor

  • 2003.04

    National Institute of Advanced Industrial Science & Technology (AIST)   Biomedical Research Institute   Senior Research Scientist


Research Areas 【 display / non-display

  • Biomedical engineering

Research Interests 【 display / non-display

  • 5-aminolevulinic acid

  • radiotherapy

  • radiosensitizer

  • gene expression analysis

  • radiodynamic therapy

Papers 【 display / non-display

  • DNA Strand Break Properties of Protoporphyrin IX by X-Ray Irradiation against Melanoma.

    Takema Hasegawa, Junko Takahashi, Shinsuke Nagasawa, Motomichi Doi, Akihiro Moriyama, Hitoshi Iwahashi

    International journal of molecular sciences   21 ( 7 )  2020.03  [Refereed]  [International journal]

     View Summary

    Recent reports have suggested that 5-aminolevulinic acid (5-ALA), which is a precursor to protoporphyrin IX (PpIX), leads to selective accumulation of PpIX in tumor cells and acts as a radiation sensitizer in vitro and in vivo in mouse models of melanoma, glioma, and colon cancer. In this study, we investigated the effect of PpIX under X-ray irradiation through ROS generation and DNA damage. ROS generation by the interaction between PpIX and X-ray was evaluated by two kinds of probes, 3'-(p-aminophenyl) fluorescein (APF) for hydroxyl radical (•OH) detection and dihydroethidium (DHE) for superoxide (O2•-). •OH showed an increase, regardless of the dissolved oxygen. Meanwhile, the increase in O2•- was proportional to the dissolved oxygen. Strand breaks (SBs) of DNA molecule were evaluated by gel electrophoresis, and the enhancement of SBs was observed by PpIX treatment. We also studied the effect of PpIX for DNA damage in cells by X-ray irradiation using a B16 melanoma culture. X-ray irradiation induced γH2AX, DNA double-strand breaks (DSBs) in the context of chromatin, and affected cell survival. Since PpIX can enhance ROS generation even in a hypoxic state and induce DNA damage, combined radiotherapy treatment with 5-ALA is expected to improve therapeutic efficacy for radioresistant tumors.

    DOI PubMed

  • Screening of X-ray responsive substances for the next generation of radiosensitizers.

    Akihiro Moriyama, Takema Hasegawa, Lei Jiang, Hitoshi Iwahashi, Takashi Mori, Junko Takahashi

    Scientific reports   9 ( 1 ) 18163 - 18163  2019.12  [Refereed]  [International journal]

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    X-ray responsivity resulting in the generation of reactive oxygen species (ROS) was investigated in 9600 organic compounds that were selected by considering their structural diversity. We focused on superoxides that were primarily detected using dihydroethidium (DHE) and hydroxyl radicals, that were identified fluorometrically using 3'-(p-aminophenyl) Fluorescein (APF). Many organic compounds were discovered that responded to the DHE and/or APF assay using X-ray irradiation. These results suggest that some of these organic compounds emit either superoxides or hydroxyl radicals whereas others emit both under the influence of X-ray irradiation. The response of the derivatives of a hit compound with a partial change in the structure was also investigated. The products produced from DHE by X-ray irradiation were identified by HPLC to confirm the integrity of the process. Although, the reactions were suppressed by the superoxide dismutase (SOD), not only 2-hydroxyethidium (2-OH-E+), but also ethidium (E+) were detected. The results suggest that apart from a direct reaction, an indirect reaction may occur between DHE and the superoxides. Although X-ray responsiveness could not be inferred due to the molecular complexity of the investigated compounds, delineation of these reactions will facilitate the development of the next generation of radiosensitizers.

    DOI PubMed

  • Verification of 5-Aminolevurinic Radiodynamic Therapy Using a Murine Melanoma Brain Metastasis Model.

    Junko Takahashi, Shinsuke Nagasawa, Mitsushi J Ikemoto, Chikara Sato, Mari Sato, Hitoshi Iwahashi

    International journal of molecular sciences   20 ( 20 )  2019.10  [Refereed]  [International journal]

     View Summary

    Melanoma is a highly aggressive cancer with a propensity for brain metastases. These can be treated by radiotherapy, but the radiation-resistant nature of melanoma makes the prognosis for melanoma patients with brain metastases poor. Previously, we demonstrated that treatment of mice with subcutaneous melanoma with 5-aminolevurinic acid (5-ALA) and X-rays in combination, ("radiodynamic therapy (RDT)"), instead of with 5-ALA and laser beams ("photodynamic therapy"), improved tumor suppression in vivo. Here, using the B16-Luc melanoma brain metastasis model, we demonstrate that 5-ALA RDT effectively treats brain metastasis. We also studied how 5-ALA RDT damages cells in vitro using a B16 melanoma culture. Cell culture preincubated with 5-ALA alone increased intracellular photosensitizer protoporphyrin IX. On X-ray irradiation, the cells enhanced their ∙OH radical generation, which subsequently induced γH2AX, a marker of DNA double-strand breaks in their nuclei, but decreased mitochondrial membrane potential. After two days, the cell cycle was arrested. When 5-ALA RDT was applied to the brain melanoma metastasis model in vivo, suppression of tumor growth was indicated. Therapeutic efficacy in melanoma treatment has recently been improved by molecular targeted drugs and immune checkpoint inhibitors. Treatment with these drugs is now expected to be combined with 5-ALA RDT to further improve therapeutic efficacy.

    DOI PubMed

  • Assessment of harmfulness and biological effect of carbon fiber dust generated during new carbon fiber recycling method.

    Akihiro Moriyama, Takema Hasegawa, Chisato Nagaya, Kazuhiro Hamada, Takehiro Himaki, Mami Murakami, Masanori Horie, Junko Takahashi, Hitoshi Iwahashi, Hiroshi Moritomi

    Journal of hazardous materials   378   120777 - 120777  2019.10  [Refereed]  [International journal]

     View Summary

    Concern over the effects of nanomaterials on human health has risen due to the dramatic advances in the development of various technologies based on nanomaterials. Gifu Prefecture and Gifu University are developing technologies for recycling used carbon fiber because the waste disposal process is highly cost and energy intensive. However, generation of carbon fiber dust during the recycling process is a serious issue, especially in the occupational environment. Recycling requires carbonization by partial firing treatment at 500℃ followed by firing treatment at 440℃: these processes produce dust as a by-product. It is important to study the influence of carbon fibers on human health at a molecular level. In this study, three types of carbon fibers - before recycling, after carbonization, and after firing were evaluated for their toxic effects on mice. During the breeding period, no loss in body weight was confirmed. Further, by staining the lung tissue sections, it was found that pulmonary fibrosis did not occur. We found that these carbon fibers might not possess severe toxicity. However, we also found that the toxicity varies according to firing treatment. Furthermore, we found that firing treatment reduces the potential hazard to human health.

    DOI PubMed

  • The Truth of Toxicity Caused by Yttrium Oxide Nanoparticles to Yeast Cells.

    Akihiro Moriyama, Ukyo Takahashi, Youta Mizuno, Junko Takahashi, Masanori Horie, Hitoshi Iwahashi

    Journal of nanoscience and nanotechnology   19 ( 9 ) 5418 - 5425  2019.09  [Refereed]  [International journal]

     View Summary

    Yttrium oxide (Y₂O₃) nanoparticles have widespread applications; however, toxicity due to these nanoparticles has also been reported. In this study, we evaluated the in vitro toxicity of Y₂O₃ nanoparticles according to the technical specifications published by the International Standard Organization (ISO/TS 19337:2016). We used Saccharomyces cerevisiae as a model microorganism represented the environment. We carried out catch ball analysis of yttrium oxide and yttrium ion toxicities. The result showed that Y₂O₃ nanoparticles (20 mg/5 ml) and YCl₃ (5 mg/5 ml) treatment caused oxidative stress in yeast cells. Based on transcriptome analysis, fluorescent spectroscopy, and solubility analysis of Y₂O₃ nanoparticles, we conclude that the toxicity is due to yttrium ions derived from the nanoparticles. The ions induce oxidative stress and cause protein denaturation, which in turn induces proteasome formation to eliminate denatured proteins. Yttrium nanoparticles induce oxidative stress, which has associated with heavy metal ions. Thus, the use of yttrium nanoparticles or yttrium ions must be controlled like heavy metals.

    DOI PubMed

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Misc 【 display / non-display

  • 抗体リポソームによる金ナノ粒子放射線増感剤の細胞取込み

    三澤 雅樹, 大森 拓也, 清水 森人, 佐藤 昌憲, 松本 孔貴, 高橋 淳子

    日本DDS学会学術集会プログラム予稿集   33回   181 - 181  2017.06

  • X線照射による金ナノ粒子の増感作用と細胞ストレス応答

    三澤 雅樹, 早野 将史, 清水 森人, 佐藤 昌憲, 松本 孔貴, 高橋 淳子

    日本DDS学会学術集会プログラム予稿集   32回   178 - 178  2016.06

  • 職歴を振り返って(女性研究者のキャリアを考える)

    高橋 淳子

    生物工学会誌 : seibutsu-kogaku kaishi   89 ( 10 ) 621 - 622  2011


  • 1104 Structural Evaluation of Regenerated Bone and Cartilage by a Micro-focus X-ray CT

    MISAWA Masaki, HAYASHI Kazuhiko, SHIRASAKI Yoshio, TAKAHASHI Junko

    The Proceedings of Ibaraki District Conference   2010 ( 0 ) 307 - 308  2010

     View Summary

    Bone-cartilage bi-phase element was constructed of native chondrocyte of beagle and P-TCP scaffold block. Assembling such a regenerative element enables to form arbitral configuration which fits the shape of large defect on joints without sacrificing other part of the body. The bone-cartilage bi-phase element was grafted in a distal femur condyle of a beagle for 2 month. The extracted femur sample including the bi-phase element was scanned by a high-resolution, micro-focus X-ray tomography to investigate the fusion process in vivo. The 3D tomography measurement showed that the hosting cancellous bone intruded into the scaffold and a part of the scaffold was replaced with the cancellous bone. Mechanical properties of grafted element was evaluated by a push-out test, indicating that scaffold was firmly fused with the cancellous bone of the host. Also, a preliminary microarray gene expression analysis was conducted to investigate the effect of X-ray radiation on the regenerative devices.


Industrial Property Rights 【 display / non-display

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Syllabus 【 display / non-display

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