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PathologyPathology and Biological Responses


Our laboratory (Toyokuni Laboratory) studies biological significance of oxidative stress from cell to human levels widely and deeply. We work on several different projects described below, by the use of genetic, biochemical as well as molecular approaches, still emphasizing on pathologic techniques. We seek for graduate students highly interested in oxidative stress, irrespective of their schools for bachelor. In our laboratory students can naturally learn basic animal/human histology/pathology, which are essential for analyzing genetically engineered animals. Japanese MD students can be in a training program for registered pathologists during the PhD course, and are given a part-time job in our affiliated hospitals. Shinya Toyokuni is the current President of the Society for Free Radical Japan (SFRR Japan) and of the Japanese Bioiron Society (JBIS). He is also the current President of SFRR Asia and SFRR International.

Research Projects

  1. Analysis of oxidative stress-induced carcinogenesis
    We have studied ferric nitrilotriacetate (Fe-NTA)-induced renal carcinogenesis model for more than 25 years, and are now in a maturation stage. We have been interested in a question whether there are any target genes for oxidative stress-induced carcinogenesis. In 2002, we published a paper in Am J Pathol with a commentary, describing that allelic loss of p16 tumor suppressor gene (a target gene) occurs as early as a few weeks after the start of Fe-NTA administration. Then, we proposed a concept of oxygenomics (Toyokuni and Akatsuka, J Clin Biochem Nutr 2006), which analyzes susceptible portions of the genome against oxidative stress. Thereafter, we have performed array-based comparative genomic hybridization analyses on Fe-NTA-induced renal cell carcinoma, which revealed massive chromosomal alterations, including amplifications and deletions in WILD-TYPE rats. These changes are not usually observed in other animal models but are quite similar to those of human cancers. Thus, we believe that fundamental cause of human cancer is oxidative stress via catalytic iron. We also work on preventive interventions, using this model.


  2. Toxicity and carcinogenicity studies on fibrous inorganic nanomaterials
    project2.jpgWe have been working on elucidating asbestos-induced mesothelial carcinogenesis since 2006 after Kubota shock. In the textbook, it is described that asbestos which contains high amounts of iron (crocidolite and amosite; blue and brown asbestos) is more than 100 times carcinogenic than asbestos that does not contain iron (chrysotile; white asbestos). However, this was not the case, especially with intraperitoneal administration. In 2012 we reported that white asbestos is as carcinogenic as blue and brown asbestos, when directly exposed to mesothelial cells (Jiang et al. 2012). This is closely associated with hemolysis by white asbestos, followed by adsorption of hemoglobin on its surface. Then, we showed that iron chelation therapy is useful for mesothelioma prevention in an animal model (Nagai et al. Cancer Prev Res 2013). We are currently developing novel therapeutic strategies as well. On the other hand, we evaluated novel fibrous nanomaterials (multiwalled carbon nanotubes; MWCNT), which are similar to asbestos in physical dimension. We found that its diameter is a critical factor for mesothelial carcinogenesis; namely MWCNT of 50 nm diameter was most carcinogenic (Nagai et al, PNAS 2011). This data was used for describing the carcinogenicity of 50 nm-MWCNT to be Group 2B by IARC. We believe that currently MWCNT is used with ample care in the society. We are working on its carcinogenic mechanisms.

  3. Development of oxidative stress markers and visualizing techniques
    project3.jpgBased on the several animal models mentioned above, we develop novel oxidative stress markers. Monitoring oxidative stress is very important because it is associated with a variety of pathologies, including atherosclerosis, diabetes and aging. Recently, we published a novel method to visualize catalytic ferrous iron with RhoNox-1 (Mukaide et al. Free Radic Res, 2014) with cooperative efforts. Fe(II) is important in initiating Fenton reaction in vivo.

  4. Studies on non-thermal (low temperature) plasma
    project4.jpgPlasma is the 4th condition of physical states, other than solid, liquid and gas, and consists of light, gas, electrons, radicals, ions, etc. Sun and thunder are the natural plasma, but they are in a high temperature. In the 1990’s, it has become possible to general plasma of near body temperature. We are currently trying to find out medical applications, using this non-thermal plasma. After a few years’ of experiments, we know that non-thermal plasma can load adjustable oxidative stress to any place we want (Okazaki et al. J Clin Biochem Nutr 2014). Thus, we hope to apply non-thermal plasma to sterilization, hemostasis and cancer therapy.

  5. Studies on pathologic diagnosis
    We work on several issues on the diagnostic problems of human specimens.

Faculty Members

TOYOKUNI, Shinya Professor Pathology and Biological Responses
OKAZAKI, Yasumasa Associate professor Pathology and Biological Responses
AKATSUKA, Shinya Lecturer Pathology and Biological Responses
MOTOOKA, Yashiro Assistant Professor Pathology and Biological Responses


  • 2024
    1. Mi D, Yanatori I, Zheng H, Kong Y, Hirayama T, Toyokuni S. Association of poly(rC)-binding protein-2 with sideroflexin-3 through TOM20 as an iron entry pathway to mitochondria. Free Radic Res. 2024 Apr 10:1-40. doi: 10.1080/10715762.2024.2340711. Epub ahead of print.
    2. Chen X, Tsvetkov AS, Shen HM, Isidoro C, Ktistakis NT, Linkermann A, Koopman WJH, Simon HU, Galluzzi L, Luo S, Xu D, Gu W, Peulen O, Cai Q, Rubinsztein DC, Chi JT, Zhang DD, Li C, Toyokuni S, Liu J, Roh JL, Dai E, Juhasz G, Liu W, Zhang J, Yang M, Liu J, Zhu LQ, Zou W, Piacentini M, Ding WX, Yue Z, Xie Y, Petersen M, Gewirtz DA, Mandell MA, Chu CT, Sinha D, Eftekharpour E, Zhivotovsky B, Besteiro S, Gabrilovich DI, Kim DH, Kagan VE, Bayir H, Chen GC, Ayton S, Lünemann JD, Komatsu M, Krautwald S, Loos B, Baehrecke EH, Wang J, Lane JD, Sadoshima J, Yang WS, Gao M, Münz C, Thumm M, Kampmann M, Yu D, Lipinski MM, Jones JW, Jiang X, Zeh HJ, Kang R, Klionsky DJ, Kroemer G, Tang D. International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis. Autophagy. 2024 Mar 24:1-34. doi: 10.1080/15548627.2024.2319901. Epub ahead of print.
    3. Dai E, Chen X, Linkermann A, Jiang X, Kang R, Kagan VE, Bayir H, Yang WS, Garcia-Saez AJ, Ioannou MS, Janowitz T, Ran Q, Gu W, Gan B, Krysko DV, Zhu X, Wang J, Krautwald S, Toyokuni S, Xie Y, Greten FR, Yi Q, Schick J, Liu J, Gabrilovich DI, Liu J, Zeh HJ, Zhang DD, Yang M, Iovanna J, Kopf M, Adolph TE, Chi JT, Li C, Ichijo H, Karin M, Sankaran VG, Zou W, Galluzzi L, Bush AI, Li B, Melino G, Baehrecke EH, Lotze MT, Klionsky DJ, Stockwell BR, Kroemer G, Tang D. A guideline on the molecular ecosystem regulating ferroptosis. Nat Cell Biol. 2024 Feb 29. doi: 10.1038/s41556-024-01360-8. Epub ahead of print.
    4. Tanaka H, Motooka Y, Maeda Y, Sonehara R, Nakamura T, Kajiyama H, Mashimo T, Toyokuni S. Brca2(p.T1942fs/+) dissipates ovarian reserve in rats through oxidative stress in follicular granulosa cells. Free Radic Res. 2024 Feb;58(2):130-143. doi: 10.1080/10715762.2024.2320405.
    5. Ito F, Yanatori I, Kato K, Toyokuni S. Protocol for the isolation of GFP-expressing ferroptosis-dependent extracellular vesicles in in vitro cell culture models. STAR Protoc. 2024 Mar 15;5(1):102892. doi: 10.1016/j.xpro.2024.102892.
    6. Jiang L, Zheng H, Ishida M, Lyu Q, Akatsuka S, Motooka Y, Sato K, Sekido Y, Nakamura K, Tanaka H, Ishikawa K, Kajiyama H, Mizuno M, Hori M, Toyokuni S. Elaborate cooperation of poly(rC)-binding proteins 1/2 and glutathione in ferroptosis induced by plasma-activated Ringer's lactate. Free Radic Biol Med. 2024 Mar;214:28-41. doi: 10.1016/j.freeradbiomed.2024.02.001.
    7. Sagou K, Sato Y, Okuno Y, Watanabe T, Inagaki T, Motooka Y, Toyokuni S, Murata T, Kiyoi H, Kimura H. Epstein-Barr virus lytic gene BNRF1 promotes B-cell lymphomagenesis via IFI27 upregulation. PLoS Pathog. 2024 Feb 1;20(2):e1011954. doi: 10.1371/journal.ppat.1011954.
  • 2023
    1. Sato K, Yang M, Nakamura K, Tanaka H, Hori M, Nishio M, Suzuki A, Hibi H, Toyokuni S. Ferroptosis induced by plasma-activated Ringer's lactate solution prevents oral cancer progression. Oral Dis. 2023 Dec 4. doi: 10.1111/odi.14827. Online ahead of print.
    2. Hiratsuka T, Yoshizawa A, Endo T, Yamamoto T, Toyokuni S, Tsuruyama T. FFPE Proteomics of Malignant Mesothelioma and New Candidate Biomarkers Thioredoxin and Superoxide Dismutase 2 for Immunohistochemistry. Lab Invest. 2023 Nov 25:100299. doi: 10.1016/j.labinv.2023.100299. Online ahead of print.
    3. Yamada K, Tazaki A, Ushio-Watanabe N, Usui Y, Takeda A, Matsunaga M, Suzumura A, Shimizu H, Zheng H, Ariefta NR, Yamamoto M, Hara H, Goto H, Sonoda KH, Nishiguchi KM, Kato M, Nishikawa Y, Toyokuni S, Kaneko H. Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis. Redox Biol. 2023 Nov;67:102890. doi: 10.1016/j.redox.2023.102890. Epub 2023 Sep 17.
    4. Yanatori I, Kishi F, Toyokuni S. New iron export pathways acting via holo-ferritin secretion. Arch Biochem Biophys. 2023 Sep 15;746:109737. doi: 10.1016/
    5. Toyokuni S, Kong Y, Katabuchi M, Maeda Y, Motooka Y, Ito F, Yanatori I. Iron links endogenous and exogenous nanoparticles. Arch Biochem Biophys. 2023 Sep 1;745:109718. doi: 10.1016/
    6. Van San E, Debruyne AC, Veeckmans G, Tyurina YY, Tyurin VA, Zheng H, Choi SM, Augustyns K, van Loo G, Michalke B, Venkataramani V, Toyokuni S, Bayir H, Vandenabeele P, Hassannia B, Vanden Berghe T. Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression. Cell Death Differ. 2023 Sep;30(9):2092-2103. doi:10.1038/s41418-023-01195-0.
    7. Ishikawa K, Takeda K, Yoshimura S, Kondo T, Tanaka H, Toyokuni S, Nakamura K, Kajiyama H, Mizuno M, Hori M. Generation and measurement of low-temperature plasma for cancer therapy: a historical review. Free Radic Res. 2023 Dec;57(3):239-270. doi: 10.1080/10715762.2023.2230351.
    8. Ito F, Kato K, Yanatori I, Maeda Y, Murohara T, Toyokuni S. Matrigel-based organoid culture of malignant mesothelioma reproduces cisplatin sensitivity through CTR1. BMC Cancer. 2023 May 31;23(1):487. doi:10.1186/s12885-023-10966-4.
    9. Miron C, Ishikawa K, Kashiwagura S, Suda Y, Tanaka H, Nakamura K, Kajiyama H, Toyokuni S, Mizuno M, Hori M. Cancer-specific cytotoxicity of Ringer's acetate solution irradiated by cold atmospheric pressure plasma. Free Radic Res. 2023 Apr 17:1-14. doi: 10.1080/10715762.2023.2201390. Epub ahead of print.
    10. Tsuji S, Brace CS, Yao R, Tanie Y, Tada H, Rensing N, Mizuno S, Almunia J, Kong Y, Nakamura K, Furukawa T, Ogiso N, Toyokuni S, Takahashi S, Wong M, Imai SI, Satoh A. Sleep-wake patterns are altered with age, Prdm13 signaling in the DMH, and diet restriction in mice. Life Sci Alliance. 2023 Apr 12;6(6):e202301992. doi: 10.26508/lsa.202301992.
    11. Yamaguchi SI, Xie Q, Ito F, Terao K, Kato Y, Kuroiwa M, Omori S, Taniura H, Kinoshita K, Takahashi T, Toyokuni S, Kasahara K, Nakayama M. Carbon nanotube recognition by human Siglec-14 provokes inflammation. Nat Nanotechnol. 2023 Apr 6. doi: 10.1038/s41565-023-01363-w. Epub ahead of print.
    12. Toyokuni S. Commentary on \"Mechanisms of asbestos-induced carcinogenesis\" published in 2009. Nagoya J Med Sci. 2023 Feb;85(1):13-15. doi:10.18999/nagjms.85.1.13.
    13. Toyokuni S. Toward the next century of the Nagoya Journal of Medical Science: message from the Editor-in-chief. Nagoya J Med Sci. 2023 Feb;85(1):1-4. doi:10.18999/nagjms.85.1.1.
    14. Sato K, Fujii K, Tanaka H, Hori M, Hibi H, Toyokuni S. Exposure of low-temperature plasma after vaccination in tongue promotes systemic IgM induction against spike protein of SARS-CoV-2. Free Radic Res. 2023 Jan;57(1):30-37. doi:10.1080/10715762.2023.2190486.
    15. Toyokuni S, Zheng H, Kong Y, Sato K, Nakamura K, Tanaka H, Okazaki Y. Low-temperature plasma as magic wand to differentiate between the good and the evil. Free Radic Res. 2023 Jan;57(1):38-46. doi: 10.1080/10715762.2023.2190860.
    16. Tanaka H, Mizuno M, Ishikawa K, Miron C, Okazaki Y, Toyokuni S, Nakamura K, Kajiyama H, Hori M. Plasma activated Ringer's lactate solution. Free Radic Res. 2023 Feb 23:1-13. doi: 10.1080/10715762.2023.2182663. Epub ahead of print.
    17. Canton-Vitoria R, Sato K, Motooka Y, Toyokuni S, Liu Z, Kitaura R. Field-effect transistor antigen/antibody-TMDs sensors for the detection of COVID-19 samples. Nanoscale. 2023 Feb 10. doi: 10.1039/d2nr06630k. Epub ahead of print.
    18. Toyokuni S, Kong Y, Motooka Y, Akatsuka S. Environmental impact on carcinogenesis under BRCA1 haploinsufficiency. Genes Environ. 2023 Jan 13;45(1):2. doi: 10.1186/s41021-023-00258-5
  • 2022
    1. Luo Y, Akatsuka S, Motooka Y, Kong Y, Zheng H, Mashimo T, Imaoka T, Toyokuni S. BRCA1 haploinsufficiency impairs iron metabolism to promote chrysotile-induced mesothelioma via ferroptosis-resistance. Cancer Sci. 2022 Dec 21. doi:10.1111/cas.15705. Epub ahead of print.
    2. Okazaki Y, Ito N, Tanaka H, Hori M, Toyokuni S. Non-thermal plasma elicits ferrous chloride-catalyzed DMPO-OH. Free Radic Res. 2022 Dec 15:1-12. doi:10.1080/10715762.2022.2157272. Epub ahead of print.
    3. Toyokuni S, Kong Y, Zheng H, Maeda Y, Katabuchi M, Motooka Y. Three-dimensional regulation of ferroptosis at the intersection of iron, sulfur and oxygen executing scrap and build toward evolution. Antioxid Redox Signal. 2022 Nov 18. doi:10.1089/ars.2022.0142. Epub ahead of print.
    4. Ohmori I, Ouchida M, Imai H, Ishida S, Toyokuni S, Mashimo T. Thioredoxin deficiency increases oxidative stress and causes bilateral symmetrical degeneration in rat midbrain. Neurobiol Dis. 2022 Nov;175:105921. doi:10.1016/j.nbd.2022.105921. Epub ahead of print.
    5. Hiratsuka T, Yamamoto T, Yoshizawa A, Toyokuni S, Tsuruyama T. RhoA and vigilin are candidates for immunohistochemical markers for epithelioid malignant mesothelioma. Sci Rep. 2022 Nov;12(1):18519. doi:10.1038/s41598-022-20334-0.
    6. Motooka Y, Toyokuni S. Ferroptosis as ultimate target of cancer therapy. Antioxid Redox Signal. 2022 Aug 9. doi:.1089/ars.2022.0048. Epub ahead of print.
    7. Aoki C, Imai K, Mizutani T, Sugiyama D, Miki R, Koya Y, Kobayashi T, Ushida T, Iitani Y, Nakamura N, Owaki T, Nishikawa H, Toyokuni S, Kajiyama H, Kotani T. Molecular hydrogen has a positive impact on pregnancy maintenance through enhancement of mitochondrial function and immunomodulatory effects on T cells. Life Sci. 2022 Nov 1;308:120955. doi: 10.1016/j.lfs.2022.120955.
    8. Sato K, Fujii K, Yamamoto N, Ichimura N, Yamaguchi S, Yamada H, Hibi H, Toyokuni S. Association of alcohol intake and female gender with high expression of TMPRSS2 in tongue as potential risk for SARS-CoV-2 infection. J Clin Biochem Nutr. 2022 Sep;71(2):129-135. doi: 10.3164/jcbn.21-172.
    9. Toyokuni S, Kong Y, Zheng H, Maeda Y, Motooka Y, Akatsuka S. Iron as spirit of life to share under monopoly. J Clin Biochem Nutr. 2022 Sep;71(2):78-88. doi:10.3164/jcbn.22-43.
    10. Lyu Q, Jiang L, Zheng H, Hayashi S, Sato K, Toyokuni S. Diluted aqueous extract of heat-not-burn tobacco product smoke causes less oxidative damage in fibroblasts than conventional cigarette. J Clin Biochem Nutr. 2022 Jul;71(1):55-63. doi: 10.3164/jcbn.21-134.
    11. Soyama H, Nishio M, Otani J, Sakuma T, Takao S, Hara S, Masuda T, Mimori K, Toyokuni S, Lydon JP, Nakao K, Nishina H, Fukumoto T, Maehama T, Suzuki A. Hippo-TAZ signaling is the master regulator of the onset of triple-negative basal-like breast cancers. Proc Natl Acad Sci U S A. 2022 Jul 19;119(29):e2123134119. doi: 10.1073/pnas.2123134119.
    12. Igarashi N, Miyata K, Loo TM, Chiba M, Hanyu A, Nishio M, Kawasaki H, Zheng H, Toyokuni S, Kon S, Moriyama K, Fujita Y, Takahashi A. Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells. Nat Commun. 2022 Jul 18;13(1):4157. doi: 10.1038/s41467-022-31642-4.
    13. Murphy MP, Bayir H, Belousov V, Chang CJ, Davies KJA, Davies MJ, Dick TP, Finkel T, Forman HJ, Janssen-Heininger Y, Gems D, Kagan VE, Kalyanaraman B, Larsson NG, Milne GL, Nyström T, Poulsen HE, Radi R, Van Remmen H, Schumacker PT, Thornalley PJ, Toyokuni S, Winterbourn CC, Yin H, Halliwell B. Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo. Nat Metab. 2022 Jun;4(6):651-662. doi: 10.1038/s42255-022-00591-z.
    14. Kong Y, Akatsuka S, Motooka Y, Zheng H, Cheng Z, Shiraki Y, Mashimo T, Imaoka T, Toyokuni S. BRCA1 haploinsufficiency promotes chromosomal amplification under Fenton reaction-based carcinogenesis through ferroptosis-resistance. Redox Biol. 2022 May 28;54:102356. doi:10.1016/j.redox.2022.102356.
    15. Toyokuni S, Noguchi N, Niki E. Editorial: Centennial anniversary of vitamin E discovery. Free Radic Biol Med. 2022 Apr;183:125-126. doi:10.1016/j.freeradbiomed.2022.03.018.
    16. Yue L, Luo Y, Jiang L, Sekido Y, Toyokuni S. PCBP2 knockdown promotes ferroptosis in malignant mesothelioma. Pathol Int. 2022 Apr;72(4):242-251. doi:10.1111/pin.13209.
    17. Okazaki Y, Sasaki K, Ito N, Tanaka H, Matsumoto KI, Hori M, Toyokuni S. Tetrachloroaurate (III)-induced oxidation increases non-thermal plasma-induced oxidative stress. Free Radic Res. 2022 Jan 25:1-11. doi:10.1080/10715762.2022.2026348.
    18. Toyokuni S, Kong Y, Mi D. Commentary for an article on photooxidation in isolated chloroplasts. Arch Biochem Biophys. 2022 Jan 22:109133. doi:10.1016/
    19. Sato Y, Oguchi A, Fukushima Y, Masuda K, Toriu N, Taniguchi K, Yoshikawa T, Cui X, Kondo M, Hosoi T, Komidori S, Shimizu Y, Fujita H, Jiang L, Kong Y, Yamanashi T, Seita J, Yamamoto T, Toyokuni S, Hamazaki Y, Hattori M, Yoshikai Y, Boor P, Floege J, Kawamoto H, Murakawa Y, Minato N, Yanagita M. CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury. J Clin Invest. 2022 Jan 18;132(2):e146071. doi:10.1172/JCI146071.
  • 2021
    1. Toyokuni S, Kong Y, Zheng H, Mi D, Katabuchi M, Motooka Y, Ito F. Double-edged Sword Role of Iron-loaded Ferritin in Extracellular Vesicles. J Cancer Prev. 2021 Dec 30;26(4):244-249. doi: 10.15430/JCP.2021.26.4.244.
    2. Okazaki Y. Asbestos-induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species. Pathol Int. 2021 Dec 29. doi:10.1111/pin.13196. Epub ahead of print.
    3. Zheng H, Jiang L, Tsuduki T, Conrad M, Toyokuni S. Embryonal erythropoiesis and aging exploit ferroptosis. Redox Biol. 2021 Oct 30;48:102175. doi:10.1016/j.redox.2021.102175.
    4. Ito F, Kato K, Yanatori I, Murohara T, Toyokuni S. Ferroptosis-dependent extracellular vesicles from macrophage contribute to asbestos-induced mesothelial carcinogenesis through loading ferritin. Redox Biol. 2021 Oct 21;47:102174. doi: 10.1016/j.redox.2021.102174.
    5. Cheng Z, Akatsuka S, Li GH, Mori K, Takahashi T, Toyokuni S. Ferroptosis-resistance determines high susceptibility of murine A/J strain to iron-induced renal carcinogenesis. Cancer Sci. 2022 Jan;113(1):65-78. doi: 10.1111/cas.15175.
    6. Yogosawa S, Ohkido M, Horii T, Okazaki Y, Nakayama J, Yoshida S, Toyokuni S, Hatada I, Morimoto M, Yoshida K. Mice lacking DYRK2 exhibit congenital malformations with lung hypoplasia and altered Foxf1 expression gradient. Commun Biol. 2021 Oct 20;4(1):1204. doi: 10.1038/s42003-021-02734-6.
    7. Checker R, Sharma D, Sandur SK, Toyokuni S. Role and management of oxidative stress in human disease. Free Radic Res. 2021 Aug;55(8):755-757. doi: 10.1080/10715762.2021.1991083.
    8. Valacchi G, Pecorelli A, Toyokuni S. Mitochondrial involvement in the development and progression of diseases. Arch Biochem Biophys. 2021 Oct 30;711:109006. doi: 10.1016/
    9. Miyata K, Imai Y, Hori S, Nishio M, Loo TM, Okada R, Yang L, Nakadai T, Maruyama R, Fujii R, Ueda K, Jiang L, Zheng H, Toyokuni S, Sakata T, Shirahige K, Kojima R, Nakayama M, Oshima M, Nagayama S, Seimiya H, Hirota T, Saya H, Hara E, Takahashi A. Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer. Proc Natl Acad Sci U S A. 2021 Aug 31;118:e2025647118. doi: 10.1073/pnas.2025647118.
    10. Miura M, Imai K, Tsuda H, Miki R, Tano S, Ito Y, Hirako-Takamura S, Moriyama Y, Ushida T, Iitani Y, Nakano-Kobayashi T, Toyokuni S, Kajiyama H, Kotani T. Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia. Int J Mol Sci. 2021 Aug 31;22:9500. doi: 10.3390/ijms22179500.
    11. Tanaka H, Hosoi Y, Ishikawa K, Yoshitake J, Shibata T, Uchida K, Hashizume H, Mizuno M, Okazaki Y, Toyokuni S, Nakamura K, Kajiyama H, Kikkawa F, Hori M. Low temperature plasma irradiation products of sodium lactate solution that induce cell death on U251SP glioblastoma cells were identified. Sci Rep. 2021 Sep 16;11:18488. doi: 10.1038/s4
    12. Yanatori I, Richardson DR, Dhekne HS, Toyokuni S, Kishi F. CD63 is Regulated by Iron via the IRE-IRP System and is Important for Ferritin Secretion by Extracellular Vesicles. Blood. 2021 Jul 15:blood.2021010995. doi: 10.1182/blood.2021010995.
    13. Tanaka H, Mizuno M, Ishikawa K, Toyokuni S, Kajiyama H, Kikkawa F, Hori M. Cancer treatments using low-temperature plasma. Curr Med Chem. 2021 Jun 29. doi: 10.2174/0929867328666210629121731.
    14. Okazaki Y, Tanaka H, Matsumoto KI, Hori M, Toyokuni S. Non-thermal plasma-induced DMPO-OH yields hydrogen peroxide. Arch Biochem Biophys. 2021 Jul 15;705:108901. doi: 10.1016/
    15. Nakamura K, Yoshikawa N, Mizuno Y, Ito M, Tanaka H, Mizuno M, Toyokuni S, Hori M, Kikkawa F, Kajiyama H. Preclinical Verification of the Efficacy and Safety of Aqueous Plasma for Ovarian Cancer Therapy. Cancers (Basel). 2021 Mar 7;13(5):1141. doi: 10.3390/cancers13051141.
    16. Jiang L, Zheng H, Lyu Q, Hayashi S, Sato K, Sekido Y, Nakamura K, Tanaka H, Ishikawa K, Kajiyama H, Mizuno M, Hori M, Toyokuni S. Lysosomal nitric oxide determines transition from autophagy to ferroptosis after exposure to plasma-activated Ringer's lactate. Redox Biol. 2021 Jul;43:101989. doi: 10.1016/j.redox.2021.101989.
    17. Klionsky DJ, Abdel-Aziz AK, Toyokuni S et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy. 2021 Jan;17(1):1-382. doi: 10.1080/15548627.2020.1797280.
    18. Omori S, Tsugita M, Hoshikawa Y, Morita M, Ito F, Yamaguchi SI, Xie Q, Noyori O, Yamaguchi T, Takada A, Saitoh T, Toyokuni S, Akiba H, Nagata S, Kinoshita K, Nakayama M. Tim4 recognizes carbon nanotubes and mediates phagocytosis leading to granuloma formation. Cell Rep. 2021 Feb 9;34(6):108734. doi: 10.1016/j.celrep.2021.108734.
    19. Okazaki Y, Ishidzu Y, Ito F, Tanaka H, Hori M, Toyokuni S. L-Dehydroascorbate efficiently degrades non-thermal plasma-induced hydrogen peroxide. Arch Biochem Biophys. 2021 Mar 30;700:108762. doi: 10.1016/
    20. Yamashita K, Kohashi K, Yamada Y, Akatsuka S, Ikuta K, Nishida Y, Toyokuni S, Oda Y. Prognostic significance of the MDM2/HMGA2 ratio and histological tumor grade in dedifferentiated liposarcoma. Genes Chromosomes Cancer. 2021 Jan;60(1):26-37. doi: 10.1002/gcc.22899.
    21. Homma T, Takeda Y, Nakano T, Akatsuka S, Kinoshita D, Kurahashi T, Saitoh S, Yamada KI, Miyata S, Asao H, Goto K, Watanabe T, Watanabe M, Toyokuni S, Fujii J. Defective biosynthesis of ascorbic acid in Sod1-deficient mice results in lethal damage to lung tissue. Free Radic Biol Med. 2021 Jan;162:255-265. doi: 10.1016/j.freeradbiomed.2020.10.023
  • 2020
    1. Koga Y, Tsuchimoto D, Hayashi Y, Abolhassani N, Yoneshima Y, Sakumi K, Nakanishi H, Toyokuni S, Nakabeppu Y. Neural stem cell-specific ITPA deficiency causes neural depolarization and epilepsy. JCI Insight. 2020 Nov 19;5(22):e140229. doi: 10.1172/jci.insight.140229.
    2. Oteiza PI, Toyokuni S. The new era for research on polyphenols and food factors. Arch Biochem Biophys. 2020 Dec 15;696:108678. doi: 10.1016/
    3. Toyokuni S, Kong Y, Cheng Z, Sato K, Hayashi S, Ito F, Jiang L, Yanatori I, Okazaki Y, Akatsuka S. Carcinogenesis as Side Effects of Iron and Oxygen Utilization: From the Unveiled Truth toward Ultimate Bioengineering. Cancers (Basel). 2020 Nov 10;12(11):3320. doi: 10.3390/cancers12113320.
    4. Hayashi S, Nakamura T, Motooka Y, Ito F, Jiang L, Akatsuka S, Iwase A, Kajiyama H, Kikkawa F, Toyokuni S. Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice. Redox Biol. 2020 Oct;37:101726. doi: 10.1016/j.redox.2020.101726.
    5. Ito F, Yanatori I, Maeda Y, Nimura K, Ito S, Hirayama T, Nagasawa H, Kohyama N, Okazaki Y, Akatsuka S, Toyokuni S. Asbestos conceives Fe(II)-dependent mutagenic stromal milieu through ceaseless macrophage ferroptosis and b-catenin induction in mesothelium. Redox Biol. 2020 Sep;36:101616. doi: 10.1016/j.redox.2020.101616.
    6. Nishio M, To Y, Maehama T, Aono Y, Otani J, Hikasa H, Kitagawa A, Mimori K, Sasaki T, Nishina H, Toyokuni S, Lydon JP, Nakao K, Wah Mak T, Kiyono T, Katabuchi H, Tashiro H, Suzuki A. Endogenous YAP1 activation drives immediate onset of cervical carcinoma in situ in mice. Cancer Sci. 2020 Oct;111(10):3576-3587. doi: 10.1111/cas.14581.
    7. Ohara Y, Enomoto A, Tsuyuki Y, Sato K, Iida T, Kobayashi H, Mizutani Y, Miyai Y, Hara A, Mii S, Suzuki J, Yamashita K, Ito F, Motooka Y, Misawa N, Fukui T, Kawaguchi K, Yokoi K, Toyokuni S. Connective tissue growth factor produced by cancer associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma. Oncol Rep. 2020 Sep;44(3):838-848. doi: 10.3892/or.2020.7669.
    8. Yanatori I, Richardson DR, Toyokuni S, Kishi F. The new role of poly (rC)-binding proteins as iron transport chaperones: Proteins that could couple with inter-organelle interactions to safely traffic iron. Biochim Biophys Acta Gen Subj. 2020 Nov;1864(11):129685. doi: 10.1016/j.bbagen.2020.129685.
    9. Li Z, Jiang L, Toyokuni S. Role of carbonic anhydrases in ferroptosis- resistance. Arch Biochem Biophys. 2020 Aug 15;689:108440. doi: 10.1016/
    10. Ishikawa K, Hosoi Y, Tanaka H, Jiang L, Toyokuni S, Nakamura K, Kajiyama H, Kikkawa F, Mizuno M, Hori M. Non-thermal plasma-activated lactate solution kills U251SP glioblastoma cells in an innate reductive manner with altered metabolism. Arch Biochem Biophys. 2020 Jul 30;688:108414. doi: 10.1016/
    11. Naito Y, Toyokuni S, Uchida K. The New Era for Redox Research. Free Radic Res. 2020 May 26:1-7. doi: 10.1080/10715762.2020.1774177.
    12. Toyokuni S, Yanatori I, Kong Y, Zheng H, Motooka Y, Jiang L. Ferroptosis at the crossroads of infection, aging and cancer. Cancer Sci. 2020 Aug;111(8):2665-2671. doi: 10.1111/cas.14496.
    13. Akatsuka S, Li GH, Kawaguchi S, Takahashi T, Yoshihara M, Suyama M, Toyokuni S. Augmented oxidative stress increases 8-oxoguanine preferentially in the transcriptionally active genomic regions. Free Radic Res. 2020 Apr 16:1-11. doi: 10.1080/10715762.2020.1733548.
    14. Okazaki Y, Chew SH, Nagai H, Yamashita Y, Ohara H, Jiang L, Akatsuka S, Takahashi T, Toyokuni S. Overexpression of miR-199/214 is a distinctive feature of iron-induced and asbestos-induced sarcomatoid mesothelioma in rats. Cancer Sci. 2020 Jun;111(6):2016-2027. doi: 10.1111/cas.14405.
    15. Funahashi S, Okazaki Y, Akatsuka S, Takahashi T, Sakumi K, Nakabeppu Y, Toyokuni S. Mth1 deficiency provides longer survival upon intraperitoneal crocidolite injection in female mice. Free Radic Res. 2020 Mar;54(2-3):195-205. doi: 10.1080/10715762.2020.1743285.
    16. Okazaki Y, Misawa N, Akatsuka S, Kohyama N, Sekido Y, Takahashi T, Toyokuni S. Frequent homozygous deletion of Cdkn2a/2b in tremolite-induced malignant mesothelioma in rats. Cancer Sci. 2020 Apr;111(4):1180-1192. doi: 10.1111/cas.14358.
    17. Yoshikawa N, Liu W, Nakamura K, Yoshida K, Ikeda Y, Tanaka H, Mizuno M, Toyokuni S, Hori M, Kikkawa F, Kajiyama H. Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway. Sci Rep. 2020 Jan 31;10(1):1614. doi: 10.1038/s41598-020-58667-3.
  • 2019
    1. Tanaka H, Mizuno M, Katsumata Y, Ishikawa K, Kondo H, Hashizume H, Okazaki Y, Toyokuni S, Nakamura K, Yoshikawa N, Kajiyama H, Kikkawa F, Hori M. Oxidative stress-dependent and -independent death of glioblastoma cells induced by non- thermal plasma-exposed solutions. Sci Rep. 2019 Sep 20;9(1):13657. doi: 10.1038/s41598-019-50136-w.
    2. Li Z, Jiang L, Chew SH, Hirayama T, Sekido Y, Toyokuni S. Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia. Redox Biol. 2019 Sep;26:101297. doi: 10.1016/j.redox.2019.101297.
    3. Yanatori I, Richardson DR, Toyokuni S, Kishi F. How iron is handled in the course of heme catabolism: Integration of heme oxygenase with intracellular iron transport mechanisms mediated by poly (rC)-binding protein-2. Arch Biochem Biophys. 2019 Sep 15;672:108071. doi: 10.1016/
    4. Sato K, Shi L, Ito F, Ohara Y, Motooka Y, Tanaka H, Mizuno M, Hori M, Hirayama T, Hibi H, Toyokuni S. Non-thermal plasma specifically kills oral squamous cell carcinoma cells in a catalytic Fe(II)-dependent manner. J Clin Biochem Nutr. 2019 Jul;65(1):8-15. doi: 10.3164/jcbn.18-91.
    5. Okazaki Y, Tanaka H, Hori M, Toyokuni S. l-Dehydroascorbic acid recycled by thiols efficiently scavenges non-thermal plasma-induced hydroxyl radicals. Arch Biochem Biophys. 2019 Jul 15;669:87-95. doi: 10.1016/
    6. Funahashi S, Okazaki Y, Nagai H, Chew SH, Ogawa K, Toyoda T, Cho YM, Toyokuni S. Twist1 was detected in mesenchymal cells of mammary fibroadenoma and invasive components of breast carcinoma in rats. J Toxicol Pathol. 2019 Jan;32(1):19-26. doi: 10.1293/tox.2018-0029.
    7. Harigae H, Hino K, Toyokuni S. Iron as Soul of Life on Earth Revisited: From Chemical Reaction, Ferroptosis to Therapeutics. Free Radic Biol Med. 2019 Mar;133:1-2. doi: 10.1016/j.freeradbiomed.2019.01.042.
    8. Kagawa T, Zarybnicky T, Omi T, Shirai Y, Toyokuni S, Oda S, Yokoi T. A scrutiny of circulating microRNA biomarkers for drug-induced tubular and glomerular injury in rats. Toxicology. 2019 Mar 1;415:26-36. doi: 10.1016/j.tox.2019.01.011.
    9. Kurake N, Ishikawa K, Tanaka H, Hashizume H, Nakamura K, Kajiyama H, Toyokuni S, Kikkawa F, Mizuno M, Hori M. Non-thermal plasma-activated medium modified metabolomic profiles in the glycolysis of U251SP glioblastoma. Arch Biochem Biophys. 2019 Feb 15;662:83-92. doi: 10.1016/
    10. Toyokuni S. Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial carcinogenesis: Toward the era of mesothelioma prevention. Free Radic Biol Med. 2019 Mar;133:206-215. doi: 10.1016/j.freeradbiomed.2018.10.401.
  • 2018
    1. Funahashi S, Okazaki Y, Nagai H, Chew SH, Ogawa K, Toyoda T, Cho YM, Toyokuni S. Twist1 was detected in mesenchymal cells of mammary fibroadenoma and invasive components of breast carcinoma in rats. J Toxicol Pathol. 2019 Jan;32(1):19-26. doi: 10.1293/tox.2018-0029.
    2. Ito F, Hisashi H, Toyokuni S. Polymer coating on carbon nanotubes into Durobeads is a novel strategy for human environmental safety. Nagoya J Med Sci. 2018 Nov;80(4):597-604. doi: 10.18999/nagjms.80.4.597.
    3. Kurake N, Ishikawa K, Tanaka H, Hashizume H, Nakamura K, Kajiyama H, Toyokuni S, Kikkawa F, Mizuno M, Hori M. Non-thermal plasma-activated medium modified metabolomic profiles in the glycolysis of U251SP glioblastoma. Arch Biochem Biophys. 2019 Feb 15;662:83-92. doi: 10.1016/
    4. Toyokuni S. Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial carcinogenesis: Toward the era of mesothelioma prevention. Free Radic Biol Med. 2019 Mar;133:206-215. doi: 10.1016/j.freeradbiomed.2018.10.401.
    5. Funahashi S, Okazaki Y, Nishiyama T, Ohyoshi H, Yasui H, Nishida K, Matsui S, Toyokuni S. Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice. Free Radic Res. 2018 Sep;52(9):1030-1039. doi: 10.1080/10715762.2018.1514604. Epub 2018 Oct 12. PMID: 30309285.
    6. Tanaka H, Mizuno M, Ishikawa K, Toyokuni S, Kajiyama H, Kikkawa F, Hori M. Molecular mechanisms of non-thermal plasma-induced effects in cancer cells. Biol Chem. 2018 Dec 19;400(1):87-91. doi: 10.1515/hsz-2018-0199.
    7. Liu J, Toyokuni S, Surh YJ. A special issue of SFRR Asia: cross talk between free radicals and mitochondria in health and disease. Free Radic Res. 2018 Dec;52(11-12):1197-1198. doi: 10.1080/10715762.2018.1528501.
    8. Imai K, Kotani T, Tsuda H, Nakano T, Ushida T, Iwase A, Nagai T, Toyokuni S, Suzumura A, Kikkawa F. Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model. Sci Rep. 2018 Jun 15;8(1):9221. doi: 10.1038/s41598-018-27626-4.
    9. Takeshita S, Yamashita Y, Shiomi K, Suzuki N, Yoshida J, Naiki-Ito A, Suzuki S, Akatsuka S, Toyokuni S, Takahashi T, Mase S, Arakawa A, Sugiura-Ogasawara M, Takahashi S. Expression of P-REX2a is associated with poor prognosis in endometrial malignancies. Oncotarget. 2018 May 15;9(37):24778-24786. doi: 10.18632/oncotarget.25349.
    10. Uchida K, Shibata T, Toyokuni S, Daniel B, Zarkovic K, Zarkovic N, Sasson S. 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. Free Radic Biol Med. 2018 Aug 20;124:12-20. doi: 10.1016/j.freeradbiomed.2018.05.079.
    11. Nakano T, Kotani T, Imai K, Iitani Y, Ushida T, Tsuda H, Li H, Iwase A, Toyokuni S, Kikkawa F. Effect of molecular hydrogen on uterine inflammation during preterm labour. Biomed Rep. 2018 May;8(5):454-460. doi: 10.3892/br.2018.1082.
    12. Ohara Y, Chew SH, Misawa N, Wang S, Somiya D, Nakamura K, Kajiyama H, Kikkawa F, Tsuyuki Y, Jiang L, Yamashita K, Sekido Y, Lipson KE, Toyokuni S. Connective tissue growth factor-specific monoclonal antibody inhibits growth of malignant mesothelioma in an orthotopic mouse model. Oncotarget. 2018 Apr 6;9(26):18494-18509. doi: 10.18632/oncotarget.24892.
    13. Akatsuka S, Li GH, Toyokuni S. Superiority of rat over murine model for studies on the evolution of cancer genome. Free Radic Res. 2018 Dec;52(11-12):1323-1327. doi: 10.1080/10715762.2018.1467562.
    14. Furuta T, Shi L, Toyokuni S. Non-thermal plasma as a simple ferroptosis inducer in cancer cells: A possible role of ferritin. Pathol Int. 2018 Jul;68(7):442-443. doi: 10.1111/pin.12665.
    15. Ohara Y, Kato S, Yamashita D, Satou A, Shimoyama Y, Hamaie C, Sato M, Ban N, Yamamoto K, Yamada T, Kawai H, Ohshima K, Nakamura S, Toyokuni S. An autopsy case report: Differences in radiological images correlate with histology in Erdheim-Chester disease. Pathol Int. 2018 Jun;68(6):374-381. doi: 10.1111/pin.12663.
    16. Ohara Y, Ito T, Ito M, Yamashita K, Toyokuni S. Acute fulminant invasive pulmonary aspergillosis in an immunocompetent host: An autopsy case report. Med Mycol Case Rep. 2018 Feb 9;20:39-42. doi: 10.1016/j.mmcr.2018.02.002.
    17. Ohara Y, Chew SH, Shibata T, Okazaki Y, Yamashita K, Toyokuni S. Phlebotomy as a preventive measure for crocidolite-induced mesothelioma in male rats. Cancer Sci. 2018 Feb;109(2):330-339. doi: 10.1111/cas.13460.
    18. Yamashita K, Kohashi K, Yamada Y, Ishii T, Nishida Y, Urakawa H, Ito I, Takahashi M, Inoue T, Ito M, Ohara Y, Oda Y, Toyokuni S. Osteogenic differentiation in dedifferentiated liposarcoma: a study of 36 cases in comparison to the cases without ossification. Histopathology. 2018 Apr;72(5):729-738. doi: 10.1111/his.13421.
  • 2017
    1. Hirako S, Tsuda H, Ito F, Okazaki Y, Hirayama T, Nagasawa H, Nakano T, Imai K, Kotani T, Kikkawa F, Toyokuni S. Role of catalytic iron and oxidative stress in nitrofen-induced congenital diaphragmatic hernia and its amelioration by Saireito (TJ-114). J Clin Biochem Nutr. 2017 Nov;61(3):176-182. doi: 10.3164/jcbn.17-17.
    2. Yamashita K, Kohashi K, Yamada Y, Ishii T, Nishida Y, Urakawa H, Ito I, Takahashi M, Inoue T, Ito M, Ohara Y, Oda Y, Toyokuni S. Osteogenic differentiation in dedifferentiated liposarcoma: a study of 36 cases in comparison to the cases without ossification. Histopathology. 2018 Apr;72(5):729-738. doi: 10.1111/his.13421.
    3. Li GH, Akatsuka S, Chew SH, Jiang L, Nishiyama T, Sakamoto A, Takahashi T, Futakuchi M, Suzuki H, Sakumi K, Nakabeppu Y, Toyokuni S. Fenton reaction- induced renal carcinogenesis in Mutyh-deficient mice exhibits less chromosomal aberrations than the rat model. Pathol Int. 2017 Nov;67(11):564-574. doi: 10.1111/pin.12598.
    4. Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascón S, Hatzios SK, Kagan VE, Noel K, Jiang X, Linkermann A, Murphy ME, Overholtzer M, Oyagi A, Pagnussat GC, Park J, Ran Q, Rosenfeld CS, Salnikow K, Tang D, Torti FM, Torti SV, Toyokuni S, Woerpel KA, Zhang DD. Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell. 2017 Oct 5;171(2):273-285. doi: 10.1016/j.cell.2017.09.021.
    5. Okazaki Y, Okada S, Toyokuni S. Astaxanthin ameliorates ferric nitrilotriacetate-induced renal oxidative injury in rats. J Clin Biochem Nutr. 2017 Jul;61(1):18-24. doi: 10.3164/jcbn.16-114.
    6. Nakamura K, Peng Y, Utsumi F, Tanaka H, Mizuno M, Toyokuni S, Hori M, Kikkawa F, Kajiyama H. Novel Intraperitoneal Treatment With Non-Thermal Plasma-Activated Medium Inhibits Metastatic Potential of Ovarian Cancer Cells. Sci Rep. 2017 Jul 20;7(1):6085. doi: 10.1038/s41598-017-05620-6.
    7. Yanatori I, Richardson DR, Toyokuni S, Kishi F. The iron chaperone poly(rC)-binding protein 2 forms a metabolon with the heme oxygenase 1/cytochrome P450 reductase complex for heme catabolism and iron transfer. J Biol Chem. 2017 Aug 11;292(32):13205-13229. doi: 10.1074/jbc.M117.776021.
    8. Toyokuni S, Jiang L. In response to Sharing different perspectives to understand asbestos-induced carcinogenesis: A comment to Jiang et al. (2016) by Alessandro Francesco Gualtieri (2017). Cancer Sci. 2017 May;108(5):1089-1090. doi: 10.1111/cas.13224.
    9. Yoshimaru T, Aihara K, Komatsu M, Matsushita Y, Okazaki Y, Toyokuni S, Honda J, Sasa M, Miyoshi Y, Otaka A, Katagiri T. Stapled BIG3 helical peptide ERAP potentiates anti-tumour activity for breast cancer therapeutics. Sci Rep. 2017 May 12;7(1):1821. doi: 10.1038/s41598-017-01951-6.
    10. Shi L, Ito F, Wang Y, Okazaki Y, Tanaka H, Mizuno M, Hori M, Hirayama T, Nagasawa H, Richardson DR, Toyokuni S. Non-thermal plasma induces a stress response in mesothelioma cells resulting in increased endocytosis, lysosome biogenesis and autophagy. Free Radic Biol Med. 2017 Jul;108:904-917. doi: 10.1016/j.freeradbiomed.2017.04.368.
    11. Han YP, Enomoto A, Shiraki Y, Wang SQ, Wang X, Toyokuni S, Asai N, Ushida K, Ara H, Ohka F, Wakabayashi T, Ma J, Natsume A, Takahashi M. Significance of low mTORC1 activity in defining the characteristics of brain tumor stem cells. Neuro Oncol. 2017 May 1;19(5):636-647. doi: 10.1093/neuonc/now237.
    12. Toyokuni S, Ito F, Yamashita K, Okazaki Y, Akatsuka S. Iron and thiol redox signaling in cancer: An exquisite balance to escape ferroptosis. Free Radic Biol Med. 2017 Jul;108:610-626. doi: 10.1016/j.freeradbiomed.2017.04.024.
    13. Yamashita K, Kohashi K, Yamada Y, Nishida Y, Urakawa H, Oda Y, Toyokuni S. Primary extraskeletal osteosarcoma: a clinicopathological study of 18 cases focusing on MDM2 amplification status. Hum Pathol. 2017 May;63:63-69. doi: 10.1016/j.humpath.2017.02.007.
    14. Chew SH, Okazaki Y, Akatsuka S, Wang S, Jiang L, Ohara Y, Ito F, Saya H, Sekido Y, Toyokuni S. Rheostatic CD44 isoform expression and its association with oxidative stress in human malignant mesothelioma. Free Radic Biol Med. 2017 May;106:91-99. doi: 10.1016/j.freeradbiomed.2017.02.011.
    15. Kajiyama H, Utsumi F, Nakamura K, Tanaka H, Toyokuni S, Hori M, Kikkawa F. Future perspective of strategic non-thermal plasma therapy for cancer treatment. J Clin Biochem Nutr. 2017 Jan;60(1):33-38. doi: 10.3164/jcbn.16-65.
    16. Shikata Y, Yoshimaru T, Komatsu M, Katoh H, Sato R, Kanagaki S, Okazaki Y, Toyokuni S, Tashiro E, Ishikawa S, Katagiri T, Imoto M. Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin- containing protein inhibitor. Cancer Sci. 2017 Apr;108(4):785-794. doi: 10.1111/cas.13175.
  • 2016
    1. Wang Y, Okazaki Y, Shi L, Kohda H, Tanaka M, Taki K, Nishioka T, Hirayama T, Nagasawa H, Yamashita Y, Toyokuni S. Role of hemoglobin and transferrin in multi-wall carbon nanotube-induced mesothelial injury and carcinogenesis. Cancer Sci. 2016; 107: 250-7.
    2. Wang S, Jiang L, Han Y, Hwu Chew S, Ohara Y, Akatsuka S, Weng L, Kawaguchi K, Fukui T, Sekido Y, Yokoi K, Toyokuni S. Urokinase-type plasminogen activator receptor promotes proliferation and invasion with reduced cisplatin sensitivity in malignant mesothelioma. Oncotarget. 2016.
    3. Utsumi F, Kajiyama H, Nakamura K, Tanaka H, Mizuno M, Toyokuni S, Hori M, Kikkawa F. Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated medium. Oncol Rep. 2016; 35: 3169-77.
    4. Tsuzuki Y, Yamashita Y, Hattori Y, Hua Li G, Akatsuka S, Kotani T, Kikkawa F, Naiki-Ito A, Takahashi S, Nishiwaki K, Toyokuni S. Pain-reducing anesthesia prevents oxidative stress in human term placenta. J Clin Biochem Nutr. 2016; 58: 156-60.
    5. Toyokuni S. The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis-resistance to non-thermal plasma therapy. Pathol Int. 2016; 66: 245-59.
    6. Toyokuni S. Oxidative stress as an iceberg in carcinogenesis and cancer biology. Arch Biochem Biophys. 2016; 595: 46-9.
    7. Shi L, Wang Y, Ito F, Okazaki Y, Tanaka H, Mizuno M, Hori M, Richardson DR, Toyokuni S. Biphasic effects of l-ascorbate on the tumoricidal activity of non-thermal plasma against malignant mesothelioma cells. Arch Biochem Biophys. 2016; 605: 109-16.
    8. Lin Y, Ohkawara B, Ito M, Misawa N, Miyamoto K, Takegami Y, Masuda A, Toyokuni S, Ohno K. Molecular hydrogen suppresses activated Wnt/beta-catenin signaling. Sci Rep. 2016; 6: 31986.
    9. Kambe T, Fukada T, Toyokuni S. Editorial: The cutting edge of zinc biology. Arch Biochem Biophys. 2016.
    10. Kalinowski DS, Stefani C, Toyokuni S, Ganz T, Anderson GJ, Subramaniam NV, Trinder D, Olynyk JK, Chua A, Jansson PJ, Sahni S, Lane DJ, Merlot AM, Kovacevic Z, Huang ML, Lee CS, Richardson DR. Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics. Biochim Biophys Acta. 2016; 1863: 727-48.
    11. Jiang L, Chew SH, Nakamura K, Ohara Y, Akatsuka S, Toyokuni S. Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis. Cancer Sci. 2016; 107: 908-15.
    12. Ito F, Nishiyama T, Shi L, Mori M, Hirayama T, Nagasawa H, Yasui H, Toyokuni S. Contrasting intra- and extracellular distribution of catalytic ferrous iron in ovalbumin-induced peritonitis. Biochem Biophys Res Commun. 2016; 476: 600-6.
    13. Ishida C, Mori M, Nakamura K, Tanaka H, Mizuno M, Hori M, Iwase A, Kikkawa F, Toyokuni S. Non-thermal plasma prevents progression of endometriosis in mice. Free Radic Res. 2016: 1-9.
    14. Imai K, Kotani T, Tsuda H, Mano Y, Nakano T, Ushida T, Li H, Miki R, Sumigama S, Iwase A, Hirakawa A, Ohno K, Toyokuni S, Takeuchi H, Mizuno T, Suzumura A, Kikkawa F. Neuroprotective potential of molecular hydrogen against perinatal brain injury via suppression of activated microglia. Free Radic Biol Med. 2016; 91: 154-63.
    15. Hori M, Choi EH, Toyokuni S. Low-temperature plasma in biology and medicine. Arch Biochem Biophys. 2016; 605: 1-2.
    16. Hirako S, Tsuda H, Kotani T, Sumigama S, Mano Y, Nakano T, Imai K, Li H, Toyokuni S, Kikkawa F. Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia. Phytother Res. 2016; 30: 1474-80.
    17. Forman HJ, Toyokuni S. Tribute issue: Helmut Sies and oxidative stress: Venit, vidit, vicit. Arch Biochem Biophys. 2016; 595: 2.
    18. Cahill MA, Jazayeri JA, Catalano SM, Toyokuni S, Kovacevic Z, Richardson DR. The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology. Biochim Biophys Acta. 2016.
  • 2015
    1. Yamashita Y, Nagasaka T, Naiki-Ito A, Sato S, Suzuki S, Toyokuni S, Ito M, Takahashi S. Napsin A is a specific marker for ovarian clear cell adenocarcinoma. Mod Pathol. 2015; 28: 111-7.
    2. Yamashita K, Nagai H, Toyokuni S. Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers. Lab Invest. 2015; 95: 749-64.
    3. Toyokuni S, Jiang LI, Kitaura R, Shinohara H. Minimal inflammogenicity of pristine single-wall carbon nanotubes. Nagoya J Med Sci. 2015; 77: 195-202.
    4. Toyokuni S, Jiang L, Wang S, Hirao A, Wada T, Soh C, Toyama K, Kawada A. Aging rather than sun exposure is a major determining factor for the density of miR-125b-positive epidermal stem cells in human skin. Pathol Int. 2015; 65: 415-9.
    5. Nakano T, Kotani T, Mano Y, Tsuda H, Imai K, Ushida T, Li H, Miki R, Sumigama S, Sato Y, Iwase A, Hirakawa A, Asai M, Toyokuni S, Kikkawa F. Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury. J Clin Biochem Nutr. 2015; 57: 178-82.
    6. Mori M, Ito F, Shi L, Wang Y, Ishida C, Hattori Y, Niwa M, Hirayama T, Nagasawa H, Iwase A, Kikkawa F, Toyokuni S. Ovarian endometriosis-associated stromal cells reveal persistently high affinity for iron. Redox Biol. 2015; 6: 578-86.
    7. Hattori Y, Mukaide T, Jiang L, Kotani T, Tsuda H, Mano Y, Sumigama S, Hirayama T, Nagasawa H, Kikkawa F, Toyokuni S. Catalytic ferrous iron in amniotic fluid as a predictive marker of human maternal-fetal disorders. J Clin Biochem Nutr. 2015; 56: 57-63.
    8. Hattori Y, Kotani T, Tsuda H, Mano Y, Tu L, Li H, Hirako S, Ushida T, Imai K, Nakano T, Sato Y, Miki R, Sumigama S, Iwase A, Toyokuni S, Kikkawa F. Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury. Free Radic Res. 2015; 49: 1026-37.
    9. Funahashi S, Okazaki Y, Ito D, Asakawa A, Nagai H, Tajima M, Toyokuni S. Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses in inflammatory cells. J Clin Biochem Nutr. 2015; 56: 111-7.
    10. Chew SH, Toyokuni S. Malignant mesothelioma as an oxidative stress-induced cancer: An update. Free Radic Biol Med. 2015; 86: 166-78.
    11. Asano T, Koike M, Sakata S, Takeda Y, Nakagawa T, Hatano T, Ohashi S, Funayama M, Yoshimi K, Asanuma M, Toyokuni S, Mochizuki H, Uchiyama Y, Hattori N, Iwai K. Possible involvement of iron-induced oxidative insults in neurodegeneration. Neurosci Lett. 2015; 588: 29-35.
  • 2014
    1. Yoshihara M, Jiang L, Akatsuka S, Suyama M, Toyokuni S. Genome-wide profiling of 8-oxoguanine reveals its association with spatial positioning in nucleus. DNA Res. 2014; 21: 603-12.
    2. Yamashita Y, Ito Y, Isomura H, Takemura N, Okamoto A, Motomura K, Tsujiuchi T, Natsume A, Wakabayashi T, Toyokuni S, Tsurumi T. Lack of presence of the human cytomegalovirus in human glioblastoma. Mod Pathol. 2014; 27: 922-9.
    3. Toyokuni S. Iron overload as a major targetable pathogenesis of asbestos-induced mesothelial carcinogenesis. Redox Rep. 2014; 19: 1-7.
    4. Toyokuni S. Iron and thiols as two major players in carcinogenesis: friends or foes? Front Pharmacol. 2014; 5: 200.
    5. Shinjo K, Yamashita Y, Yamamoto E, Akatsuka S, Uno N, Kamiya A, Niimi K, Sakaguchi Y, Nagasaka T, Takahashi T, Shibata K, Kajiyama H, Kikkawa F, Toyokuni S. Expression of chromobox homolog 7 (CBX7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via TRAIL-induced apoptotic pathway regulation. Int J Cancer. 2014; 135: 308-18.
    6. Okazaki Y, Wang Y, Tanaka H, Mizuno M, Nakamura K, Kajiyama H, Kano H, Uchida K, Kikkawa F, Hori M, Toyokuni S. Direct exposure of non-equilibrium atmospheric pressure plasma confers simultaneous oxidative and ultraviolet modifications in biomolecules. J Clin Biochem Nutr. 2014; 55: 207-15.
    7. Nishiwaki S, Nakayama T, Murata M, Nishida T, Terakura S, Saito S, Kato T, Mizuno H, Imahashi N, Seto A, Ozawa Y, Miyamura K, Ito M, Takeshita K, Kato H, Toyokuni S, Nagao K, Ueda R, Naoe T. Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions. PLoS One. 2014; 9: e96252.
    8. Mukaide T, Hattori Y, Misawa N, Funahashi S, Jiang L, Hirayama T, Nagasawa H, Toyokuni S. Histological detection of catalytic ferrous iron with the selective turn-on fluorescent probe RhoNox-1 in a Fenton reaction-based rat renal carcinogenesis model. Free Radic Res. 2014; 48: 990-5.
    9. Mano Y, Kotani T, Ito M, Nagai T, Ichinohashi Y, Yamada K, Ohno K, Kikkawa F, Toyokuni S. Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion. Free Radic Biol Med. 2014; 69: 324-30.
    10. Jiang L, Yamashita Y, Chew SH, Akatsuka S, Ukai S, Wang S, Nagai H, Okazaki Y, Takahashi T, Toyokuni S. Connective tissue growth factor and beta-catenin constitute an autocrine loop for activation in rat sarcomatoid mesothelioma. J Pathol. 2014; 233: 402-14.
    11. Handa O, Naito Y, Toyokuni S. As a host society to SFRRI 2014 in Kyoto. J Clin Biochem Nutr. 2014; 54: 1.
    12. Fujii K, Yamashita Y, Yamamoto T, Takahashi K, Hashimoto K, Miyata T, Kawai K, Kikkawa F, Toyokuni S, Nagasaka T. Ovarian mucinous tumors arising from mature cystic teratomas--a molecular genetic approach for understanding the cellular origin. Hum Pathol. 2014; 45: 717-24.
    13. Chew SH, Okazaki Y, Nagai H, Misawa N, Akatsuka S, Yamashita K, Jiang L, Yamashita Y, Noguchi M, Hosoda K, Sekido Y, Takahashi T, Toyokuni S. Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production. Carcinogenesis. 2014; 35: 164-72.
    14. Aierken D, Okazaki Y, Chew SH, Sakai A, Wang Y, Nagai H, Misawa N, Kohyama N, Toyokuni S. Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis. Nagoya J Med Sci. 2014; 76: 149-60.
  • 2013
    1. Yamazaki K, Tanaka S, Sakata R, Miwa S, Oriyanhan W, Takaba K, Minakata K, Marui A, Ikeda T, Toyokuni S, Komeda M, Ueda K. Protective effect of cardioplegia with poly (ADP-ribose) polymerase-1 inhibitor against myocardial ischemia-reperfusion injury: in vitro study of isolated rat heart model. J Enzyme Inhib Med Chem. 2013; 28: 143-7.
    2. Yamashita Y, Akatsuka S, Shinjo K, Yatabe Y, Kobayashi H, Seko H, Kajiyama H, Kikkawa F, Takahashi T, Toyokuni S. Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis. PLoS One. 2013; 8: e57724.
    3. Yamashita K, Nagai H, Kondo Y, Misawa N, Toyokuni S. Evaluation of two distinct methods to quantify the uptake of crocidolite fibers by mesothelial cells. J Clin Biochem Nutr. 2013; 53: 27-35.
    4. Toyokuni S. Genotoxicity and carcinogenicity risk of carbon nanotubes. Adv Drug Deliv Rev. 2013; 65: 2098-110.
    5. Okazaki Y, Nagai H, Chew SH, Li J, Funahashi S, Tsujimura T, Toyokuni S. CD146 and insulin-like growth factor 2 mRNA-binding protein 3 predict prognosis of asbestos-induced rat mesothelioma. Cancer Sci. 2013; 104: 989-95.
    6. Nagai H, Okazaki Y, Chew SH, Misawa N, Yasui H, Toyokuni S. Deferasirox induces mesenchymal-epithelial transition in crocidolite-induced mesothelial carcinogenesis in rats. Cancer Prev Res (Phila). 2013; 6: 1222-30.
    7. Nagai H, Okazaki Y, Chew SH, Misawa N, Miyata Y, Shinohara H, Toyokuni S. Intraperitoneal administration of tangled multiwalled carbon nanotubes of 15 nm in diameter does not induce mesothelial carcinogenesis in rats. Pathol Int. 2013; 63: 457-62.
    8. Nagai H, Chew SH, Okazaki Y, Funahashi S, Namba T, Kato T, Enomoto A, Jiang L, Akatsuka S, Toyokuni S. Metamorphosis of mesothelial cells with active horizontal motility in tissue culture. Sci Rep. 2013; 3: 1144.
    9. Hotta H, Hamamura K, Yamashita K, Shibuya H, Tokuda N, Hashimoto N, Furukawa K, Yamamoto N, Hattori H, Toyokuni S, Ueda M, Furukawa K. Lewis y antigen is expressed in oral squamous cell carcinoma cell lines and tissues, but disappears in the invasive regions leading to the enhanced malignant properties irrespective of sialyl-Lewis x. Glycoconj J. 2013; 30: 585-97.
    10. Hamakawa M, Ishida A, Tamakoshi K, Shimada H, Nakashima H, Noguchi T, Toyokuni S, Ishida K. Repeated short-term daily exercise ameliorates oxidative cerebral damage and the resultant motor dysfunction after transient ischemia in rats. J Clin Biochem Nutr. 2013; 53: 8-14.
    11. Chikazawa M, Otaki N, Shibata T, Miyashita H, Kawai Y, Maruyama S, Toyokuni S, Kitaura Y, Matsuda T, Uchida K. Multispecificity of immunoglobulin M antibodies raised against advanced glycation end products: involvement of electronegative potential of antigens. J Biol Chem. 2013; 288: 13204-14.
  • 2012
    1. Okazaki Y, Kono I, Kuriki T, Funahashi S, Fushimi S, Iqbal M, Okada S, Toyokuni S. Bovine lactoferrin ameliorates ferric nitrilotriacetate-induced renal oxidative damage in rats. J Clin Biochem Nutr. 2012; 51: 84-90.
    2. Nagai H, Toyokuni S. Differences and similarities between carbon nanotubes and asbestos fibers during mesothelial carcinogenesis: shedding light on fiber entry mechanism. Cancer Sci. 2012; 103: 1378-90.
    3. Morimoto H, Lee J, Tanaka T, Ishii K, Toyokuni S, Kanatsu-Shinohara M, Shinohara T. In vitro transformation of mouse testis cells by oncogene transfection. Biol Reprod. 2012; 86: 148, 1-11.
    4. Mizuno T, Murakami H, Fujii M, Ishiguro F, Tanaka I, Kondo Y, Akatsuka S, Toyokuni S, Yokoi K, Osada H, Sekido Y. YAP induces malignant mesothelioma cell proliferation by upregulating transcription of cell cycle-promoting genes. Oncogene. 2012; 31: 5117-22.
    5. Majima HJ, Toyokuni S. Mitochondria and free radical studies on health, disease and pollution. Free Radic Res. 2012; 46: 925-6.
    6. Kubo Y, Takenaka H, Nagai H, Toyokuni S. Distinct affinity of nuclear proteins to the surface of chrysotile and crocidolite. J Clin Biochem Nutr. 2012; 51: 221-6.
    7. Kobayashi H, Yamashita Y, Iwase A, Yoshikawa Y, Yasui H, Kawai Y, Uchida K, Uno N, Akatsuka S, Takahashi T, Kikkawa F, Toyokuni S. The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis. Fertil Steril. 2012; 98: 415-22 e1-12.
    8. Jiang L, Akatsuka S, Nagai H, Chew SH, Ohara H, Okazaki Y, Yamashita Y, Yoshikawa Y, Yasui H, Ikuta K, Sasaki K, Kohgo Y, Hirano S, Shinohara Y, Kohyama N, Takahashi T, Toyokuni S. Iron overload signature in chrysotile-induced malignant mesothelioma. J Pathol. 2012; 228: 366-77.
    9. Ishii K, Kanatsu-Shinohara M, Toyokuni S, Shinohara T. FGF2 mediates mouse spermatogonial stem cell self-renewal via upregulation of Etv5 and Bcl6b through MAP2K1 activation. Development. 2012; 139: 1734-43.
    10. Horio M, Sato M, Takeyama Y, Elshazley M, Yamashita R, Hase T, Yoshida K, Usami N, Yokoi K, Sekido Y, Kondo M, Toyokuni S, Gazdar AF, Minna JD, Hasegawa Y. Transient but not stable ZEB1 knockdown dramatically inhibits growth of malignant pleural mesothelioma cells. Ann Surg Oncol. 2012; 19 Suppl 3: S634-45.
    11. Elshazley M, Sato M, Hase T, Yamashita R, Yoshida K, Toyokuni S, Ishiguro F, Osada H, Sekido Y, Yokoi K, Usami N, Shames DS, Kondo M, Gazdar AF, Minna JD, Hasegawa Y. The circadian clock gene BMAL1 is a novel therapeutic target for malignant pleural mesothelioma. Int J Cancer. 2012; 131: 2820-31.
    12. Akatsuka S, Yamashita Y, Ohara H, Liu YT, Izumiya M, Abe K, Ochiai M, Jiang L, Nagai H, Okazaki Y, Murakami H, Sekido Y, Arai E, Kanai Y, Hino O, Takahashi T, Nakagama H, Toyokuni S. Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer. PLoS One. 2012; 7: e43403.
    13. Akatsuka S, Toyokuni S. Genome-wide assessment of oxidatively generated DNA damage. Free Radic Res. 2012; 46: 523-30.
  • 2011
    1. Yamashita Y, Kajiura D, Tang L, Hasegawa Y, Kinoshita T, Nakamura S, Akatsuka S, Toyokuni S, Mori N. XCR1 expression and biased VH gene usage are distinct features of diffuse large B-cell lymphoma initially manifesting in the bone marrow. Am J Clin Pathol. 2011; 135: 556-64.
    2. Toyokuni S, Hirao A, Wada T, Nagai R, Date A, Yoshii T, Akatsuka S, Yamashita Y, Kawada A. Age- and sun exposure-dependent differences in 8-hydroxy-2'-deoxyguanosine and N-(carboxymethyl)lysine in human epidermis. J Clin Biochem Nutr. 2011; 49: 121-4.
    3. Toyokuni S. Mysterious link between iron overload and CDKN2A/2B. J Clin Biochem Nutr. 2011; 48: 46-9.
    4. Toyokuni S. Iron as a target of chemoprevention for longevity in humans. Free Radic Res. 2011; 45: 906-17.
    5. Ohara H, Akatsuka S, Nagai H, Liu YT, Jiang L, Okazaki Y, Yamashita Y, Nakamura T, Toyokuni S. Stage-specific roles of fibulin-5 during oxidative stress-induced renal carcinogenesis in rats. Free Radic Res. 2011; 45: 211-20.
    6. Nishikawa E, Osada H, Okazaki Y, Arima C, Tomida S, Tatematsu Y, Taguchi A, Shimada Y, Yanagisawa K, Yatabe Y, Toyokuni S, Sekido Y, Takahashi T. miR-375 is activated by ASH1 and inhibits YAP1 in a lineage-dependent manner in lung cancer. Cancer Res. 2011; 71: 6165-73.
    7. Nagai H, Okazaki Y, Chew SH, Misawa N, Yamashita Y, Akatsuka S, Ishihara T, Yamashita K, Yoshikawa Y, Yasui H, Jiang L, Ohara H, Takahashi T, Ichihara G, Kostarelos K, Miyata Y, Shinohara H, Toyokuni S. Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis. Proc Natl Acad Sci U S A. 2011; 108: E1330-8.
    8. Nagai H, Ishihara T, Lee WH, Ohara H, Okazaki Y, Okawa K, Toyokuni S. Asbestos surface provides a niche for oxidative modification. Cancer Sci. 2011; 102: 2118-25.
    9. Murakami H, Mizuno T, Taniguchi T, Fujii M, Ishiguro F, Fukui T, Akatsuka S, Horio Y, Hida T, Kondo Y, Toyokuni S, Osada H, Sekido Y. LATS2 is a tumor suppressor gene of malignant mesothelioma. Cancer Res. 2011; 71: 873-83.
  • 2010
    1. Toyokuni S. Toward a new era of the Nagoya journal of medical science: message from the new editor-in-chief. Nagoya J Med Sci. 2010; 72: 107-9.
    2. Shirase T, Mori K, Okazaki Y, Itoh K, Yamamoto M, Tabuchi M, Kishi F, Jiang L, Akatsuka S, Nakao K, Toyokuni S. Suppression of SLC11A2 expression is essential to maintain duodenal integrity during dietary iron overload. Am J Pathol. 2010; 177: 677-85.
    3. Okazaki Y, Iqbal M, Kawakami N, Yamamoto Y, Toyokuni S, Okada S. A beverage containing fermented black soybean ameliorates ferric nitrilotriacetate-induced renal oxidative damage in rats. J Clin Biochem Nutr. 2010; 47: 198-207.
    4. Nagai H, Toyokuni S. Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials. Arch Biochem Biophys. 2010; 502: 1-7.
    5. Jiang L, Yamashita Y, Toyokuni S. A novel method for efficient collection of normal mesothelial cells in vivo. J Clin Biochem Nutr. 2010; 46: 265-8.
    6. Ishino K, Wakita C, Shibata T, Toyokuni S, Machida S, Matsuda S, Matsuda T, Uchida K. Lipid peroxidation generates body odor component trans-2-nonenal covalently bound to protein in vivo. J Biol Chem. 2010; 285: 15302-13.
    7. Hu Q, Akatsuka S, Yamashita Y, Ohara H, Nagai H, Okazaki Y, Takahashi T, Toyokuni S. Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma. Lab Invest. 2010; 90: 360-73.
    8. Akatsuka S, Toyokuni S. Genome-scale approaches to investigate oxidative DNA damage. J Clin Biochem Nutr. 2010; 47: 91-7.
  • 2009
    1. Zhong Y, Onuki J, Yamasaki T, Ogawa O, Akatsuka S, Toyokuni S. Genome-wide analysis identifies a tumor suppressor role for aminoacylase 1 in iron-induced rat renal cell carcinoma. Carcinogenesis. 2009; 30: 158-64.
    2. Toyokuni S. Role of iron in carcinogenesis: cancer as a ferrotoxic disease. Cancer Sci. 2009; 100: 9-16.
    3. Toyokuni S. Mechanisms of asbestos-induced carcinogenesis. Nagoya J Med Sci. 2009; 71: 1-10.
    4. Takashima S, Takehashi M, Lee J, Chuma S, Okano M, Hata K, Suetake I, Nakatsuji N, Miyoshi H, Tajima S, Tanaka Y, Toyokuni S, Sasaki H, Kanatsu-Shinohara M, Shinohara T. Abnormal DNA methyltransferase expression in mouse germline stem cells results in spermatogenic defects. Biol Reprod. 2009; 81: 155-64.
    5. Lee J, Kanatsu-Shinohara M, Morimoto H, Kazuki Y, Takashima S, Oshimura M, Toyokuni S, Shinohara T. Genetic reconstruction of mouse spermatogonial stem cell self-renewal in vitro by Ras-cyclin D2 activation. Cell Stem Cell. 2009; 5: 76-86.
    6. Hiraumi Y, Iwai-Kanai E, Baba S, Yui Y, Kamitsuji Y, Mizushima Y, Matsubara H, Watanabe M, Watanabe K, Toyokuni S, Matsubara H, Nakahata T, Adachi S. Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury. Am J Physiol Heart Circ Physiol. 2009; 296: H823-32.
  • 2008
    1. Yamaguchi K, Mandai M, Toyokuni S, Hamanishi J, Higuchi T, Takakura K, Fujii S. Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Clin Cancer Res. 2008; 14: 32-40.
    2. Toyokuni S. Molecular mechanisms of oxidative stress-induced carcinogenesis: from epidemiology to oxygenomics. IUBMB Life. 2008; 60: 441-7.
    3. Jiang L, Nagai H, Ohara H, Hara S, Tachibana M, Hirano S, Shinohara Y, Kohyama N, Akatsuka S, Toyokuni S. Characteristics and modifying factors of asbestos-induced oxidative DNA damage. Cancer Sci. 2008; 99: 2142-51.
    4. Ishino K, Shibata T, Ishii T, Liu YT, Toyokuni S, Zhu X, Sayre LM, Uchida K. Protein N-acylation: H2O2-mediated covalent modification of protein by lipid peroxidation-derived saturated aldehydes. Chem Res Toxicol. 2008; 21: 1261-70.
  • 2007
    1. Zhong Y, Jiang L, Hiai H, Toyokuni S, Yamada Y. Overexpression of a transcription factor LYL1 induces T- and B-cell lymphoma in mice. Oncogene. 2007; 26: 6937-47.
    2. Toyokuni S, Akatsuka S. Pathological investigation of oxidative stress in the post-genomic era. Pathol Int. 2007; 57: 461-73.
    3. Miyagawa-Hayashino A, Tsuruyama T, Egawa H, Haga H, Sakashita H, Okuno T, Toyokuni S, Tamaki K, Yamabe H, Manabe T, Uemoto S. FasL expression in hepatic antigen-presenting cells and phagocytosis of apoptotic T cells by FasL+ Kupffer cells are indicators of rejection activity in human liver allografts. Am J Pathol. 2007; 171: 1499-508.
    4. Liu YT, Shang D, Akatsuka S, Ohara H, Dutta KK, Mizushima K, Naito Y, Yoshikawa T, Izumiya M, Abe K, Nakagama H, Noguchi N, Toyokuni S. Chronic oxidative stress causes amplification and overexpression of ptprz1 protein tyrosine phosphatase to activate beta-catenin pathway. Am J Pathol. 2007; 171: 1978-88.
    5. Kanatsu-Shinohara M, Inoue K, Ogonuki N, Miki H, Yoshida S, Toyokuni S, Lee J, Ogura A, Shinohara T. Leukemia inhibitory factor enhances formation of germ cell colonies in neonatal mouse testis culture. Biol Reprod. 2007; 76: 55-62.
    6. Dutta KK, Zhong Y, Liu YT, Yamada T, Akatsuka S, Hu Q, Yoshihara M, Ohara H, Takehashi M, Shinohara T, Masutani H, Onuki J, Toyokuni S. Association of microRNA-34a overexpression with proliferation is cell type-dependent. Cancer Sci. 2007; 98: 1845-52.
  • 2006
    1. Toyokuni S, Yasui H, Date A, Hakozaki T, Akatsuka S, Kohda H, Yoshii T, Sakurai H. Novel screening method for ultraviolet protection: combination of a human skin-equivalent model and 8-hydroxy-2'-deoxyguanosine. Pathol Int. 2006; 56: 760-2.
    2. Toyokuni S. Novel aspects of oxidative stress-associated carcinogenesis. Antioxid Redox Signal. 2006; 8: 1373-7.
    3. Akatsuka S, Aung TT, Dutta KK, Jiang L, Lee WH, Liu YT, Onuki J, Shirase T, Yamasaki K, Ochi H, Naito Y, Yoshikawa T, Kasai H, Tominaga Y, Sakumi K, Nakabeppu Y, Kawai Y, Uchida K, Yamasaki A, Tsuruyama T, Yamada Y, Toyokuni S. Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified adenine during oxidative stress-induced renal carcinogenesis. Am J Pathol. 2006; 169: 1328-42.
  • 2005
    1. Ozeki M, Miyagawa-Hayashino A, Akatsuka S, Shirase T, Lee WH, Uchida K, Toyokuni S. Susceptibility of actin to modification by 4-hydroxy-2-nonenal. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; 827: 119-26.
    2. Dutta KK, Nishinaka Y, Masutani H, Akatsuka S, Aung TT, Shirase T, Lee WH, Yamada Y, Hiai H, Yodoi J, Toyokuni S. Two distinct mechanisms for loss of thioredoxin-binding protein-2 in oxidative stress-induced renal carcinogenesis. Lab Invest. 2005; 85: 798-807.
  • 2004
    1. Toyokuni S. Redox control of carcinogenesis and tumor biology. Antioxid Redox Signal. 2004; 6: 481-2.
    2. Tanaka T, Akatsuka S, Ozeki M, Shirase T, Hiai H, Toyokuni S. Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis. Oncogene. 2004; 23: 3980-9.
    3. Okumura H, Nagaya N, Itoh T, Okano I, Hino J, Mori K, Tsukamoto Y, Ishibashi-Ueda H, Miwa S, Tambara K, Toyokuni S, Yutani C, Kangawa K. Adrenomedullin infusion attenuates myocardial ischemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway. Circulation. 2004; 109: 242-8.
    4. Okada M, Adachi S, Imai T, Watanabe K, Toyokuni SY, Ueno M, Zervos AS, Kroemer G, Nakahata T. A novel mechanism for imatinib mesylate-induced cell death of BCR-ABL-positive human leukemic cells: caspase-independent, necrosis-like programmed cell death mediated by serine protease activity. Blood. 2004; 103: 2299-307.
    5. Nishigori C, Hattori Y, Toyokuni S. Role of reactive oxygen species in skin carcinogenesis. Antioxid Redox Signal. 2004; 6: 561-70.
    6. Minamiyama Y, Takemura S, Toyokuni S, Imaoka S, Funae Y, Hirohashi K, Yoshikawa T, Okada S. CYP3A induction aggravates endotoxemic liver injury via reactive oxygen species in male rats. Free Radic Biol Med. 2004; 37: 703-12.
    7. Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O, Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T. Generation of pluripotent stem cells from neonatal mouse testis. Cell. 2004; 119: 1001-12.
    8. Hiroyasu M, Akatsuka S, Shirase T, Toda Y, Hiai H, Toyokuni S. Detection of glyceraldehyde 3-phosphate dehydrogenase messenger RNA using a peptide nucleic acid probe in paraffin-embedded archival specimens. Pathol Int. 2004; 54: 251-5.
  • 2003
    1. Toyokuni S, Tanaka T, Kawaguchi W, Fang NR, Ozeki M, Akatsuka S, Hiai H, Aruoma OI, Bahorun T. Effects of the phenolic contents of Mauritian endemic plant extracts on promoter activities of antioxidant enzymes. Free Radic Res. 2003; 37: 1215-24.
    2. Toyokuni S, Kawaguchi W, Akatsuka S, Hiroyasu M, Hiai H. Intermittent microwave irradiation facilitates antigen-antibody reaction in Western blot analysis. Pathol Int. 2003; 53: 259-61.
    3. Narushima S, Spitz DR, Oberley LW, Toyokuni S, Miyata T, Gunnett CA, Buettner GR, Zhang J, Ismail H, Lynch RG, Berg DJ. Evidence for oxidative stress in NSAID-induced colitis in IL10-/- mice. Free Radic Biol Med. 2003; 34: 1153-66.
    4. Kuroda K, Han H, Tani S, Tanigaki K, Tun T, Furukawa T, Taniguchi Y, Kurooka H, Hamada Y, Toyokuni S, Honjo T. Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway. Immunity. 2003; 18: 301-12.
    5. Hashimoto M, Sibata T, Wasada H, Toyokuni S, Uchida K. Structural basis of protein-bound endogenous aldehydes. Chemical and immunochemical characterizations of configurational isomers of a 4-hydroxy-2-nonenal-histidine adduct. J Biol Chem. 2003; 278: 5044-51.
    6. Aoi W, Naito Y, Sakuma K, Kuchide M, Tokuda H, Maoka T, Toyokuni S, Oka S, Yasuhara M, Yoshikawa T. Astaxanthin limits exercise-induced skeletal and cardiac muscle damage in mice. Antioxid Redox Signal. 2003; 5: 139-44.
  • 2002
    1. Yamagami K, Yamamoto Y, Toyokuni S, Hata K, Yamaoka Y. Heat shock preconditioning reduces the formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal modified proteins in ischemia-reperfused liver of rats. Free Radic Res. 2002; 36: 169-76.
    2. Toyokuni S. Iron and carcinogenesis: from Fenton reaction to target genes. Redox Rep. 2002; 7: 189-97.
    3. Nakamura K, Kusano K, Nakamura Y, Kakishita M, Ohta K, Nagase S, Yamamoto M, Miyaji K, Saito H, Morita H, Emori T, Matsubara H, Toyokuni S, Ohe T. Carvedilol decreases elevated oxidative stress in human failing myocardium. Circulation. 2002; 105: 2867-71.
    4. Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, Fujimoto S, Oku A, Tsuda K, Toyokuni S, Hiai H, Mizunoya W, Fushiki T, Holst JJ, Makino M, Tashita A, Kobara Y, Tsubamoto Y, Jinnouchi T, Jomori T, Seino Y. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002; 8: 738-42.
    5. Miwa S, Toyokuni S, Nishina T, Nomoto T, Hiroyasu M, Nishimura K, Komeda M. Spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine levels in cardiomyocytes after myocardial infarction in rats. Free Radic Res. 2002; 36: 853-8.
    6. Kondo S, Toyokuni S, Tsuruyama T, Ozeki M, Tachibana T, Echizenya M, Hiai H, Onodera H, Imamura M. Peroxynitrite-mediated stress is associated with proliferation of human metastatic colorectal carcinoma in the liver. Cancer Lett. 2002; 179: 87-93.
    7. Kanatsu-Shinohara M, Ogura A, Ikegawa M, Inoue K, Ogonuki N, Tashiro K, Toyokuni S, Honjo T, Shinohara T. Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice. Proc Natl Acad Sci U S A. 2002; 99: 1383-8.
    8. Hiroyasu M, Ozeki M, Miyagawa-Hayashino A, Fujiwara Y, Hiai H, Toyokuni S. Novel surrogate end-point biomarker to evaluate agents for use in the chemoprevention of reactive oxygen species-associated cancer. Redox Rep. 2002; 7: 335-8.
    9. Hiroyasu M, Ozeki M, Kohda H, Echizenya M, Tanaka T, Hiai H, Toyokuni S. Specific allelic loss of p16 (INK4A) tumor suppressor gene after weeks of iron-mediated oxidative damage during rat renal carcinogenesis. Am J Pathol. 2002; 160: 419-24.
    10. Ban N, Yamada Y, Someya Y, Miyawaki K, Ihara Y, Hosokawa M, Toyokuni S, Tsuda K, Seino Y. Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter. Diabetes. 2002; 51: 1409-18.
  • 2001
    1. Toyokuni S, Masumizu T, Ozeki M, Kondo S, Hiroyasu M, Kohno M, Hiai H. An electron spin resonance study on alkylperoxyl radical in thin-sliced renal tissues from ferric nitrilotriacetate-treated rats: the effect of alpha-tocopherol feeding. Free Radic Res. 2001; 35: 245-55.
    2. Mori M, Toyokuni S, Kondo S, Kasai H, Naiki H, Toichi E, Hosokawa M, Higuchi K. Spontaneous loss-of-function mutations of the 8-oxoguanine DNA glycosylase gene in mice and exploration of the possible implication of the gene in senescence. Free Radic Biol Med. 2001; 30: 1130-6.
  • 2000
    1. Yamagami K, Yamamoto Y, Kume M, Ishikawa Y, Yamaoka Y, Hiai H, Toyokuni S. Formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in rat liver after ischemia-reperfusion: distinct localization of the two oxidatively modified products. Antioxid Redox Signal. 2000; 2: 127-36.
    2. Toyokuni S, Yamada S, Kashima M, Ihara Y, Yamada Y, Tanaka T, Hiai H, Seino Y, Uchida K. Serum 4-hydroxy-2-nonenal-modified albumin is elevated in patients with type 2 diabetes mellitus. Antioxid Redox Signal. 2000; 2: 681-5.
    3. Tanaka T, Kondo S, Iwasa Y, Hiai H, Toyokuni S. Expression of stress-response and cell proliferation genes in renal cell carcinoma induced by oxidative stress. Am J Pathol. 2000; 156: 2149-57.
    4. Kondo S, Toyokuni S, Tanaka T, Hiai H, Onodera H, Kasai H, Imamura M. Overexpression of the hOGG1 gene and high 8-hydroxy-2'-deoxyguanosine (8-OHdG) lyase activity in human colorectal carcinoma: regulation mechanism of the 8-OHdG level in DNA. Clin Cancer Res. 2000; 6: 1394-400.
  • 1999
    1. Toyokuni S. Reactive oxygen species-induced molecular damage and its application in pathology. Pathol Int. 1999; 49: 91-102.
    2. Tanaka T, Iwasa Y, Kondo S, Hiai H, Toyokuni S. High incidence of allelic loss on chromosome 5 and inactivation of p15INK4B and p16INK4A tumor suppressor genes in oxystress-induced renal cell carcinoma of rats. Oncogene. 1999; 18: 3793-7.
  • 1997
    1. Toyokuni S, Tanaka T, Hattori Y, Nishiyama Y, Yoshida A, Uchida K, Hiai H, Ochi H, Osawa T. Quantitative immunohistochemical determination of 8-hydroxy-2'-deoxyguanosine by a monoclonal antibody N45.1: its application to ferric nitrilotriacetate-induced renal carcinogenesis model. Lab Invest. 1997; 76: 365-74.
    2. Toyokuni S, Luo XP, Tanaka T, Uchida K, Hiai H, Lehotay DC. Induction of a wide range of C(2-12) aldehydes and C(7-12) acyloins in the kidney of Wistar rats after treatment with a renal carcinogen, ferric nitrilotriacetate. Free Radic Biol Med. 1997; 22: 1019-27.
  • 1996
    1. Toyokuni S. Iron-induced carcinogenesis: the role of redox regulation. Free Radic Biol Med. 1996; 20: 553-66.
    2. Okamoto K, Toyokuni S, Kim WJ, Ogawa O, Kakehi Y, Arao S, Hiai H, Yoshida O. Overexpression of human mutT homologue gene messenger RNA in renal-cell carcinoma: evidence of persistent oxidative stress in cancer. Int J Cancer. 1996; 65: 437-41.
    3. Hattori Y, Nishigori C, Tanaka T, Uchida K, Nikaido O, Osawa T, Hiai H, Imamura S, Toyokuni S. 8-hydroxy-2'-deoxyguanosine is increased in epidermal cells of hairless mice after chronic ultraviolet B exposure. J Invest Dermatol. 1996; 107: 733-7.
    4. Fukuda A, Osawa T, Oda H, Toyokuni S, Satoh K, Uchida K. Oxidative stress response in iron-induced renal carcinogenesis: acute nephrotoxicity mediates the enhanced expression of glutathione S-transferase Yp isozyme. Arch Biochem Biophys. 1996; 329: 39-46.
    5. Fukuda A, Osawa T, Oda H, Tanaka T, Toyokuni S, Uchida K. Oxidative stress response in iron-induced acute nephrotoxicity: enhanced expression of heat shock protein 90. Biochem Biophys Res Commun. 1996; 219: 76-81.
  • 1995
    1. Uchida K, Osawa T, Hiai H, Toyokuni S. 4-Hydroxy-2-nonenal-trapping ELISA: direct evidence for the release of a cytotoxic aldehyde from oxidized low density lipoproteins. Biochem Biophys Res Commun. 1995; 212: 1068-73.
    2. Uchida K, Itakura K, Kawakishi S, Hiai H, Toyokuni S, Stadtman ER. Characterization of epitopes recognized by 4-hydroxy-2-nonenal specific antibodies. Arch Biochem Biophys. 1995; 324: 241-8.
    3. Uchida K, Fukuda A, Kawakishi S, Toyokuni S, Hiai H, Ikeda S, Horio F. Acute nephrotoxicity of a carcinogenic iron chelate. Selective inhibition of a proteolytic conversion of alpha 2U-globulin to the kidney fatty acid-binding protein. FEBS Lett. 1995; 357: 165-7.
  • 1994
    1. Toyokuni S, Uchida K, Okamoto K, Hattori-Nakakuki Y, Hiai H, Stadtman ER. Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate. Proc Natl Acad Sci U S A. 1994; 91: 2616-20.
  • 1990
    1. Toyokuni S, Okada S, Hamazaki S, Minamiyama Y, Yamada Y, Liang P, Fukunaga Y, Midorikawa O. Combined histochemical and biochemical analysis of sex hormone dependence of ferric nitrilotriacetate-induced renal lipid peroxidation in ddY mice. Cancer Res. 1990; 50: 5574-80.

Research Keywords

Oxidative stress、 iron metabolism、 asbestos、 carbon nanotube、 mesothelioma、 non-thermal plasma、 animal carcinogenesis model、 oxygenomics、 cancer prevention


Financially supported students are welcome for master and PhD courses. We seek for students deeply interested in oxidative stress.