Updated on 2022/03/31


Graduate School of Medicine Center for Research of Laboratory Animals and Medical Research Engineering Division for Advanced Medical Research Assistant Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Assistant Professor
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Degree 1

  1. 学士(医学) ( 2012.3   熊本大学 ) 

Research Interests 4

  1. Carcinogenesis

  2. Ovarian cancer

  3. フェロトーシス

Research Areas 2

  1. Life Science / Obstetrics and gynecology  / gynecological cancer

  2. Life Science / Experimental pathology  / Pathology

Current Research Project and SDGs 4

  1. 細胞外微粒子への生体応答と発がん・動脈硬化症との関連の解析

  2. 環境中に存在するタルク、アスベストによる、卵巣がん形成機序の解明

  3. 新規ナノマテリアルのリスク評価

  4. アスベストおよびタルクが タンパク質を吸着することで惹起する、 卵巣におけるcancer initiating eventsの解明

Awards 1

  1. Discussant賞

    2021.2   第141会東海産科婦人科学会  

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    Award type:Award from Japanese society, conference, symposium, etc. 


Papers 11

  1. Double-edged Sword Role of Iron-loaded Ferritin in Extracellular Vesicles

    Toyokuni Shinya, Kong Yingyi, Zheng Hao, Mi Danyang, Katabuchi Misako, Motooka Yashiro, Ito Fumiya

    JOURNAL OF CANCER PREVENTION   Vol. 26 ( 4 ) page: 244 - 249   2021.12

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  2. Role of ferroptosis in nanofiber-induced carcinogenesis

    Toyokuni Shinya, Ito Fumiya, Motooka Yashiro

    Metallomics Research   Vol. 1 ( 1 ) page: rev-14 - rev-21   2021.10

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    Language:English   Publisher:Japan Society for Biomedical Research on Trace Elements  

    <p>Biopersistent nanofibers with specified physical dimension are unexpected human carcinogens whether they are natural or synthetic. Asbestos, a natural fibrous mineral, is classified as a definite human carcinogen (IARC Group 1) to cause malignant mesothelioma (MM) and lung cancer. Multi-walled carbon nanotube of 50 nm-diameter was defined in 2014 as a possible carcinogen (IARC Group 2B) toward MM, fortunately with no authorized patients thus far. Carcinogenic mechanism of asbestos has been a mystery for a long time. It is now recognized that asbestos goes through lung parenchyma by collecting hemoglobin-derived iron to reach pleural cavity, which takes several decades. Iron-loaded asbestos can induce oxidative damage directly to mesothelial cells, carcinogenesis-target cells lining somatic cavities. Recently, it was clarified that surrounding stromal environment are as important for mesothelial carcinogenesis. The novel concept here is ceaseless ferroptosis of macrophages, which forms a Fe(II)-dependent stromal mutagenic milieu indirectly for mesothelial cells and indeed is a revised understanding of frustrated phagocytosis. Deposition of foreign materials eventually causes iron accumulation <i>in situ</i> due to the innate characteristic of preserving iron inside cells. Nanofiber-induced carcinogenesis may be involved in other human carcinogenesis, including ovarian cancer. Alternatively, iron excess can be an optimal target of cancer prevention and cancer treatment. </p>

    DOI: 10.11299/metallomicsresearch.mr202102

    CiNii Research

  3. Plasma-activated Ringer's lactate solution inhibits the cellular respiratory system in HeLa cells

    Tanaka Hiromasa, Maeda Shogo, Nakamura Kae, Hashizume Hiroshi, Ishikawa Kenji, Ito Mikako, Ohno Kinji, Mizuno Masaaki, Motooka Yashiro, Okazaki Yasumasa, Toyokuni Shinya, Kajiyama Hiroaki, Kikkawa Fumitaka, Hori Masaru

    PLASMA PROCESSES AND POLYMERS   Vol. 18 ( 10 )   2021.10

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    Language:Japanese   Publisher:Plasma Processes and Polymers  

    Nonequilibrium atmospheric pressure plasma has enabled a variety of new applications in medicine, agriculture, and other industries. It is particularly noteworthy that plasma itself and/or plasma-activated culture medium have been shown to preferentially kill various cancer cells. We have previously developed a plasma-activated Ringer's lactate solution (PAL) for use as a new cancer treatment. In this study, behaviors of extracellular and intracellular reactive oxygen and nitrogen species in the cellular respiratory system of PAL-treated HeLa cells were investigated using an extracellular flux analyzer and a probe to measure mitochondrial membrane potential. In PAL-treated HeLa cells, extracellular hydrogen peroxide in PAL was found to be responsible for the induction of intracellular hydrogen peroxide and apoptosis, while other components in PAL are responsible for the induction of non-H2O2 intracellular ROS and non-apoptotic cell death, which should be clarified by further experiments. We believe that these are long-lived species derived from plasma-activated lactates. Furthermore, we found that the plasma-activated lactates inhibited glycolysis and the tricarboxylic acid (TCA) cycle, but not the electron transport chain in HeLa cells. These results suggest that PAL induces multiple modes of cell death, including apoptosis through hydrogen peroxide, and non-apoptotic cell death associated with the impairment of mitochondrial functions (glycolysis and TCA cycle). These findings shed light on the novel mechanism underlying plasma-activated lactate-induced cell death.

    DOI: 10.1002/ppap.202100056

    Web of Science


  4. Role of ferroptosis in nanofiber-induced carcinogenesis Invited Reviewed

    Shinya Toyokuni, Fumiya Ito, Yashiro Motooka

    Metallomics Research   Vol. 1   page: 14 - 21   2021

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    Authorship:Last author   Language:English  

  5. Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice

    Hayashi Shotaro, Nakamura Tomoko, Motooka Yashiro, Ito Fumiya, Jiang Li, Akatsuka Shinya, Iwase Akira, Kajiyama Hiroaki, Kikkawa Fumitaka, Toyokuni Shinya

    REDOX BIOLOGY   Vol. 37   page: 101726   2020.10

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    Language:Japanese   Publisher:Redox Biology  

    Ovarian endometriosis (OE) provides women of reproductive age with not only severe menstrual pain but also infertility and an increased risk for ovarian carcinogenesis. Whereas peritoneal endometriosis models have been developed with syngeneic implantation of minced uterine tissue and oncogenic K-ras allele with conditional Pten deletion within ovarian surface epithelium generated preneoplastic endometrial glandular morphology, followed by endometrioid adenocarcinoma, there has been no mouse model of OE similar to human counterparts, applicable to preclinical studies. Here we for the first time established a murine OE model that reveals infertility, and evaluated the involvement of iron catalyzed oxidative stress in the pathogenesis. Minced uterine tissue from female mice was implanted on ovarian surface of syngeneic mice after bursectomy to induce OE. Ectopic growth of endometrium was observed in association with ovary 4 weeks after implantation in 85.7% (12/14) of the operated mice with our protocol. Endometriotic lesions involved intestine, pancreas and peritoneal wall. Fibrosis around the ovary was prominent and increased time-dependently in the OE group. Iron accumulation was significantly increased in the OE group, leading to oxidative stress in each stage of the follicles as evaluated by 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2′-deoxyguanosine. Expression of follicle stimulating hormone receptor in the follicles revealed a significant decrease during pre-antral, antral and pre-ovulatory phases in the OE group. Finally, the number of pups was significantly reduced in the OE group in comparison to the controls. This model affords an opportunity to evaluate agents or procedures to counteract ovarian endometriosis in the preclinical settings.

    DOI: 10.1016/j.redox.2020.101726

    Web of Science



  6. Connective tissue growth factor produced by cancer-associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma

    Ohara Yuuki, Enomoto Atsushi, Tsuyuki Yuta, Sato Kotaro, Iida Tadashi, Kobayashi Hiroki, Mizutani Yasuyuki, Miyai Yuki, Hara Akitoshi, Mii Shinji, Suzuki Jun, Yamashita Kyoko, Ito Fumiya, Motooka Yashiro, Misawa Nobuaki, Fukui Takayuki, Kawaguchi Koji, Yokoi Kohei, Toyokuni Shinya

    ONCOLOGY REPORTS   Vol. 44 ( 3 ) page: 838 - 848   2020.9

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    Language:Japanese   Publisher:Oncology Reports  

    Malignant mesothelioma is an aggressive neoplasm for which effective treatments are lacking. We often encounter mesothelioma cases with a profound desmoplastic reaction, suggesting the involvement of cancer.associated fibroblasts (CAFs) in mesothelioma progression. While the roles of CAFs have been extensively studied in other tumors and have led to the view that the cancer stroma contains heterogeneous populations of CAFs, their roles in mesothelioma remain unknown. We previously showed that connective tissue growth factor (CTGF), a secreted protein, is produced by both mesothelioma cells and fibroblasts and promotes the invasion of mesothelioma cells in vitro. In this study, we examined the clinical relevance of CAFs in mesothelioma. Using surgical specimens of epithelioid malignant pleural mesothelioma, we evaluated the clinicopathological significance of the expression of α-smooth muscle actin (αSMA), the most widely used marker of CAFs, the expression of CTGF, and the extent of fibrosis by immunohistochemistry and Elastica.Masson staining. We also analyzed the expression of mesenchymal stromal cell. and fibroblast.expressing Linx paralogue (Meflin; ISLR), a recently reported CAF marker that labels cancer.restraining CAFs and differ from αSMA-positive CAFs, by in situ hybridization. The extent of fibrosis and CTGF expression in mesothelioma cells did not correlate with patient prognosis. However, the expression of αSMA and CTGF, but not Meflin, in CAFs correlated with poor prognosis. The data suggest that CTGF+ CAFs are involved in mesothelioma progression and represent a potential molecular target for mesothelioma therapy.

    DOI: 10.3892/or.2020.7669

    Web of Science



  7. Ferroptosis at the crossroads of infection, aging and cancer

    Toyokuni Shinya, Yanatori Izumi, Kong Yingyi, Zheng Hao, Motooka Yashiro, Jiang Li

    CANCER SCIENCE   Vol. 111 ( 8 ) page: 2665 - 2671   2020.8

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    Language:Japanese   Publisher:Cancer Science  

    Despite significant developments and persistent efforts by scientists, cancer is one of the primary causes of human death worldwide. No form of life on Earth can survive without iron, although some species can live without oxygen. Iron presents a double-edged sword. Excess iron is a risk for carcinogenesis, while its deficiency causes anemia, leading to oxygen shortage. Every cell is eventually destined to death, either through apoptosis or necrosis. Regulated necrosis is recognized in distinct forms. Ferroptosis is defined as catalytic Fe(II)-dependent regulated necrosis accompanied by lipid peroxidation. The main observation was necrosis of fibrosarcoma cells through inhibition of cystine/glutamate antiporter with erastin, which reduced intracellular cysteine and, thus, glutathione levels. Our current understanding of ferroptosis is relative abundance of iron (catalytic Fe[II]) in comparison with sulfur (sulfhydryls). Thus, either excess iron or sulfur deficiency causes ferroptosis. Cell proliferation inevitably requires iron for DNA synthesis and energy production. Carcinogenesis is a process toward iron addiction with ferroptosis resistance. Conversely, ferroptosis is associated with aging and neurodegeneration. Ferroptosis of immune cells during infection is advantageous for infectious agents, whereas ferroptosis resistance incubates carcinogenic soil as excess iron. Cancer cells are rich in catalytic Fe(II). Directing established cancer cells to ferroptosis is a novel strategy for discovering cancer therapies. Appropriate iron regulation could be a tactic to reduce and delay carcinogenesis.

    DOI: 10.1111/cas.14496

    Web of Science



  8. Connective tissue growth factor produced by cancer-associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma. Reviewed

    Yuuki Ohara, Atsushi Enomoto, Yuta Tsuyuki, Kotaro Sato, Tadashi Iida, Hiroki Kobayashi, Yasuyuki Mizutani, Yuki Miyai, Akitoshi Hara, Shinji Mii, Jun Suzuki, Kyoko Yamashita, Fumiya Ito, Yashiro Motooka, Nobuaki Misawa, Takayuki Fukui, Koji Kawaguchi, Kohei Yokoi, Shinya Toyokuni

    Oncology Report   Vol. 44 ( 3 ) page: 838 - 848   2020

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  9. Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice. Invited Reviewed

    Shotaro Hayashi, Tomoko Nakamura, Yashiro Motooka, Fumiya Ito, Li Jiang, Shinya Akatsuka, Akira Iwase, Hiroaki Kajiyama, Fumitaka Kikkawa, Shinya Toyokuni.

    Redox Biology   Vol. 37   page: 101726   2020

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

  10. Ferroptosis at the crossroads of infection, aging and cancer Reviewed

    Shinya Toyokuni, Izumi Yanatori, Yingyi Kong, Hao Zheng, Yashiro Motooka, Li Jiang

    Cancer science   Vol. 111 ( 8 ) page: 2665 - 2671   2020

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

  11. Non-thermal plasma specifically kills oral squamous cell carcinoma cells in a catalytic Fe(II)-dependent manner. Reviewed

    Kotaro Sato, Lei Shi, Fumiya Ito, Yuuki Ohara, Yashiro Motooka, Hiromasa Tanaka, Masaaki Mizuno, Masaru Hori, Tasuku Hirayama, Hideharu Hibi, Shinya Toyokuni

    Journal of Clinical Biochemistry and Nutrition   Vol. 65 ( 1 ) page: 8 - 15   2019

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Books 2

  1. マウス・ラット モデル作成・解析プロフェッショナル

    豊國伸哉, 伊藤文哉, 本岡 大社, 蒋麗( Role: Contributor ,  第2章7節 使いたくなる病理解析新技術)

    羊土社  2021.4 

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    Total pages:317   Responsible for pages:147-160   Language:Japanese

  2. 図解腫瘍薬学

    本原剛志、本岡大社、三宅俊介、片渕秀隆、城野博史( Role: Contributor ,  13章臓器別がん薬物療法 7)生殖器がん①(卵巣がん、子宮頸がん、子宮体がん))

    南山堂  2020.7 

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    Language:Japanese Book type:Textbook, survey, introduction

Presentations 3

  1. アスベストとタルクは鉄代謝異常による 酸化ストレスの増加から卵巣発がんに関与する

    本岡 大社、豊國 伸哉

    レドックスR&D戦略委員会 第1回若手シンポジウム  2021.11.8  熊本大学微生物学講座

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    Event date: 2021.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:web   Country:Japan  

  2. Iron overload led by genital talc exposure contributes to ovarian carcinogenesis

    Yashiro Motooka, Fumiya Ito, Hironori Tashiro, Hidetaka Katabuchi, Shinya Toyokunii


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    Event date: 2021.9 - 2021.10

    Language:English   Presentation type:Oral presentation (general)  


  3. Asbestos contributes to ovarian carcinogenesis Invited International conference

    Yashiro Motooka, Hironori Tashiro, Shinya Toyokuni, Hidetaka Katabuchi

    The 60th Annual Congress and The 9th International Symposium of the Taiwan Association of Obstetrics and Gynecology  2021.5.30  Taiwan Association of Obstetrics and Gynecology

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    Event date: 2021.5

    Language:English   Presentation type:Oral presentation (invited, special)  

    Venue:Taiwan   Country:Taiwan, Province of China  

Research Project for Joint Research, Competitive Funding, etc. 2

  1. タルクによるEVs伝達阻害:卵巣における評価と応用

    2022.4 - 2023.3

    令和4年度 CREST「細胞外微粒子」若手チャレンジ  

    本岡 大社

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    Grant type:Competitive

    Grant amount:\500000

  2. アスベストおよびタルクがタンパク質を吸着することで惹起する、卵巣におけるcancer initiating eventsの解明

    2021.4 - 2022.3

    令和3年度 CREST「細胞外微粒子」若手チャレンジ 


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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\1800000 ( Direct Cost: \1800000 )


Teaching Experience (On-campus) 3

  1. 基礎セミナー




  2. 病理学実習


  3. 基礎医学セミナー


Teaching Experience (Off-campus) 1

  1. 母性

    2015.4 - 2015.3

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    Level:Undergraduate (specialized)