Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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Ferroptosis in Cancer Research

Toyokuni Shinya

CANCER SCIENCE Vol. 109 page： 195-195 2018.12

Critical role of Hippo signaling pathway at the onset of squamous cell carcinomas

Suzuki Akira, Nishio Miki, Omori Hirofumi, To Yoko, Maehama Tomohiko, Aono Yukari, Kiyono Tohru, Taguchi Kenichi, Masuda Muneyuki, Toyokuni Shinya, Tashiro Hironori, Katabuchi Hidetaka

CANCER SCIENCE Vol. 109 page： 781-781 2018.12

Asbestos exposure as a possible cause of ovarian carcinogenesis

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

CANCER SCIENCE Vol. 109 page： 255-255 2018.12

Asbestos exposure as a possible cause of ovarian carcinogenesis International journal

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

CANCER SCIENCE Vol. 109 page： 255-255 2018.12

Analysis of the involvement of cancer-associated fibroblasts in the progression of malignant mesothelioma International journal

Ohara Yuuki, Enomoto Atsushi, Takahashi Masahide, Toyokuni Shinya

CANCER SCIENCE Vol. 109 page： 454-454 2018.12

Critical role of Hippo signaling pathway at the onset of squamous cell carcinomas International journal

Suzuki Akira, Nishio Miki, Omori Hirofumi, To Yoko, Maehama Tomohiko, Aono Yukari, Kiyono Tohru, Taguchi Kenichi, Masuda Muneyuki, Toyokuni Shinya, Tashiro Hironori, Katabuchi Hidetaka

CANCER SCIENCE Vol. 109 page： 781-781 2018.12

Inflammatory microenvironment derived from asbestos increases mutagenesis to repairing mesothelial cell International journal

Ito Fumiya, Toyokuni Shinya

CANCER SCIENCE Vol. 109 page： 830-830 - 830 2018.12

Ferroptosis in Cancer Research International journal

Toyokuni Shinya

CANCER SCIENCE Vol. 109 page： 195-195 2018.12

Multifaceted roles of Ptger2 (Prostaglandin E receptor 2) in asbestos-induced inflammation and malignant mesothelioma International journal

Jiang Li, Akatsuka Shinya, Toyokuni Shinya

CANCER SCIENCE Vol. 109 page： 830-830 2018.12

Polymer coating on carbon nanotubes into Durobeads is a novel strategy for human environmental safety.

Fumiya Ito, Hideyuki Hisashi, Shinya Toyokuni

Nagoya journal of medical science Vol. 80 ( 4 ) page： 597 - 604 2018.11

Language：English Publishing type：Research paper (scientific journal) Publisher：NAGOYA UNIV, SCH MED

Carbon nanotubes (CNTs) have attracted much business interest in industrial applications due to their high electrical and heat conductivities while being both durable and versatile. However. multiwall CNTs (MWCNTs) of similar to 50 nm diameter (NT50) have been shown to cause mesothelioma in rodents after direct exposure to mesothelial cells, and thus were classified as a Group 213 carcinogen to humans, which requires considerable regulations for use. In contrast, tangled MWCNTs of similar to 15 nm diameter (NTtngl) are not carcinogenic to rats, indicating that the physical dimension linked with mesothelial cellular uptake is an important factor for human environmental risk. In the present study, hypothesizing that dustability is another distinct risk factor, for the first time, we evaluated the toxicity of CNT granules (Durobeads) that were generated with a polymer coating to mesothelial cells. Polymer coating induced prominent agglomeration and significantly suppressed the dustability of CNTs in a dose-dependent manner, with a 10% polymer coating resulting in 730 times less dustability. These CNT granules revealed significantly lower mesothelial uptake and cytotoxicity in comparison to NT50 in in vitro assays. Similarly, in in vivo analyses, CNT granules induced limited peritoneal inflammation 4 weeks after intraperitoneal injection, whereas NT50 caused severe fibrosing inflammation. Previously, we demonstrated that the severity of inflammation by intraperitoneal injection in the subacute studies are in agreement with the mesothelial carcinogenicity by CNTs. Therefore, we suggest that adding a polymer coating to CNTs provides another smart strategy for the safe use of CNTs.

DOI： 10.18999/nagjms.80.4.597

Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice.

Funahashi S, Okazaki Y, Nishiyama T, Ohyoshi H, Yasui H, Nishida K, Matsui S, Toyokuni S

Free radical research page： 1-10 2018.10

Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial carcinogenesis: Toward the era of mesothelioma prevention.

Toyokuni S

Free radical biology & medicine 2018.10

Molecular mechanisms of non-thermal plasma-induced effects in cancer cells.

Tanaka H, Mizuno M, Ishikawa K, Toyokuni S, Kajiyama H, Kikkawa F, Hori M

Biological chemistry 2018.10

A special issue of SFRR Asia: Cross talk between free radicals and mitochondria in health and disease.

Liu J, Toyokuni S, Surh YJ

Free radical research page： 1-51 2018.9

Plasma Biology for a Novel Cancer Treatment

Toyokuni Shinya

JSAP Annual Meetings Extended Abstracts Vol. 2018.2 ( 0 ) page： 37 - 37 2018.9

動物モデルを用いたがん研究扁平上皮癌発症におけるHippo経路の役割(Animal models in cancer research Critical role of Hippo signaling pathway at the onset of squamous cell carcinomas)

鈴木聡, 西尾美希, 大森裕文, 藤庸子, 前濱朝彦, 青野ゆかり, 清野透, 田口健一, 益田宗幸, 豊國伸哉, 田代浩徳, 片渕秀隆

日本癌学会総会記事 Vol. 77回 page： 1110 - 1110 2018.9

アスベストが卵巣癌を起こす可能性についてクロシドライトは卵巣表層上皮におけるDNAの二本鎖切断を惹起する(Asbestos exposure as a possible cause of ovarian carcinogenesis)

本岡大社, 伊藤文哉, 田代浩徳, 片渕秀隆, 豊國伸哉

日本癌学会総会記事 Vol. 77回 page： 118 - 118 2018.9

Development of a novel monoclonal antibody against 4-hydroxy-2E,6Z-dodecadienal (4-HDDE)-protein adducts: Immunochemical application in quantitative and qualitative analyses of lipid peroxidation in vitro and ex vivo. International journal

Koji Uchida, Takahiro Shibata, Shinya Toyokuni, Bareket Daniel, Kamelija Zarkovic, Neven Zarkovic, Shlomo Sasson

Free radical biology & medicine Vol. 124 page： 12 - 20 2018.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Inc.

Non-enzymatic peroxidation of polyunsaturated fatty acids (PUFA) results in the formation of various α,β-unsaturated aldehydes, of which 4-hydroxyalkenals are abundant. The propensity of n-6 PUFA, such as linoleic acid, γ-linolenic acid and arachidonic acid, to undergo radical-induced peroxidation and generate 4-hydroxy-2E-nonenal (4-HNE) has been widely demonstrated. The ability of the latter to form covalent adducts with macromolecules and modify cellular functions has been linked to numerous pathological processes. Concomitantly, evidence has accumulated on specific signaling properties of low concentrations of 4-HNE that may induce hormetic and protective responses to peroxidation stress in cells. It has long been known that peroxidation of PUFA, and particularly arachidonic acid, also give rise to 4-hydroxy-2E,6Z-dodecadienal (4-HDDE), which is more chemically reactive than 4-HNE. Few studies on 4-HDDE revealed its ability to avidly interact covalently with electronegative moieties in macromolecules and to its ability to selectively activate the transcriptional regulator Peroxisome Proliferator-Activated Receptor (PPAR)-β/δ. The research on 4-HDDE has been impeded due to the lack of available pure 4-HDDE and antibodies that recognize 4-HDDE-modified epitopes in proteins. The purpose of this study was to employ an established procedure to synthesize 4-HDDE and use it to create and characterize a monoclonal antibody against 4-HDDE-modified proteins and establish its application for ELISA and immunohistochemical analysis of cells and tissues and further expand lipid peroxidation research.

DOI： 10.1016/j.freeradbiomed.2018.05.079

Non-thermal plasma as a simple ferroptosis inducer in cancer cells: A possible role of ferritin International journal

Furuta Takahiro, Shi Lei, Toyokuni Shinya

PATHOLOGY INTERNATIONAL Vol. 68 ( 7 ) page： 442 - 443 2018.7

Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model International journal

Kenji Imai, Tomomi Kotani, Hiroyuki Tsuda, Tomoko Nakano, Takafumi Ushida, Akira Iwase, Taku Nagai, Shinya Toyokuni, Akio Suzumura, Fumitaka Kikkawa

Scientific Reports Vol. 8 ( 1 ) page： 9221 2018.6

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

The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H2) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H2 attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Short-term memory, sociability and social novelty, and sensorimotor gating were evaluated using the Y-maze, three-chamber, and prepulse inhibition (PPI) tests, respectively, at postnatal 3 or 4 weeks. The number of neurons and oligodendrocytes was also analyzed at postnatal 5 weeks by immunohistochemical analysis. Offspring of the LPS-exposed dams showed deficits in short-term memory and social interaction, following neuronal and oligodendrocytic loss in the amygdala and cortex. Maternal H2 administration markedly attenuated these LPS-induced abnormalities. Moreover, we evaluated the effect of H2 on LPS-induced astrocytic activation, both in vivo and in vitro. The number of activated astrocytes with hypertrophic morphology was increased in LPS-exposed offspring, but decreased in the offspring of H2-administered dams. In primary cultured astrocytes, LPS-induced pro-inflammatory cytokines were attenuated by H2 administration. Overall, these findings indicate that maternal H2 administration exerts neuroprotective effects and ameliorates MIA-induced neurodevelopmental deficits of offspring later in life.

DOI： 10.1038/s41598-018-27626-4

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Papers - TOYOKUNI Shinya