研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

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Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion. 査読有り国際誌

Mano Y, Kotani T, Ito M, Nagai T, Ichinohashi Y, Yamada K, Ohno K, Kikkawa F, Toyokuni S

Free radical biology & medicine 69 巻頁： 324 - 30 2014年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Free Radical Biology and Medicine

Molecular hydrogen (H2) scavenges hydroxyl radicals. Recently, H2 has been reported to prevent a variety of diseases associated with oxidative stress in model systems and in humans. Here, we studied the effects of H2 on rat fetal hippocampal damage caused by ischemia and reperfusion (IR) on day 16 of pregnancy with the transient occlusion of the bilateral utero-ovarian arteries. Starting 2 days before the operation, we provided the mothers with hydrogen-saturated water ad libitum until vaginal delivery. We observed a significant increase in the concentration of H 2 in the placenta after the oral administration of hydrogen-saturated water to the mothers, with less placental oxidative damage after IR in the presence of H2. Neonatal growth retardation was observed in the IR group, which was alleviated by the H2 administration. We analyzed the neuronal cell damage in the CA1 and CA3 areas of the hippocampus at day 7 after birth by immunohistochemical analysis of the 8-oxo-7,8-dihydro-2.©2014 ElsevierInc.Allrightsreserved.

DOI： 10.1016/j.freeradbiomed.2014.01.037

Ovarian mucinous tumors arising from mature cystic teratomas-a molecular genetic approach for understanding the cellular origin 査読有り国際誌

Fujii, K; Yamashita, Y; Yamamoto, T; Takahashi, K; Hashimoto, K; Miyata, T; Kawai, K; Kikkawa, F; Toyokuni, S; Nagasaka, T

HUMAN PATHOLOGY 45 巻 ( 4 ) 頁： 717 - 724 2014年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Human Pathology

Mucinous tumors of the ovary are frequently associated with mature cystic teratomas, and it has been speculated that the mucinous tumors arise from teratoma components. The cellular origins of mature cystic teratomas are believed to be post-meiotic ovarian germ cells, and the analysis of microsatellite markers such as short tandem repeats is suitable for determining the cellular origin of tumors. In this study, we analyzed 3 ovarian mature cystic teratomas, all of which were associated with simultaneous ovarian mucinous tumors within the same ovary. Two of the 3 mucinous tumors were intestinal-type and the other was endocervical type. A laser capture microdissection technique was used to separate the epithelial component of the mucinous tumor, the components of the mature cystic teratoma, and control ovarian somatic tissue. Using short tandem repeat analysis based on 6 markers (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290), we could distinguish the germ cell (homozygous) or somatic (heterozygous) origin of a given component in each sample. The epithelial components of the intestinal-type mucinous tumors in cases 1 and 2 were homozygous, and the epithelial component in case 3 (endocervical type) was heterozygous. All teratomatous components were homozygous, and the control components were heterozygous. In addition, we analyzed 3 mature cystic teratomas without mucinous tumors, and all 3 were homozygous in the tumor component. Our data suggest that the origin of mucinous tumors in the ovary may differ among histological subtypes, and intestinal-type mucinous tumors may arise from mature cystic teratomas, although endocervical-type mucinous tumors may not. © 2014 Elsevier Inc.

DOI： 10.1016/j.humpath.2013.10.031

From Nagoya to the world 査読有り国際誌

Toyokuni S.

Nagoya Journal of Medical Science 76 巻 ( 1-2 ) 頁： 1 - 2 2014年3月

From Nagoya to the world 国際誌

Toyokuni S

Nagoya Journal of Medical Science 76 巻 ( 1-2 ) 頁： 1 - 2 2014年3月

RAT MODEL DEMONSTRATES A HIGH RISK OF TREMOLITE BUT A LOW RISK OF ANTHOPHYLLITE FOR MESOTHELIAL CARCINOGENESIS 査読有り

Dilinuer Aierken, Yasumasa Okazaki, Shan Hwu Chew, Akihiro Sakai, Yue Wang, Hirotaka Nagai, Nobuaki Misawa, Norihiko Kohyama, Shinya Toyokuni

NAGOYA JOURNAL OF MEDICAL SCIENCE 76 巻 ( 1-2 ) 頁： 149 - 160 2014年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NAGOYA UNIV, SCH MED

Asbestos was abundantly used in industry during the last century. Currently, asbestos confers a heavy social burden due to an increasing number of patients with malignant mesothelioma ( MM), which develops after a long incubation period. Many studies have been conducted on the effects of the asbestos types that were most commonly used for commercial applications. However, there are few studies describing the effects of the less common types, or minor asbestos. We performed a rat carcinogenesis study using Japanese tremolite and Afghan anthophyllite. Whereas more than 50% of tremolite fibers had a diameter of < 500 nm, only a small fraction of anthophyllite fibers had a diameter of < 500 nm. We intraperitoneally injected 1 or 10 mg of asbestos into F1 Fischer-344/Brown-Norway rats. In half of the animals, repeated intraperitoneal injections of nitrilotriacetate (NTA), an iron chelator to promote Fenton reaction, were performed to evaluate the potential involvement of iron overload. Tremolite induced MM with a high incidence (96% with 10 mg; 52% with 1 mg), and males were more susceptible than females. Histology was confirmed using immunohistochemistry, and most MMs were characterized as the sarcomatoid or biphasic subtype. Unexpectedly NTA showed an inhibitory effect in females. In contrast, anthophyllite induced no MM after an observation period of 550 days. The results suggest that the carcinogenicity of anthophyllite is weaker than formerly reported, whereas that of tremolite is as potent as major asbestos as compared with our previous data.

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Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis.

Aierken D, Okazaki Y, Chew SH, Sakai A, Wang Y, Nagai H, Misawa N, Kohyama N, Toyokuni S

Nagoya journal of medical science 76 巻 ( 1-2 ) 頁： 149 - 60 2014年2月

Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis.

Aierken D, Okazaki Y, Chew SH, Sakai A, Wang Y, Nagai H, Misawa N, Kohyama N, Toyokuni S

Nagoya journal of medical science 76 巻 ( 1-2 ) 頁： 149 - 60 2014年2月

RAT MODEL DEMONSTRATES A HIGH RISK OF TREMOLITE BUT A LOW RISK OF ANTHOPHYLLITE FOR MESOTHELIAL CARCINOGENESIS

Aierken Dilinuer, Okazaki Yasumasa, Chew Shan Hwu, Sakai Akihiro, Wang Yue, Nagai Hirotaka, Misawa Nobuaki, Kohyama Norihiko, Toyokuni Shinya

NAGOYA JOURNAL OF MEDICAL SCIENCE 76 巻 ( 1-2 ) 頁： 149 - 160 2014年2月

Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis. 査読有り国際誌

Aierken D., Okazaki Y., Chew S.H., Sakai A., Wang Y., Nagai H., Misawa N., Kohyama N., Toyokuni S.

Nagoya journal of medical science 76 巻 ( 1-2 ) 頁： 149 - 160 2014年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nagoya journal of medical science

Asbestos was abundantly used in industry during the last century. Currently, asbestos confers a heavy social burden due to an increasing number of patients with malignant mesothelioma (MM), which develops after a long incubation period. Many studies have been conducted on the effects of the asbestos types that were most commonly used for commercial applications. However, there are few studies describing the effects of the less common types, or minor asbestos. We performed a rat carcinogenesis study using Japanese tremolite and Afghan anthophyllite. Whereas more than 50% of tremolite fibers had a diameter of < 500 nm, only a small fraction of anthophyllite fibers had a diameter of < 500 nm. We intraperitoneally injected 1 or 10 mg of asbestos into F1 Fischer-344/Brown-Norway rats. In half of the animals, repeated intraperitoneal injections of nitrilotriacetate (NTA), an iron chelator to promote Fenton reaction, were performed to evaluate the potential involvement of iron overload. Tremolite induced MM with a high incidence (96% with 10 mg; 52% with 1 mg), and males were more susceptible than females. Histology was confirmed using immunohistochemistry, and most MMs were characterized as the sarcomatoid or biphasic subtype. Unexpectedly NTA showed an inhibitory effect in females. In contrast, anthophyllite induced no MM after an observation period of 550 days. The results suggest that the carcinogenicity of anthophyllite is weaker than formerly reported, whereas that of tremolite is as potent as major asbestos as compared with our previous data.

Scopus

Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production. 査読有り国際誌

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

Carcinogenesis 35 巻 ( 1 ) 頁： 164 - 72 2014年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Carcinogenesis

Like many other human cancers, the development of malignant mesothelioma is closely associated with a chronic inflammatory condition. Both macrophages and mesothelial cells play crucial roles in the inflammatory response caused by asbestos exposure. Here, we show that adipocytes can also contribute to asbestos-induced inflammation through dysregulated adipocytokine production. 3T3-L1 preadipocytes were differentiated into mature adipocytes prior to use. These cells took up asbestos fibers (chrysotile, crocidolite and amosite) but were more resistant to asbestos-induced injury than macrophages and mesothelial cells. Expression microarray analysis followed by reverse transcription-PCR revealed that adipocytes respond directly to asbestos exposure with an increased production of proinflammatory adipocytokines [e.g. monocyte chemoattractant protein-1 (MCP-1)], whereas the production of anti-inflammatory adipocytokines (e.g. adiponectin) is suppressed. This was confirmed in epididymal fat pad of mice after intraperitoneal injection of asbestos fibers. Such dysregulated adipocytokine production favors the establishment of a proinflammatory environment. Furthermore, MCP-1 marginally promoted the growth of MeT-5A mesothelial cells and significantly enhanced the wound healing of Y-MESO-8A and Y-MESO-8D human mesothelioma cells. Our results suggest that increased levels of adipocytokines, such as MCP-1, can potentially contribute to the promotion of mesothelial carcinogenesis through the enhanced recruitment of inflammatory cells as well as a direct growth and migration stimulatory effect on mesothelial and mesothelioma cells. Taken together, our findings support a potential cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis. © The Author 2013. Published by Oxford University Press. All rights reserved.

DOI： 10.1093/carcin/bgt267

Iron overload as a major targetable pathogenesis of asbestos-induced mesothelial carcinogenesis 査読有り国際誌 Open Access

Toyokuni, S

REDOX REPORT 19 巻 ( 1 ) 頁： 1 - 7 2014年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Redox Report

Few people expected that asbestos, a fibrous mineral, would be carcinogenic to humans. In fact, asbestos is a definite carcinogen in humans, causing a rare but aggressive cancer called malignant mesothelioma (MM). Mesothelial cells line the three somatic cavities and thus do not face the outer surface, but reduce the friction among numerous moving organs. MM has several characteristics: extremely long incubation period of 30-40 years after asbestos exposure, difficulty in clinical diagnosis at an early stage, and poor prognosis even under the current multimodal therapies. In Japan, 'Kubota shock' attracted considerable social attention in 2005 for asbestos-induced mesothelioma and, thereafter, the government enacted a law to provide the people suffering from MM a financial allowance. Several lines of recent evidence suggest that the major pathology associated with asbestos-induced MM is local iron overload, associated with asbestos exposure. Preclinical studies to prevent MM after asbestos exposure with iron reduction are in progress. In addition, novel target genes in mesothelial carcinogenesis have been discovered with recently recognized mesothelioma-prone families. Development of an effective preventive strategy is eagerly anticipated because of the long incubation period for MM. © W. S. Maney & Son Ltd 2014.

DOI： 10.1179/1351000213Y.0000000075

As a host society to SFRRI 2014 in Kyoto. Open Access

Handa O, Naito Y, Toyokuni S

Journal of clinical biochemistry and nutrition 54 巻 ( 1 ) 頁： 1 - 1 2014年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Clinical Biochemistry and Nutrition

It is our great honor to host the 17th Biennial Meeting of Society for Free Radical Research International (SFRRI 2014) that is being held at the Kyoto International Conference Center, in Kyoto, Japan on March 23rd–26th, 2014. Previously we had this biennial meeting twice in Kyoto, in the year 1988 and 2000. This meeting has a great meaning not only for every member in SFRRI but also for those in SFRR Japan, since the SFRRI 1998 meeting was a key event behind the establishment of SFRR Japan. Since 1998, SFRR Japan has expanded the number of the members and has developed a variety of original research activities. The International Scientific Program Committee (ISPC) representing each region of SFRR has worked hard all together to develop what we believe will be an exciting and informative meeting to both young and senior participants. As a result, the congress will include award lectures and symposia on novel aspects of free radical research, which was democratically selected after the application during December 2012 and January 2013 by the voting of ISPC. Concurrent symposia will address in-depth and cutting-edge scientific topics in free radical chemistry, biology and medicine. In addition, the meeting will have four plenary lectures presented by Prof. Rafael Radi (Uruguay), Prof. Harold. M Swartz (USA), Prof. Arturo Zychlinsky (Germany) and Prof. Hideyuki Saya (Japan). Each lecture would reveal novel aspects of free radical research. It has been our sincere wish to make the meeting affordable and attractive especially to young scientists. There will be several awards from each region of SFRR as well as from this meeting. Sunrise lecture for the beginner of free radical research will be presented. Several satellite meetings are now planned in order to allow participants with special interests to meet. The congress venue, Kyoto city, is a UNESCO World Heritage site with a long and rich history going back over 1,200 years and was the original imperial capital of Japan. With more than 3,000 temples and shrines, full of traditional Japanese culture, with cherry blossoms presumably in full bloom, Kyoto city will deeply inspire your sixth sense. Besides traditional atmosphere, Kyoto city is thriving and exciting modern city with excellent facilities and easy links to the rest of the world. We believe that SFRRI 2014 meeting will be rich in science, and a great opportunity to hear cutting edge advances in the free radical research, as well as an opportunity to renew old friendships and establish new collaborations and associations. We look forward to meeting all of you in Kyoto in March 2014.

DOI： 10.3164/jcbn.54-1E1

Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production. 査読有り

Chew SH, Okazaki Y, Nagai H, Misawa N, Akatsuka S, Yamashita K, Jiang L, Noguchi M, Hosoda K, Sekido Y, Takahashi T and Toyokuni S.

Carcinogenesis 35 巻頁： 164-172 2014年

Preclinical evaluation of an O(6)-methylguanine-DNA methyltransferase-siRNA/liposome complex administered by convection-enhanced delivery to rat and porcine brains. 査読有り

Tsujiuchi T, Natsume A, Motomura K, Kondo G, Ranjit M, Hachisu R, Sugimura I, Tomita S, Takehara I, Woolley M, Barua NU, Gill SS, Bienemann AS, Yamashita Y, Toyokuni S, Wakabayashi T.

Am J Transl Res 15 巻頁： 169-178 2014年

Dexamethasone palmitate ameliorates macrophages-1 rich graft-versus-host disease by inhibiting macrophage functions. 査読有り

Nishiwaki S, Nakayama T, Murata M, Nishida T, Terakura S, Saito S, Kato T. Mizuno H, Imahashi N, Seto S, Ozawa Y, Miyamura K, Ito M, Takeshita K, Kato H, Toyokuni S, Nagao K, Ueda R and Naoe T.

PLoS ONE 9 巻頁： e96252 2014年

Histological detection of catalytic ferrous iron with the selective turn-on fluorescent probe RhoNox-1 in a Fenton reaction-based rat renal carcinogenesis model. 査読有り

Mukaide T, Hatori Y, Misawa N, Funahashi S, Jiang L, Hirayama T, Nagasawa H and Toyokuni S.

Free Radic Res 48 巻頁： 990-995 2014年

Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis. 査読有り

Aierken D, Okazaki Y, Chew SH, Sakai A, Wang Y, Nagai H, Misawa N, Kohyama N and Toyokuni S.

Nagoya J Med Sci 76 巻頁： 149-160 2014年

Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage by in ut ero ischemia-reperfusion. 査読有り

Mano Y, Kotani T, Ito M, Nagai T, Ichinohashi Y, Yamada K, Ohno K, Kikkawa F and Toyokuni S.

Free Radic Biol Med 69 巻頁： 324-330 2014年

Lack of presence of the human cytomegalovirus in human glioblastoma. Modern Pathol 27: 922-929, 2014. 査読有り

Yamashita Y, Ito Y, Isomura H, Takemura N, Okamoto A, Motomura K, Tsujiuchi T, Natsume A, Wakabayashi T, Toyokuni S and Tsurumi T.

Modern Pathology 27 巻頁： 922-929 2014年

Ovarian mucinous tumors arising from mature cystic teratomas-a molecular genetic approach for understanding the cellular origin. 査読有り

Fujii K, Yamashita Y, Yamamoto T, Takahashi K, Hashimoto K, Miyata T, Kawai K, Kikkawa F, Toyokuni S, Nagasaka T.

Human Pathol 45 巻頁： 717-724 2014年

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