Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology. Reviewed International journal

Cahill MA, Jazayeri JA, Catalano SM, Toyokuni S, Kovacevic Z, Richardson DR

Biochim Biophys Acta. 2016 Jul 22. Vol. pii: S0304-419X ( 16 ) page： 30049-X. 2016.7

[Iron function and carcinogenesis].

Akatsuka S, Toyokuni S

Nihon rinsho. Japanese journal of clinical medicine Vol. 74 ( 7 ) page： 1168 - 75 2016.7

[Iron function and carcinogenesis].

Akatsuka S, Toyokuni S

Nihon rinsho. Japanese journal of clinical medicine Vol. 74 ( 7 ) page： 1168 - 75 2016.7

Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated medium. Reviewed

Vol. 35 ( 6 ) page： 3169-77 2016.6

Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis. Reviewed

Jiang L, Chew SH, Nakamura K, Ohara Y, Akatsuka S, Toyokuni S.

Cancer Sci. 2016 Jul;107(7):908-15. Vol. 107 ( 7 ) page： 908-15 2016.6

Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis. Reviewed International journal

Jiang L, Chew SH, Nakamura K, Ohara Y, Akatsuka S, Toyokuni S

Cancer Sci. 2016 Jul;107(7):908-15. Vol. 107 ( 7 ) page： 908-15 2016.6

Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated medium Reviewed International journal

Fumi Utsumi, Hiroaki Kajiyama, Kae Nakamura, Hiromasa Tanaka, Masaaki Mizuno, Shinnya Toyokuni, Masaru Hori, Fumitaka Kikkawa

ONCOLOGY REPORTS Vol. 35 ( 6 ) page： 3169 - 77 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Non-thermal atmospheric pressure plasma has been widely studied in recent years in many fields, including cancer treatment. However, its efficiency for inducing apoptosis sometimes varies depending on the cell species and experimental conditions. The aim of this study was to elucidate what causes these differences in responses to plasma treatment. Using four ovarian cancer cell lines, the cell density had a markedly negative impact on the proliferation inhibition rate (PIR) and it was more obvious in OVCAR-3 and NOS2 cells. Furthermore, TOV21G and ES-2 cells were drastically sensitive to plasma-activated medium (PAM) compared with the other two cell lines. We demonstrated that the proportion of reactive oxygen species and cell number had a marked impact on the effect of PAM against ovarian cancer cells. Additionally it was suggested that the morphological features of cells were also closely related to the sensitivity of cancer cells to the plasma treatment.

DOI： 10.3892/or.2016.4726

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 Reviewed International journal

Toyokuni S.

Pathology International Vol. 66 ( 5 ) page： 245 - 259 2016.5

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. Invited Reviewed International journal

Toyokuni S

Pathol Int. Vol. 66 ( 5 ) page： 245-259 2016.5

Oxidative stress as an iceberg in carcinogenesis and cancer biology Reviewed International journal

Toyokuni Shinya

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS Vol. 595 page： 46 - 49 2016.4

Oxidative stress as an iceberg in carcinogenesis and cancer biology. Reviewed

Toyokuni S.

Arch Biochem Biophys. 2016 Apr 1;595:46-9. Vol. 595 page： 46-9 2016.4

Oxidative stress as an iceberg in carcinogenesis and cancer biology. Reviewed International journal

Toyokuni S

Arch Biochem Biophys. 2016 Apr 1;595:46-9. Vol. 595 page： 46-9 2016.4

Tribute issue: Helmut Sies and oxidative stress: Venit, vidit, vicit Reviewed International journal

Forman H.

Archives of Biochemistry and Biophysics Vol. 595 2016.4

Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics.

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.

Biochim Biophys Acta. Vol. 1863 ( 4 ) page： 727-748 2016.4

Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics. International journal

Danuta S Kalinowski, Christian Stefani, Shinya Toyokuni, Tomas Ganz, Gregory J Anderson, Nathan V Subramaniam, Debbie Trinder, John K Olynyk, Anita Chua, Patric J Jansson, Sumit Sahni, Darius J R Lane, Angelica M Merlot, Zaklina Kovacevic, Michael L H Huang, C Soon Lee, Des R Richardson

Biochimica et biophysica acta Vol. 1863 ( 4 ) page： 727 - 48 2016.4

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Essential metals, such as iron and copper, play a critical role in a plethora of cellular processes including cell growth and proliferation. However, concomitantly, excess of these metal ions in the body can have deleterious effects due to their ability to generate cytotoxic reactive oxygen species (ROS). Thus, the human body has evolved a very well orchestrated metabolic system that keeps tight control on the levels of these metal ions. Considering their very high proliferation rate, cancer cells require a high abundance of these metals compared to their normal counterparts. Interestingly, new anti-cancer agents that take advantage of the sensitivity of cancer cells to metal sequestration and their susceptibility to ROS have been developed. These ligands can avidly bind metal ions to form redox active metal complexes, which lead to generation of cytotoxic ROS. Furthermore, these agents also act as potent metastasis suppressors due to their ability to up-regulate the metastasis suppressor gene, N-myc downstream regulated gene 1. This review discusses the importance of iron and copper in the metabolism and progression of cancer, how they can be exploited to target tumors and the clinical translation of novel anti-cancer chemotherapeutics. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.bbamcr.2016.01.026

Role of hemoglobin and transferrin in multi-wall carbon nanotube-induced mesothelial injury and carcinogenesis. Reviewed

Wang Y, Okazaki Y, Shi L, Kohda H, Tanaka M, Taki K, Nishioka T, Hirayama T, Nagasawa H, Yamashita Y, Toyokuni S.

Cancer Sci. Vol. 107 ( 3 ) page： 250-257 2016.3

Pain-reducing anesthesia prevents oxidative stress in human term placenta. Reviewed

Tsuzuki Y, Yamashita Y, Hattori Y, Hua Li G, Akatsuka S, Kotani T, Kikkawa F, Naiki-Ito A, Takahashi S, Nishiwaki K, Toyokuni S.

J Clin Biochem Nutr. Vol. 58 ( 2 ) page： 156-60 2016.3

Pain-reducing anesthesia prevents oxidative stress in human term placenta Reviewed International journal

Tsuzuki, Y., Yamashita, Y., Hattori, Y., Li, G.H., Akatsuka, S., Kotani, T., Kikkawa, F., Naiki-Ito, A., Takahashi, S., Nishiwaki, K., Toyokuni, S.

Journal of Clinical Biochemistry and Nutrition Vol. 58 ( 2 ) page： 156 - 60 2016.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SOCIETY FOR FREE RADICAL RESEARCH JAPAN

Anesthesia is sometimes used for the reduction of maternal pain in normal human term labor, but whether the drugs affect oxidative stress remains unclear. The placenta serves as an interface between the maternal and fetal vasculature. In this study, we immunohistochemically analyzed two markers for oxidative stress, namely 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal–modified proteins (HNE), using placentas from 21 cases of normal tansvaginal delivery (V group), 20 Caesarean sections (C group), and 17 normal transvaginal deliveries with epidural anesthesia (E group). 8-OHdG staining in the nuclei of trophoblasts lining the chorionic villi was significantly stronger in the V group either compared with the C or E group (p<0.001), without significant differences in the C and E groups (p = 0.792). Moderate to intense staining by HNE of the intravascular serum of chorionic villi vasculature was frequently observed in the placentas from the V group, but less frequently of those in either C or E groups (p<0.001), nor the p value comparing the C and E groups was significant (p = 0.128) for HNE staining. Our results suggest that although the role of oxidative stress and its influences on fetal state in the placenta in labor remains unclear, it seems to be lessened by epidural anesthesia.

DOI： 10.3164/jcbn.15-138

Role of hemoglobin and transferrin in multi-wall carbon nanotube-induced mesothelial injury and carcinogenesis. Reviewed International journal

Yue Wang, Yasumasa Okazaki, Lei Shi, Hiro Kohda, Minoru Tanaka, Kentaro Taki, Tomoki Nishioka, Tasuku Hirayama, Hideko Nagasawa, Yoriko Yamashita, Shinya Toyokuni

Cancer science Vol. 107 ( 3 ) page： 250 - 7 2016.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Multi-wall carbon nanotubes (MWCNT) are a form of flexible fibrous nanomaterial with high electrical and thermal conductivity. However, 50-nm MWCNT in diameter causes malignant mesothelioma (MM) in rodents and, thus, the International Agency of Research on Cancer has designated them as a possible human carcinogen. Little is known about the molecular mechanism through which MWCNT causes MM. To elucidate the carcinogenic mechanisms of MWCNT in mesothelial cells, we used a variety of lysates to comprehensively identify proteins specifically adsorbed on pristine MWCNT of different diameters (50 nm, NT50; 100 nm, NT100; 150 nm, NT150; and 15 nm/tangled, NTtngl) using mass spectrometry. We identified >400 proteins, which included hemoglobin, histone, transferrin and various proteins associated with oxidative stress, among which we selected hemoglobin and transferrin for coating MWCNT to further evaluate cytotoxicity, wound healing, intracellular catalytic ferrous iron and oxidative stress in rat peritoneal mesothelial cells (RPMC). Cytotoxicity to RPMC was observed with pristine NT50 but not with NTtngl. Coating NT50 with hemoglobin or transferrin significantly aggravated cytotoxicity to RPMC, with an increase in cellular catalytic ferrous iron and DNA damage also observed. Knockdown of transferrin receptor with ferristatin II decreased not only NT50 uptake but also cellular catalytic ferrous iron. Our results suggest that adsorption of hemoglobin and transferrin on the surface of NT50 play a role in causing mesothelial iron overload, contributing to oxidative damage and possibly subsequent carcinogenesis in mesothelial cells. Uptake of NT50 at least partially depends on transferrin receptor 1. Modifications of NT50 surface may decrease this human risk.

DOI： 10.1111/cas.12865

Neuroprotective potential of molecular hydrogen against perinatal brain injury via suppression of activated microglia. Reviewed

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.

Free Radic Biol Med. Vol. 91 page： 154-163 2016.2

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Papers - TOYOKUNI Shinya