Updated on 2024/12/08

写真a

 
TAKAHASHI, Junko
 
Affiliation
Faculty of Science and Engineering, Graduate School of Information, Production, and Systems
Job title
Professor(non-tenure-track)
Degree
博士(工学) ( 東北大学 )

Research Experience

  • 2021.04
    -
    Now

    Waseda University   Graduate School of Information Production and Systems   Professor

  • 2003.04
    -
    2021.03

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

Research Areas

  • Biomedical engineering

Research Interests

  • radiodynamic therapy

  • 5-aminolevulinic acid

  • radiotherapy

  • radiosensitizer

  • gene expression analysis

  • bioinfomatics

▼display all

 

Papers

  • Reliability evaluation of thick Ag wire bonding on Ni pad for power devices

    Xing Wei, Di Xin, Isamu Morisako, Junko Takahashi, Kohei Tatsumi

    Microelectronics Reliability   152   115304 - 115304  2024.01  [Refereed]

    DOI

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    1
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  • A systematic review on the development of radiosensitizers, with cancer selectivity, for radiotherapy using ionizing radiation

    Hengmao Zhang, Haobo Zhao, Ming Chi, Kaizhen Yang, Yukang Chen, Jiahui Mao, Peilin Li, Zukang Wang, Faqiao Song, Wenxuan Guo, Miyu Sakai, Junko Takahashi

    AIMS Bioengineering   10 ( 2 ) 89 - 110  2023  [Refereed]

    Authorship:Corresponding author

     View Summary

    <p lang="fr">&lt;abstract&gt;&lt;sec&gt;&lt;title&gt;Background&lt;/title&gt;&lt;p&gt;At present, radiotherapy (RT) is widely used in cancer treatment, but traditional RT methods using ionizing radiation cannot avoid damage to normal tissues. Therefore, the development of a more precise RT is an important research direction for relevant researchers. Concurrently, research on radiosensitizers (RSs) using nanotechnology is developing rapidly, and RSs that are selective for cancerous tissues or cancer cells may become an important part of future precision RT.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;Methods&lt;/title&gt;&lt;p&gt;Using RSs and RT as keywords, the relevant papers in the PubMed database from 2013 to 2022 were summarized. Articles on RS with selectivity to cancer tissue were collected. Among the selected articles, RSs were classified into “active selectivity”, “passive selectivity” and “others” according to the different selectivity principles of RSs.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;Results&lt;/title&gt;&lt;p&gt;A total of 771 articles were retrieved from PubMed. After screening, the research content of the remaining 79 articles was found to be related to the selectivity of RSs to cancer tissues. Among them, 28 articles were classified as “active selectivity”, and most of the sensitizers in this category could target specific targets in cancer tissues. There were 30 papers classified as “passive selectivity” and the selectivity principles were mainly the enhanced permeability and retention (EPR) effect, aggregation caused by pH sensitivity, and aggregation in anoxic environments. There were 21 papers classified as “others”. The sensitizers in these studies showed selectivity for cancer tissue, but the mechanism was not clear. This review attempts to summarize studies on RSs that are selective for cancer tissues.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;Conclusions&lt;/title&gt;&lt;p&gt;We reviewed nearly ten years of literature on selective RSs and classified the selectivity of different RSs into active and passive selectivities.&lt;/p&gt;&lt;/sec&gt;&lt;/abstract&gt;</p>

    DOI

  • In Vivo Study of the Efficacy and Safety of 5-Aminolevulinic Radiodynamic Therapy for Glioblastoma Fractionated Radiotherapy.

    Junko Takahashi, Shinsuke Nagasawa, Motomichi Doi, Masamichi Takahashi, Yoshitaka Narita, Junkoh Yamamoto, Mitsushi J Ikemoto, Hitoshi Iwahashi

    International journal of molecular sciences   22 ( 18 )  2021.09  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    To treat malignant glioma, standard fractionated radiotherapy (RT; 60 Gy/30 fractions over 6 weeks) was performed post-surgery in combination with temozolomide to improve overall survival. Malignant glioblastoma recurrence rate is extremely high, and most recurrent tumors originate from the excision cavity in the high-dose irradiation region. In our previous study, protoporphyrin IX physicochemically enhanced reactive oxygen species generation by ionizing radiation and combined treatment with 5-aminolevulinic acid (5-ALA) and ionizing radiation, while radiodynamic therapy (RDT) improved tumor growth suppression in vivo in a melanoma mouse model. We examined the effect of 5-ALA RDT on the standard fractionated RT protocol using U251MG- or U87MG-bearing mice. 5-ALA was orally administered at 60 or 120 mg/kg, 4 h prior to irradiation. In both models, combined treatment with 5-ALA slowed tumor progression and promoted regression compared to treatment with ionizing radiation alone. The standard fractionated RT protocol of 60 Gy in 30 fractions with oral administration of 120 and 240 mg/kg 5-ALA, the human equivalent dose of photodynamic diagnosis, revealed no significant increase in toxicity to normal skin or brain tissue compared to ionizing radiation alone. Thus, RDT is expected to enhance RT treatment of glioblastoma without severe toxicity under clinically feasible conditions.

    DOI PubMed

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    8
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  • Detection and monitoring of insect traces in bioaerosols

    Panyapon Pumkaeo, Junko Takahashi, Hitoshi Iwahashi

    PeerJ   9  2021.02  [Refereed]

     View Summary

    Studies on bioaerosols have primarily focused on their chemical and biological compositions and their impact on public health and the ecosystem. However, most bioaerosol studies have only focused on viruses, bacteria, fungi, and pollen. To assess the diversity and composition of airborne insect material in particulate matter (PM) for the first time, we attempted to detect DNA traces of insect origin in dust samples collected over a two-year period. These samples were systematically collected at one-month intervals and categorized into two groups, PM2.5 and PM10, based on the aerodynamic diameter of the aerosol particles. Cytochrome-c oxidase I (COI) was the barcoding region used to identify the origins of the extracted DNA. The airborne insect community in these samples was analyzed using the Illumina MiSeq platform. The most abundant insect sequences belonged to the order Hemiptera (true bugs), whereas order Diptera were also detected in both PM2.5 and PM10 samples. Additionally, we inferred the presence of particulates of insect origin, such as brochosomes and integument particles, using scanning electron microscopy (SEM). This provided additional confirmation of the molecular results. In this study, we demonstrated the benefits of detection and monitoring of insect information in bioaerosols for understanding the source and composition. Our results suggest that the PM2.5 and PM10 groups are rich in insect diversity. Lastly, the development of databases can improve the identification accuracy of the analytical results.

    DOI

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    15
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    (Scopus)
  • BIOLOGICAL TRACE INFORMATION EXTRACTED FROM BIOAEROSOLS USING NGS ANALYSIS

    Panyapon Pumkaeo, Wenhao Lu, Youki Endou, Tomofumi Mizuno, Junko Takahashi, Hitoshi Iwahashi

    Bioscience Journal   37  2021.01  [Refereed]

     View Summary

    Bioaerosols are atmospheric particles with a biological trace, such as viruses, bacteria, fungi, and plant material such as pollen and plant debris. In this study, we analyzed the biological information in bioaerosols using next generation sequencing of the trace DNA. The samples were collected using an Andersen air sampler and separated into two groups according to particulate matter (PM) size: small (PM2.5) and large (PM10). Amplification and sequencing of the bacterial 16S rDNA gene, prokaryotic internal transcribed spacer 1 (ITS1) region and DNA sequence of a plant chloroplast gene (rbcL) were carried out using several sets of specific primers targeting animal and plant sequences. Lots of bacterial information was detected from the bioaerosols. The most abundant bacteria in several samples were of the Actinobacteria (class), Alphaproteobacteria, Bacilli, and Clostridia. For the animal detection using internal transcribed spacer 1, only uncultured fungi were detected in more than half of the hits, with a high number of Cladosporium sp. in the samples. For the plant identification, the ITS1 information only matched fungal species. However, targeting of the rbcL region revealed diverse plant information, such as Medicago papillosa. In conclusion, traces of bacteria, fungi, and plants could be detected in the bioaerosols, but not of animals using our primers.

    DOI

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  • Detection and monitoring of insect traces in bioaerosols.

    Panyapon Pumkaeo, Junko Takahashi, Hitoshi Iwahashi

    PeerJ   9   e10862  2021  [International journal]

     View Summary

    Studies on bioaerosols have primarily focused on their chemical and biological compositions and their impact on public health and the ecosystem. However, most bioaerosol studies have only focused on viruses, bacteria, fungi, and pollen. To assess the diversity and composition of airborne insect material in particulate matter (PM) for the first time, we attempted to detect DNA traces of insect origin in dust samples collected over a two-year period. These samples were systematically collected at one-month intervals and categorized into two groups, PM2.5 and PM10, based on the aerodynamic diameter of the aerosol particles. Cytochrome-c oxidase I (COI) was the barcoding region used to identify the origins of the extracted DNA. The airborne insect community in these samples was analyzed using the Illumina MiSeq platform. The most abundant insect sequences belonged to the order Hemiptera (true bugs), whereas order Diptera were also detected in both PM2.5 and PM10 samples. Additionally, we inferred the presence of particulates of insect origin, such as brochosomes and integument particles, using scanning electron microscopy (SEM). This provided additional confirmation of the molecular results. In this study, we demonstrated the benefits of detection and monitoring of insect information in bioaerosols for understanding the source and composition. Our results suggest that the PM2.5 and PM10 groups are rich in insect diversity. Lastly, the development of databases can improve the identification accuracy of the analytical results.

    DOI PubMed

    Scopus

    15
    Citation
    (Scopus)
  • Immunostimulatory Effects of Radiotherapy for Local and Systemic Control of Melanoma: A Review.

    Junko Takahashi, Shinsuke Nagasawa

    International journal of molecular sciences   21 ( 23 )  2020.12  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Recently, modern therapies involving immune checkpoint inhibitors, cytokines, and oncolytic virus have been developed. Because of the limited treatment effect of modern therapy alone, the immunostimulatory effect of radiotherapy attracted increasing attention. The combined use of radiotherapy and modern therapy has been examined clinically and non-clinically, and its effectiveness has been confirmed recently. Because melanomas have high immunogenicity, better therapeutic outcomes are desired when using immunotherapy. However, sufficient therapeutic effects have not yet been achieved. Thus far, radiotherapy has been used only for local control of tumors. Although extremely rare, radiotherapy has also been reported for systemic control, i.e., abscopal effect. This is thought to be due to an antitumor immune response. Therefore, we herein summarize past information on not only the mechanism of immune effects on radiotherapy but also biomarkers reported in case reports on abscopal effects. We also reviewed the animal model suitable for evaluating abscopal effects. These results pave the way for further basic research or clinical studies on new treatment methods for melanoma. Currently, palliative radiation is administered to patients with metastatic melanoma for local control. If it is feasible to provide both systemic and local control, the treatment benefit for the patients is very large.

    DOI PubMed

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    22
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  • 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]

    Authorship:Corresponding author

     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

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    15
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  • 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]

    Authorship:Corresponding author

     View Summary

    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

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    5
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  • 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]

    Authorship:Lead author, Corresponding author

     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

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    13
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  • 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

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    22
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  • 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

  • Relationship between Flavonoid Structure and Reactive Oxygen Species Generation upon Ultraviolet and X-ray Irradiation

    Jiang, L, Yanase, E, Mori, T, Kurata, K, Toyama, T, Tsuchiya, A, Yamauchi, K, Mitsunaga, T, Iwahashi, H, Takahashi, J

    Journal of Photochemistry & Photobiology A: Chemistry   384   112044  2019  [Refereed]

     View Summary

    In this research, we aimed to reveal structures related to reactive oxygen species (ROS) generation of flavonoids upon ultraviolet (UV) or X-ray irradiation. ROS production of selected flavonoids was studied by using ROS fluorescence probes. We discuss the relationship between the structures of the flavonoids and the generation of three ROSs, superoxide anion radical (O-2(center dot-)), hydroxyl radical ((OH)-O-center dot), and singlet oxygen (O-1(2)). Results showed that 2,3-double bond was an key structure for natural flavonoids to generate O-2(center dot-). We also discuss the effects of the ROS scavenging capacities on ROS generation through oxygen radical absorbance capacity (ORAC) tests. Derivatives of quercetin could produce (OH)-O-center dot due to differences of ROS scavenging ability. Our results indicated that flavonoids and their derivatives, which were used as antioxidant reagents, can serve as ROS generators upon ultraviolet (UV) or X-ray irradiation.

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

    Moriyama, A, Takahashi, U, Mizuno,Y, Takahashi, J, Horie, M, Iwahashi, H

    Journal of Nanoscience and Nanotechnology   294   144 - 150  2019  [Refereed]

  • Evaluation of the effect of high pressure carbon dioxide-pasteurized food on animal health.

    Hibi A, Ohno, T, Moriyama, A, Himaki, T, Takahashi, J, Iwahashi, H

    High Pressure Research   39 ( 2 ) 357 - 366  2019  [Refereed]

  • Oxidative stress caused by TiO2 nanoparticles under UV irradiation is due to UV irradiation not through nanoparticles.

    Akihiro Moriyama, Ikuho Yamada, Junko Takahashi, Hitoshi Iwahashi

    Chemico-biological interactions   294   144 - 150  2018.10  [Refereed]  [International journal]

     View Summary

    Currently, nanoparticles are used in various commercial products. One of the most common nanoparticles is titanium dioxide (TiO2). It has a catalytic activity and UV absorption, and generates reactive oxygen species (ROS). This catalytic activity of TiO2 nanoparticles was believed to be capable of killing a wide range of microorganisms. In the environment, the unique properties of TiO2 nanoparticles can be maintained; therefore, the increasing use of TiO2 nanoparticles is raising concerns about their environmental risks. Thus, assessment of the biological and ecological effects of TiO2-NOAAs is necessary. In this study, we assessed the effect of TiO2-NOAAs for S. cerevisiae using DNA microarray. To compare yeast cells under various conditions, six treatment conditions were prepared (1. adsorbed fraction to TiO2-NOAA under UV; 2. non-adsorbed fraction to TiO2-NOAA under UV; 3. adsorbed fraction to TiO2-NOAA without UV; 4. non-adsorbed fraction to TiO2-NOAA without UV; 5. under UV; and 6. untreated control). The result of the DNA microarray analysis, suggested that yeast cells that are adsorbed by TiO2-NOAA under UV irradiation suffer oxidative stress and this stress response was similar to that by only UV irradiation. We concluded that the effect of TiO2-NOAAs on yeast cells under UV irradiation is not caused by TiO2-NOAA but UV irradiation.

    DOI PubMed

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    15
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  • Self-assembled nanodiamond supraparticles for anticancer chemotherapy

    Yue Yu, Masahiro Nishikawa, Ming Liu, Takahiro Tei, Sunil C. Kaul, Renu Wadhawa, Minfang Zhang, Junko Takahashi, Eijiro Miyako

    Nanoscale   10 ( 19 ) 8969 - 8978  2018.05  [Refereed]

     View Summary

    A nanodiamond (ND) is a promising material for drug delivery applications owing to its relatively low cost, amenability to large-scale synthesis, unique structure, and low toxicity. However, synthesizing drug-loaded ND conjugates with uniform and tunable sizes, high loading capacity, efficacy in drug delivery, and versatility in terms of surface functionalization has been challenging. Here, we show that perfluorooctanoic acid-functionalized NDs spontaneously transform into well-dispersed and biocompatible supraparticle (SP) nanoclusters. We demonstrate that the synthesized ND-based SPs (ND-SPs) exhibit high penetration through the cell membrane and are therefore superior as drug carriers for conventional nanomedicines such as polyethylene glycol and phospholipid-based nanocapsules and simple drug-loaded ND conjugates. We confirm the efficacy of ND-SPs in the eradication of cancer cells in vitro and in vivo. Our results demonstrate that the synthesized ND-SPs are useful for targeted drug delivery in a variety of biological applications.

    DOI PubMed

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    25
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  • Luteolin as reactive oxygen generator by X-ray and UV irradiation

    Michiru Toyama, Takashi Mori, Junko Takahashi, Hitoshi Iwahashi

    RADIATION PHYSICS AND CHEMISTRY   146   11 - 18  2018.05

     View Summary

    Non-toxic X-ray-responsive substances can be used in the radiosensitization of cancer, like porphyrin mediated radiotherapy. However, most X-ray-responsive substances are toxic. To find novel non-toxic X-ray-responsive substances, we studied the X-ray and UV reactivity of 40 non-toxic compounds extracted from plants. Dihydroethidium was used as an indicator to detect reactive oxygen species (ROS) generated by the compounds under X-ray or UV irradiation. We found that 13 of the investigated compounds generated ROS under X-ray irradiation and 17 generated ROS under UV irradiation. Only 4 substances generated ROS under both X-ray and UV. In particular, luteolin exhibited the highest activity among the investigated compounds; therefore, the ROS generated by luteolin were thoroughly characterized. To identify the ROS, we employed a combination of ROS detection reagents and their quenchers. O-2 generation by luteolin was monitored using dihydroethidium and superoxide dismutase (as an O-2(-) quencher). OH and O-1(2) generation was determined using aminophenyl fluorescein with ethanol (OH quencher) and Singlet Oxygen Sensor Green with NaN3 (O-1(2) quencher), respectively. Generation of O-2(-) under X-ray and UV irradiation was observed; however, no OH or O-1(2) was detected. The production of ROS from luteolin is surprising, because luteolin is a well-known antioxidant.

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    9
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  • Verification of radiodynamic therapy by medical linear accelerator using a mouse melanoma tumor model.

    Junko Takahashi, Mami Murakami, Takashi Mori, Hitoshi Iwahashi

    Scientific reports   8 ( 1 ) 2728 - 2728  2018.02  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Combined treatment with 5-aminolevulinic acid (5-ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from 5-ALA enhances the generation of ROS by the X-ray irradiation. In the present study, a high-energy medical linear accelerator was used instead of a non-medical low energy X-ray irradiator, which had been previously used. Tumor-bearing mice implanted with B16-BL6 melanoma cells were treated with fractionated doses of irradiation (in total, 20 or 30 Gy), using two types of X-ray irradiator after 5-ALA administration. Suppression of tumor growth was enhanced with X-ray irradiation in combination with 5-ALA treatment compared with X-ray treatment alone, using both medical and non-medical X-ray irradiators. 5-ALA has been used clinically for photodynamic therapy. Thus, "radiodynamic therapy", using radiation from medical linacs as a physical driving force, rather than the light used in photodynamic therapy, may have potential clinical applications.

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    33
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  • Oxidative stress caused by TiO2 nanoparticles under UV irradiation is due to UV irradiation not through nanoparticles.

    Moriyama, A, Yamada, I, Takahashi, J, Iwahashi H

    Chemico-Biological Interactions   19   5418 - 5425  2018  [Refereed]

  • For Novel Disease Diagnostic Markers in Blood RNA.

    Takahashi1, J, Iwahashi, H

    Journal of Medical Diagnostic   7 ( 1 ) 1000e115  2018.01  [Refereed]

    Authorship:Lead author, Corresponding author

  • RNA Quality Control Using External Standard RNA.

    Hasegawa T, Takahashi J, Iwahashi H

    Polish journal of microbiology   67 ( 3 ) 347 - 353  2018  [Refereed]

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    2
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  • Evaluation of the physiology of miniature pig fed Shochu distillery waste using mRNA expression profiling

    Shiori Miura, Junko Takahashi, Hitoshi Iwahashi

    Journal of Material Cycles and Waste Management   20 ( 1 ) 237 - 244  2018.01  [Refereed]

     View Summary

    Shochu distillery waste is the discarded material generated during Shochu production, and it has been used as feed for livestock. In this study, we evaluated the applicability of Shochu distillery waste as a livestock diet. Shochu distillery waste diet was fed to Clawn miniature pigs. At the end of the dietary period, blood samples were collected for biochemical examination and microarray analysis. No significant differences were observed between the control and Shochu distillery waste treatment groups based on physical and biochemical examination. Gene expression patterns were also similar. In addition, gene profiling of these two groups was compared with those of hyperlipidemia and toxicant model groups. Expression profiling of the two groups was different from those of the hyperlipidemia and toxicant model groups. In conclusion, the Shochu distillery waste diet did not affect pig physiology and it is a suitable substitute for standard feed. Moreover, these results promote the potential for microarray analysis use in the evaluation of food safety.

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  • The role of transcriptomics: physiological equivalence based on gene expression profiles.

    Miura, S, Himaki, T, Takahashi, J, Iwahashi, H

    Reviews in Agricultural Science   5   5:21 - 525  2017  [Refereed]

  • Introduction to 5-Aminolevulinic Acid-Protoporphyrin IX Mediated Radiodynamic Therapy (RDT)

    Takahashi, J, Iwahashi, H

    Clinics in Oncolog   2   1330  2017  [Refereed]

    Authorship:Lead author, Corresponding author

  • 2.5-aminolevulinic acid - Protoporphyrin IX mediated radiodynamic therapy (RDT)

    Takahashi, J, Iwahashi, H

    ALA porphyrin Science   5   35 - 38  2016  [Refereed]  [Invited]

    Authorship:Lead author, Corresponding author

  • Combined treatment with X-ray irradiation and 5-aminolevulinic acid elicits better transcriptomic response of cell cycle-related factors than X-ray irradiation alone

    Junko Takahashi, Masaki Misawa, Hitoshi Iwahashi

    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY   92 ( 12 ) 774 - 789  2016  [Refereed]

    Authorship:Lead author, Corresponding author

     View Summary

    Purpose: 5-Aminolevulinic acid (ALA) is a precursor of the photosensitizer protoporphyrin (PpIX) used in photodynamic therapy. In our previous work, PpIX enhanced the generation of reactive oxygen species by X-ray irradiation. In this study, we evaluated the potential of ALA as an endogenous sensitizer to X-ray irradiation.
    Methodology: Tumor-bearing C57BL/6J mice implanted with B16-BL6 melanoma cells were subsequently treated with irradiation (3Gy/day for 10 days; total, 30Gy) plus local administration of 50mg/kg ALA 24 hours prior to each irradiation (ALA-XT). Tumor-bearing mice without treatment (NT), those treated with ALA only (ALAT), and those treated with X-ray irradiation only (XT) were used as controls.
    Results: ALA potentiated tumor suppression by X-ray irradiation. In microarray analyses using tumor tissue collected after 10 sessions of fractional irradiation, functional analysis revealed that the majority of dysregulated genes in the XT and ALA-XT groups were related to cell-cycle arrest. Finally, the XT and ALA-XT groups differed in the strength of expression, but not in the pattern of expression.
    Conclusions: mRNA analysis revealed that the combined use of ALA and X-ray irradiation sensitized tumors to X-ray treatment. Furthermore, the present results were consistent with ALA's tumor suppressive effects in vivo.

    DOI

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  • Gene expression profiling can predict the fate of HeLa cells exposed to X-ray irradiation with or without protoporphyrin accumulation.

    Junko Takahashi, Masaki Misawa, Hitoshi Iwahashi

    Genomics data   5   192 - 4  2015.09  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Protoporphyrin IX (PpIX) enhances the generation of reactive oxygen species in cells following physicochemical interactions with X-rays. To evaluate the use of porphyrins as radio-sensitizers in radiotherapy, the transcriptomic effects of PpIX and/or X-ray irradiation were investigated in HeLa cells. Microarray experiments were performed using Agilent-014,850 Whole Human Genome Microarray 4x44K G4112F (GEO#: GSE61805). We selected the condition corresponding to 1 μg/mL PpIX exposure prior to 3 Gy-irradiation of cells, and collected cells 24 h post irradiation. X-ray exposure at a dose of 3 Gy did not affect cell survival 24 h post irradiation, regardless of the concentration of PpIX. Approximately 50% cells exposed to X-ray irradiation alone (XT) and 70% cells exposed to PpIX treatment for 6 h before X-ray irradiation (PpIX-XT) lost clonogenic ability. Based on p-values (p < 0.01), we selected genes for functional analysis. The majority of the regulated genes in the XT and PpIX-XT groups were related to cell cycle arrest. Furthermore, transcriptome analysis of the cells collected 24 h post irradiation revealed the fate of the cells that lost clonogenic ability due to cell cycle arrest.

    DOI PubMed

    Scopus

    1
    Citation
    (Scopus)
  • Transcriptome Analysis of Porphyrin-Accumulated and X-Ray-Irradiated Cell Cultures under Limited Proliferation and Non-Lethal Conditions.

    Takahashi J, Misawa M, Iwahashi H

    Microarrays (Basel, Switzerland)   4 ( 1 ) 25 - 40  2015.01  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    5-Aminolevulinic acid (ALA) is a precursor of the photosensitizer used in photodynamic therapy. It accumulates in tumor cells and subsequently metabolizes to protoporphyrin IX (PpIX), which generates singlet oxygen after light irradiation. PpIX enhances the generation of reactive oxygen species following physicochemical interactions with X-rays. ALA-based treatment using fractionated doses of irradiation suppressed tumor growth in a mouse melanoma model. To study the transcriptomic effects of PpIX, microarray analyses were conducted using HeLa cells with limited proliferation capacity. Based on the p-values (p < 0.01), we selected genes showing altered expression in each treatment group with reference to the non-treatment (NT) group. We detected 290, 196 and 28 upregulated genes, as well as 203, 146 and 36 downregulated genes after a 6 h-long PpIX treatment (1 μg/mL) prior to 3 Gy X-ray irradiation (PpIX-XT), 3 Gy X-ray irradiation alone (XT) and PpIX treatment alone (PpIXT), respectively. Functional analysis revealed that a majority of the regulated genes in the XT and PpIX-XT groups were related to cell-cycle arrest. The XT and PpIX-XT groups differed in the quantity, but not in the quality of their gene expression. The combined effect of PpIX and X-ray irradiation sensitized HeLa cells to X-ray treatment.

    DOI PubMed

  • The measurement of the cedar allergen in the indoor-outdoor atmosphere against the particle size and the media performance evaluation with the micro cedar pollen

    片山 秀夫, 高橋 淳子, 岸本 敏始

    空気清浄 : コンタミネーションコントロール   52 ( 3 ) 201 - 211  2014

    CiNii

  • 5-Aminolevulinic acid enhances cancer radiotherapy in a mouse tumor model

    Junko Takahashi, Masaki Misawa, Mami Murakami, Takashi Mori, Kazuki Nomura, Hitoshi Iwahashi

    SPRINGERPLUS   2  2013  [Refereed]

    Authorship:Lead author, Corresponding author

     View Summary

    5-Aminolevulinic acid (ALA) is a photosensitizer used in photodynamic therapy (PDT) because it causes preferential accumulation of protoporphyrin IX (PpIX) in tumor cells, where it forms singlet oxygen upon light irradiation and kills the tumor cells. Our previous study demonstrated that PpIX enhances generation of reactive oxygen species by physicochemical interaction with X-rays. We investigated the effect of ALA administration with X-ray irradiation of mouse B16-BL6 melanoma cells in vitro and in vivo. ALA facilitates PpIX accumulation in tumor cells and enhances ROS generation in vitro. Tumor suppression significantly improved in animals treated with fractionated doses of radiation (3 Gy x 10; total, 30 Gy) with local administration of 50 mg/kg ALA at 24 h prior to fractional irradiation. These results suggest ALA may improve the efficacy of cancer radiotherapy by acting as a radiomediator.

    DOI

    Scopus

    37
    Citation
    (Scopus)
  • Oligonucleotide Microarray Analysis of Dietary-Induced Hyperlipidemia Gene Expression Profiles in Miniature Pigs

    Junko Takahashi, Shiori Waki, Rena Matsumoto, Junji Odake, Takayuki Miyaji, Junichi Tottori, Takehiro Iwanaga, Hitoshi Iwahashi

    PLOS ONE   7 ( 5 )  2012.05  [Refereed]

    Authorship:Lead author, Corresponding author

     View Summary

    Background: Hyperlipidemia animal models have been established, but complete gene expression profiles of the transition from normal lipid levels have not been obtained. Miniature pigs are useful model animals for gene expression studies on dietary-induced hyperlipidemia because they have a similar anatomy and digestive physiology to humans, and blood samples can be obtained from them repeatedly.
    Methodology: Two typical dietary treatments were used for dietary-induced hyperlipidemia models, by using specific pathogen-free (SPF) Clawn miniature pigs. One was a high-fat and high-cholesterol diet (HFCD) and the other was a high-fat, high-cholesterol, and high-sucrose diet (HFCSD). Microarray analyses were conducted from whole blood samples during the dietary period and from white blood cells at the end of the dietary period to evaluate the transition of expression profiles of the two dietary models.
    Principal Findings: Variations in whole blood gene expression intensity within the HFCD or the HFCSD group were in the same range as the controls provide with normal diet at all periods. This indicates uniformity of dietary-induced hyperlipidemia for our dietary protocols. Gene ontology-(GO) based functional analyses revealed that characteristics of the common changes between HFCD and HFCSD were involved in inflammatory responses and reproduction. The correlation coefficient between whole blood and white blood cell expression profiles at 27 weeks with the HFCSD diet was significantly lower than that of the control and HFCD diet groups. This may be due to the effects of RNA originating from the tissues and/or organs.
    Conclusions: No statistically significant differences in fasting plasma lipids and glucose levels between the HFCD and HFCSD groups were observed. However, blood RNA analyses revealed different characteristics corresponding to the dietary protocols. In this study, whole blood RNA analyses proved to be a useful tool to evaluate transitions in dietary-induced hyperlipidemia gene expression profiles in miniature pigs.

    DOI

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    7
    Citation
    (Scopus)
  • Whole Blood RNA analysis, Aging andDesease

    Takahashi, J, Takatsu, A, Misawa, M, Iwahashi, H

    Blood Cell - An Overview of Studies in Hematology   6   DOI:10.5772/48226  2012  [Refereed]  [Invited]

    Authorship:Lead author, Corresponding author

  • Generation of reactive oxygen species induced by gold nanoparticles under x-ray and UV Irradiations

    Masaki Misawa, Junko Takahashi

    NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE   7 ( 5 ) 604 - 614  2011.10  [Refereed]

     View Summary

    The radiosensitizing effect of 5-250 nm diameter Au nanoparticles (AuNPs) in water was investigated under irradiations of diagnostic x-ray and UV light. Enhanced generations of hydroxyl radical ((center dot)OH) and superoxide anion (O(2)(-)) were confirmed from their dependencies on the absorbed energy, ethanol concentration and AuNPs&apos; concentration. Two kinds of fluorescent probes revealed that the reactive oxygen species (ROS) generation rate under x-ray irradiation was enhanced by factors of 1.46 for (center dot)OH and 7.68 for O(2)(-). Photo-and Auger electron charge transfer is possibly relevant to generation of O(2)(-) near the particle surface, whereas fluorescent x-rays are involved in generation of (center dot)OH in the secondary water radiolysis. Smaller diameter AuNPs with larger surface area showed a greater yield of ROS. An inverse proportion of ROS generation to the AuNPs&apos; diameter suggests a catalytic function of AuNPs&apos; surface for enhanced ROS generation.
    From the Clinical Editor: This paper investigates the effects of UV and X-ray irradiation on reactive oxygen species induction of gold nanoparticles, concluding that smaller diameter AuNPs with larger surface area lead to a greater yield of ROS probably due to catalytic effects. The paper may be important for the development of novel non-toxic radiation sensitizers. (C) 2011 Elsevier Inc. All rights reserved.

    DOI

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    288
    Citation
    (Scopus)
  • Oligonucleotide Microarray Analysis of Age-Related Gene Expression Profiles in Miniature Pigs

    Junko Takahashi, Masaki Misawa, Hitoshi Iwahashi

    PLOS ONE   6 ( 5 )  2011.05  [Refereed]

    Authorship:Lead author, Corresponding author

     View Summary

    Miniature pigs are useful model animals for humans because they have similar anatomy and digestive physiology to humans and are easy to breed and handle. In this study, whole blood microarray analyses were conducted to evaluate variations of correlation among individuals and ages using specific pathogen-free (SPF) Clawn miniature pigs. Whole blood RNA is easy to handle compared to isolated white blood cell RNA and can be used for health and disease monitoring and animal control. In addition, whole blood is a heterogeneous mixture of subpopulation cells. Once a great change occurs in composition and expressing condition of subpopulations, their associated change will be reflected on whole blood RNA. From 12 to 30 weeks of age, fractions of lymphocytes, monocytes, neutrophils, eosinophils, and basophils in white blood cells showed insignificant differences with age as a result of ANOVA analysis. This study attempted to identify characteristics of age-related gene expression by taking into account the change in the number of expressed genes by age and similarities of gene expression intensity between individuals. As a result, the number of expressed genes was less in fetal stage and infancy period but increased with age, reaching a steady state of gene expression after 20 weeks of age. Variation in gene expression intensity within the same age was great in fetal stage and infancy period, but converged with age. The variation between 20 and 30 weeks of age was comparable to that among 30 weeks individuals. These results indicate that uniformity of laboratory animals is expected for miniature pigs after 20 weeks of age. Furthermore, a possibility was shown that whole blood RNA analysis is applicable to evaluation of physiological state.

    DOI

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    6
    Citation
    (Scopus)
  • 連続的疲労負荷過程における血液中で発現する生理的疲労関連遺伝子の検討

    原田 暢善, 岩木 直, 高橋 淳子, 岩橋 均

    日本疲労学会誌   6 ( 2 ) 28 - 35  2011

  • Characterization of reactive oxygen species generated by protoporphyrin IX under X-ray irradiation

    Junko Takahashi, Masaki Misawa

    RADIATION PHYSICS AND CHEMISTRY   78 ( 11 ) 889 - 898  2009.11  [Refereed]

    Authorship:Lead author

     View Summary

    As a possible radiosensitizer candidate having biological compatibility, oncotropic property, and X-ray activation capability, contribution of protoporphyrin IX (PpIX) to enhanced generation of reactive oxygen species (ROS) under X-ray and UV irradiations were examined. To identify the kinds of ROS, 2-[6-(4-amino)phenoxy-3H-xanthen-3-on-9-yl] benzoic acid (APF) and dihydroethidium (DHE) were used together with ethanol as a hydroxyl radical (OH(center dot)) quencher. All of the three species of our interest (OH(center dot), superoxide radical (O(2)(center dot-)), and singlet oxygen ((1)O(2))) were enhanced by PpIX under X-ray and UV irradiations in addition to those by radiolysis and photolysis. Its enhancement factors exceeded 1.7 depending on the concentrations of PpIX from 1.5 to 15.0 mu g/ml. (C) 2009 Elsevier Ltd. All rights reserved.

    DOI

    Scopus

    45
    Citation
    (Scopus)
  • Proposal of Standard Microorganisms for Standardization of High Pressure Food Technology

    Iwahashi Hitoshi, Harada Nobuyoshi, Misawa Masaki, Takahashi Junko, Obuchi Kaoru, Yamamoto Kazutaka, Sasagawa Akihiko, Kobayashi Atsushi, Yamazaki Akira

    High Pressure Bioscience and Biotechnology   2 ( 1 ) 122 - 129  2008

     View Summary

    The research field of high pressure processed food technology was spread from basic science to commercial basis progress. Thus, this technology is being accepted by consumer and is now on the stage of standardization. Standardization is required for the stable and safety supply of high pressure processed food to consumer. In this paper, we would like to suggest the draft version of &quot;Technical Report&quot; concern to indicative standard microorganisms using yeast, &lt;I&gt;Saccharomyces cerevisiae&lt;/I&gt;. We selected the strain of S288C, medium of YPD, and cultivation time of 50-150h at 25°C. The strain was selected as the genome sequence of this strain was already analyzed and thus the most characterized strain in the yeast strains. YPD medium is widely used by basic scientist and applied scientist. The cultivation time was examined by counting CFU after and before pressure treatment and we found yeast cells during this growth phase showed the reproducible high pressure resistance. Next step is the validation studies of this &quot;Technical Report&quot; in different laboratories. We would like to call for participation in the validation studies to laboratories.

    CiNii

  • Analysis of potential radiosensitizing materials for x-ray-induced photodynamic therapy

    Junko Takahashi, Masaki Misawa

    Nanobiotechnology   3 ( 2 ) 116 - 126  2007.05  [Refereed]

    Authorship:Lead author

     View Summary

    For a development of deep tumor treatment in photodynamic therapy, a feasibility of novel radiosensitizers induced by x-ray was investigated. The sensitizers are designed to generate reactive oxygen species (ROS) inside or outside the cell, possibly leading to damage exclusively on tumor cells and reservation of normal cells along the x-ray path. Taking note of the similarity in energy transfer mechanism in photocatalysts, scintillators, and particulate semiconductors, we chose TiO2, ZnS:Ag, CeF3, and quantum dots (CdTe and CdSe) in particulate form, which contain heavy atoms for efficient absorption of x-rays. A parameter study for x-ray operating conditions showed that in a typical scenario, photons with 20 to 170 keV energy are attenuated by 90% through the region of particle dispersed aqueous solution at varying concentration between 0.01 and 100 wt%. The amount of ROS generation under the exposure of polychromatic x-ray was measured using dihydroethidium reagent which detects an integrated amount of several species. Proportional increase in ROS generation to x-ray dose was observed for varying concentrations of TiO2, ZnS:Ag, CeF3, and CdSe quantum dot dispersions. Then, HeLa cells were mixed with aqueous solutions dispersed with sensitizing materials at a concentration of 3.0 mg/ml and were exposed to x-ray. Their survival fraction obtained by a cell proliferation reagent WST-1 immediately after the irradiation showed insignificant effects of sensitizing materials except at large doses. To enhance the sensitization effect, bio-conjugated CdSe quantum dots were internalized in the cytoplasm up to a concentration of 1.0 ng/ml. The cells were irradiated by x-ray up to 5 Gy, and their survival fraction was measured by the colony forming ability 9 days after irradiation. Survival fraction of the cells treated with quantum dots were less than those without quantum dots for all doses, suggesting that the colony forming ability is impaired by the internalized quantum dots. © 2008 Humana Press Inc.

    DOI

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    50
    Citation
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  • Flexible manipulation of microfluids using optically regulated adsorption/desorption of hydrophobic materials

    Hidenori Nagai, Takashi Irie, Junko Takahashi, Shin-ichi Wakida

    BIOSENSORS & BIOELECTRONICS   22 ( 9-10 ) 1968 - 1973  2007.04  [Refereed]

     View Summary

    To realize highly integrated micro total analysis systems (mu TAS), a simply controlled miniaturized valve should be utilized on microfluidic device. In this paper, we describe the application of photo-induced super-hydrophilicity of titanium dioxide (TiO2) to microfluidic manipulation. In addition, we found a new phenomenon for reversibly converting the surface wettability using a polydimethylsiloxane (PDMS) matrix and the photocatalytic properties of TiO2. While PDMS polymer was irradiated with UV, it was confirmed that hydrophobic material was released from the polymer to air. Several prepolymers were identified as the hydrophobic material with a gas chromatograph and mass spectrometer (GUMS). Here, we successfully demonstrated the flexible manipulation of microfluid in a branched microchannel using the reversible wettability as micro opto-switching valve (MOS/V). The simultaneous control of MOS/Vs was also demonstrated on a 256-MOS/V integrated disk. The MOS/V promises to be one of the most effective flow switching valves for advanced applications in highly integrated micro/nano fluidics. (c) 2006 Elsevier B.V. All rights reserved.

    DOI

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    36
    Citation
    (Scopus)
  • Response of Saccharomyces cerevisiae to a monoterpene: evaluation of antifungal potential by DNA microarray analysis

    M Parveen, MK Hasan, J Takahashi, Y Murata, E Kitagawa, O Kodama, H Iwahashi

    JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY   54 ( 1 ) 46 - 55  2004.07  [Refereed]

     View Summary

    Plant-derived essential oils with monoterpenoids have been used as antifungal drugs since ancient times, but the mode of action of these natural hydrocarbons at the molecular level is not understood. In order to understand the mechanisms of toxicity of alpha-terpinene (a cyclic monoterpene), a culture of Saccharomyces cerevisiae was exposed to 0.02% alpha-terpinene for 2 h and transcript profiles were obtained using yeast DNA arrays. These profiles, when compared with transcript profiles of untreated cultures, revealed that the expression of 793 genes was affected. For 435 genes, mRNA levels in treated cells compared with control cells differed by more than two-fold, whereas for 358 genes, it was &lt;0.5-fold. Northern blots were performed for selected genes to verify the microarray results. Functional analysis of the up-regulated genes indicates that, similar to commonly used antifungal drugs, alpha-terpinene exposure affected genes involved in ergosterol biosynthesis and sterol uptake. In addition, transcriptional induction of genes related to lipid metabolism, cell wall structure and function, detoxification and cellular transport was observed in response to terpinene toxicity. Notably, the functions of 192 up-regulated genes are still unknown, but their characterization will probably shed light on the mechanisms of drug resistance and sensitivity. Taken together, this study showed that alpha-terpinene has strong antifungal activities and its modes of action resemble those of presently used antifungal drugs.

    DOI

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    101
    Citation
    (Scopus)
  • Multiple reporter gene assays for the assessment and estimation of chemical toxicity.

    Takahashi J, Iwahashi H

    Environ Sci   11 ( 5 ) 269 - 282  2004  [Refereed]

  • Effects of the pesticide thiuram: Genome-wide screening of indicator genes by yeast DNA microarray

    E Kitagawa, J Takahashi, Y Momose, H Iwahashi

    ENVIRONMENTAL SCIENCE & TECHNOLOGY   36 ( 18 ) 3908 - 3915  2002.09  [Refereed]

     View Summary

    Although there have been studies on the toxicity of the pesticide thiuram, the present study is the first one to attempt to integrate a whole genomic response using microarray technology. From the DNA microarray experiment, it was found that exposure to thiuram led to alterations of gene expression in yeast cells and that many genes involved in detoxification and stress response were highly induced. The induced genes were classified according to the MIPS yeast database. The induction of genes concerned with folding and proteolysis reflects the protein denaturing and degradation effects of the thiuram treatment. The induction of genes involved in redox and defense against reaction oxygen species also suggests that thiuram has other effects, such as oxidative stress. Genes classified for carbohydrate metabolism and energy were also highly induced, and these gene products may play the role of providing the energy for the detoxification mechanism. In addition, in view of the induction of some genes involved in DNA repair, thiuram potentially causes DNA damage. Therefore, as stated in previous reports, thiuram is a potential positive toxic chemical. On the other hand, YKL071W, YCR102C, YLR303W, and YLL057C were selected based on the result of a DNA microarray experiment and used for the promoter activity assay. Thiuram treatment affected the promoter of these genes, indicating that this technique could be used for the selection of biomarker candidates.

    DOI

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    46
    Citation
    (Scopus)
  • Measurement of the Lipid and Autofluorescence of Cholesterol-fed Guinea Pig Plasma

    TAKAHASHI J, SATO M

    脈管学   38 ( 11 ) 785 - 794  1998.11

    CiNii

  • Autofluorescence Analysis of Normal and Oxidized Human Plasma

    TAKAHASHI J, SATO M

    脈管学   38 ( 2 ) 109 - 116  1998.02

    CiNii

▼display all

Research Projects

  • Advancing Radiomodulator-Enhanced Radiation Therapy for Superior Tumor Control and Reduced Late Toxicity

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2024.04
    -
    2028.03
     

  • Development of immunoradiotherapy that integrates radiosensitization and immunostimulation

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2022.04
    -
    2026.03
     

  • 高い抗腫瘍効果と副作用軽減を同時に目指す新規放射線治療法

    日本学術振興会  科学研究費助成事業

    Project Year :

    2020.04
    -
    2023.03
     

    長澤 慎介, 高橋 淳子

     View Summary

    正常細胞に対する放射線防護能と腫瘍細胞に対する放射線増感能の両性質を持つと考えられる薬剤について、まず正常細胞に対する放射線防護能を確認およびその分子生物学的機序を探索するための研究を行っている。正常細胞についてはいくつかの種類に対し前述の内容を確認する予定だが、まずは比較的扱いの容易な線維芽細胞を対象にしている。薬剤曝露群と被曝露群とに分けそれぞれに放射線照射を行い、コロニー形成法を用いて細胞の生存曲線を描いた。細胞が十分なコロニーを形成していなければ細胞死しているとみなした。データについてはもう少し実験を繰り返す必要があるが、見込みとしては正常組織に対する照射の影響は少なくなるのではないかと考えられる。
    ただし上記実験を行っていた途中で放射線照射装置が故障し、9か月程度の実験進捗の停滞を余儀なくされてしまった。現在は修理を終えたところだが、放射線の線量率や線量分布などが変化している可能性があり、装置の性能の検証も含めて実験データを取り直す必要が生じる恐れがある。まずはパイロット実験を再度行って検証する方針としているが、もしそのパイロット実験結果が当初のものと異なっている場合は、当初の予定に比べ大幅な実験計画の練り直しが必要になるだろう。
    他、研究を進める過程で放射線に対する細胞の反応について新しい知見が得られてきている。これらについては文献収集など含めて解析し、適宜発表する予定としている。

  • Basic research for clinical application of 5-aminolevulinic acid radiodynamic therapy

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2018.04
    -
    2023.03
     

  • Basic research on the radiation response of small molecule organic compounds at low concentrations by low dose X-ray irradiation

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2019.06
    -
    2022.03
     

    Takahashi Junko

     View Summary

    Protoporphyrin IX (PpIX), which selectively accumulates in cancer cells by administration of 5-aminolevulinic acid, enhances the production of reactive oxygen species (ROS) by X-ray irradiation and functions as a radiosensitizer in radiotherapy.
    The purpose of this study is to investigate the X-ray responsiveness of small molecule organic compounds other than PpIX. We verified the integrity of our methodology using ROS detection probe reactions in X-ray irradiation. We investigated the X-ray responsiveness and cytotoxicity of sensitizer candidate substances. In addition, we evaluate DNA strand break properties of PpIX by X-ray irradiation. As a result, various kinds of small molecule organic compounds show X-ray responsiveness and radiosensitizing effect. Evaluation using derivatives also suggested that the radiation responsiveness of organic compounds is related to the molecular structure.

  • Elucidation of the action mechanism of combined treatment with X-ray irradiation and 5-aminolevulinic acid by trantcriptome analysis

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2013.04
    -
    2018.03
     

    Takahashi Junko

     View Summary

    Combined treatment with 5-aminolevulinic acid (ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from ALA enhances the generation of ROS by the X-ray irradiation. In the present study, a high-energy medical linear accelerator was used instead of a non-medical low energy X-ray irradiator, which had been previously used. Tumor-bearing mice implanted with B16-BL6 melanoma cells were treated with fractionated doses of irradiation (in total, 20 or 30 Gy), using two types of X-ray irradiator after ALA administration. Suppression of tumor growth was enhanced with X-ray irradiation in combination with ALA treatment compared with X-ray treatment alone, using both medical and non-medical X-ray irradiators. “Radiodynamic therapy” using radiation from medical linacs as a physical driving force, rather than the light used in photodynamic therapy, may have potential clinical applications.

  • Essential trial to achieve blood RNA diagnosis based on gene expression profiles

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2013.04
    -
    2016.03
     

    Takahashi Junko, IWAHASHI Hitoshi

     View Summary

    Now, the RNA diagnosis requires standardization of procedure for making reproducible samples.In blood, we may find huge information concern to physiological conditions of organ and tissue, in addition to function of RNAs. These technologies can be achieved owing to next-generation DNA sequencer. To support those technologies, we studied the evaluation procedures for quality of prepared RNA and for identification of original organ in blood RNA.

  • A fundamental study of the porphyrins as radiosensitizing materials for X-ray

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2010
    -
    2012
     

    TAKAHASHI Junko, MISAWA Masaki, IWAHASHI Hitoshi

     View Summary

    Radiotherapy damages normal and cancerous cells, causing treatment-related side effects. To control and limit irradiation to tumor cells while sparing normal cells, we must develop methods to enhance dosing precision. 5-Aminolevulinic acid (5-ALA) is a ph

  • 低エネルギーX線による金ナノ粒子活性化とエネルギー伝達機構に関する研究

    日本学術振興会  科学研究費助成事業

    Project Year :

    2011
     
     
     

    三澤 雅樹, 高橋 淳子

     View Summary

    腫瘍細胞の標的部位に集積する機能を付与した金ナノ粒子をX線治療用増感剤として用いることで、深部・大容積のがん治療に役立つX線光線力学的治療(XPDT)を提案した。H23は、1)X線エネルギー伝達計測、2)エネルギー変換メカニズム解析、3)活性酸素種発生量計測を行った。また、H24に予定していた4)腫瘍集積性のバイオコンジュゲート合成、5)in vitro腫瘍細胞影響評価に加え、6)in vivoの予備実験を前倒しで実施した。その結果、以下の結果が得られた。
    ・エネルギー変換メカニズムと活性酸素種の測定
    金ナノ粒子によって吸収されたX線の一部は、光電効果により電子を発生させ、周囲の酸素を還元し、反応性の高い活性酸素を発生する。その結果、一重項酸素、スーパーオキシド、ヒドロキシラジカルが発生していることがわかった。
    ・バイオコンジュゲート合成
    腫瘍集積性を高めるために、腫瘍細胞に高発現するトランスフェリン、EGFR、TRALなどで修飾したカチオン性脂質やリポソームを用い、細胞内に金ナノ粒子複合体を導入した。一次抗体として、ミトコンドリア等に高発現しているVDAC1、COX4を結合させ、金ナノ粒子をミトコンドリア近傍に送達する複合体を合成した。
    ・in vitroおよびin vivo腫瘍細胞影響評価
    合成した金ナノ粒子複合体を、HeLa細胞に投与し、X線照射下で生存率を調べた結果、15GyのX線照射下で1.4nmの金ナノ粒子複合体投与群で、有意に細胞生存率が低下した。in vivoではB16の黒色メラノーマ担がんマウスに投与し、30GyのX線照射下で、金ナノ粒子投与群で、腫瘍体積増加率が有意に減少することを確認した。
    以上のことから、金ナノ粒子複合体がX線治療の増感剤として有効であり、XPDTの確立に必要なX線条件および細胞内送達方法等の基本要件が明らかになった。

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Misc

  • 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

    CiNii

  • 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

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    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.

    CiNii

Industrial Property Rights

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Sub-affiliation

  • Faculty of Science and Engineering   School of Fundamental Science and Engineering

Research Institute

  • 2022
    -
    2024

    Waseda Research Institute for Science and Engineering   Concurrent Researcher

Internal Special Research Projects

  • X線照射により活性酸素を生じる放射線増感剤に関する研究

    2023  

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    プロトポルフィリンIX(PpIX)前駆体である5-アミノレブリン酸(5-ALA)は、生体に取り込まると腫瘍細胞に特異的にPpIXが蓄積することが知られている。PpIXおよびその誘導体に光を照射すると、光化学反応により蛍光や活性酸素が生じる。この蛍光を利用して腫瘍範囲を特定する「光線力学診断法(Photodynamic Diagnosis)」、また活性酸素の細胞損傷効果を利用した「光線力学療法(Photodynamic Therapy)」が、がん治療法に用いられつつある。一方、PpIXにX線を照射すると活性酸素の生成が増強されることをこれまでに見いだした。PpIXとX線の反応は光による光化学反応に類似しており、光の届かない深部のがんの放射線治療をより効果的に行う「放射線力学療法(Radiodynamic Therapy) 」の可能性を示すものであった。そこでこれまでに、PpIXにより生じる活性酸素種の特定、細胞損傷効果(in vitro試験)、担癌動物を用いた治療効果(in vivo試験)等を行ってきた。しかし、PpIXは化学式C34H34N4O4、分子量562.7の低分子有機化合物でありこの様な有機化合物とX線の物理化学反応に関する研究は殆ど無く、その反応の詳細は未だ不明である。そこで、本課題では基礎的研究を進める為に、PpIX以外の様々な低分子有機化合物のX線に対する応答を、活性酸素種に特異的な活性酸素検出指示薬を用いて評価した。その結果、数種類の腫瘍親和性を有する有機化合物がPpIXと同様の応答をするという結果が得られた。