Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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A Novel Method for Efficient Collection of Normal Mesothelial Cells In Vivo Reviewed

Li Jiang, Yoriko Yamashita, Shinya Toyokuni

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION Vol. 46 ( 3 ) page： 265 - 268 2010.5

Language：English Publishing type：Research paper (scientific journal) Publisher：JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION

Asbestos-induced mesothelioma is a challenging social problem in many countries, and oxidative stress via iron is closely associated with its carcinogenesis. Mesothelioma is thought to originate from the mesothelial cells that cover the somatic cavity such as pleural, pericardial and peritoneal cavities. They are single layered and so flat that it is extremely difficult to obtain pure mesothelial cells as control samples from experimental animals. Here we describe a novel method to collect mesothelial cells from animals by the use of simple equipments. Surface of the most organs including lung, spleen and liver are covered with a single layer of mesothelial cells. Scraping the surface of those organs with razor blades after snap-freeze in liquid nitrogen satisfactorily confers almost pure population of mesothelial cells. This simple method would be helpful for obtaining mesothelial control samples from animals to elucidate the molecular mechanisms of a variety of mesothelial pathology.

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A Novel Method for Efficient Collection of Normal Mesothelial Cells In Vivo

Jiang Li, Yamashita Yoriko, Toyokuni Shinya

Journal of Clinical Biochemistry and Nutrition Vol. 46 ( 3 ) page： 265 - 268 2010.5

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

DOI： 10.3164/jcbn.10-01

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CiNii Research

リンパ腫ゲノムにおけるマイクロサテライト多型不安定性集積の空間統計学解析

鶴山竜昭, リチャード・カシンスキー, 赤塚慎也, 今井裕紀子, 竹内晴哉, 尾関宗孝, 奥野知子, 豊國伸哉, 玉木敬二

日本法医学雑誌 Vol. 64 ( 1 ) page： 54 - 54 2010.5

n-3 polyunsaturated fatty acids promote apoptosis in oxidatively stressed transgenic mouse models International journal

Fan, YY; Toyokuni, S; Callaway, ES; Ran, Q; Lupton, JR; Chapkin, RS

CANCER RESEARCH Vol. 70 2010.4

A Quantitative trait locus responsible for inducing B-cell lymphoblastic lymphoma is a hotspot for microsatellite instability

KASZYNSKI Richard H., AKATSUKA Shinya, HIRATSUKA Takuya, JIN Guang, OZEKI Munetaka, OKUNO Tomoko, NAKAMURA Takuro, MANABE Toshiaki, TAKAKUWA Tetsuya, HIAI Hiroshi, TOYOKUNI Shinya, TAMAKI Keiji, TSURUYAMA Tatsuaki

Vol. 101 ( 3 ) page： 800 - 805 2010.3

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma. Reviewed International journal Open Access

Qian Hu, Shinya Akatsuka, Yoriko Yamashita, Hiroki Ohara, Hirotaka Nagai, Yasumasa Okazaki, Takashi Takahashi, Shinya Toyokuni

Laboratory investigation; a journal of technical methods and pathology Vol. 90 ( 3 ) page： 360 - 73 2010.3

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

In humans, mesothelioma has been linked to asbestos exposure, especially crocidolite and amosite asbestos, which contain high amounts of iron. Previously, we established a rat model of iron-induced peritoneal mesothelioma with repeated intraperitoneal injections of iron saccharate and an iron chelator, nitrilotriacetate. Here, we analyze these mesotheliomas using array-based comparative genomic hybridization (aCGH) and gene expression profiling by micro-array. Mesotheliomas were classified into two distinct types after pathologic evaluation by immunohistochemistry. The major type, epithelioid mesothelioma (EM), originated in the vicinity of tunica vaginalis testis, expanded into the upper peritoneal cavity and exhibited papillary growth and intense podoplanin immunopositivity. The minor type, sarcomatoid mesothelioma (SM), originated from intraperitoneal organs and exhibited prominent invasiveness and lethality. Both mesothelioma types showed male preponderance. SMs revealed massive genomic alterations after aCGH analysis, including homozygous deletion of CDKN2A/2B and amplification of ERBB2 containing region, whereas EMs showed less genomic alterations. Uromodulin was highly expressed in most of the cases. After 4-week treatment, iron deposition in the mesothelia was observed with 8-hydroxy-2'-deoxyguanosine formation. These results not only show two distinct molecular pathways for iron-induced peritoneal mesothelioma, but also support the hypothesis that oxidative stress by iron overload is a major cause of CDKN2A/2B homozygous deletion.

DOI： 10.1038/labinvest.2009.140

A Quantitative trait locus responsible for inducing B-cell lymphoblastic lymphoma is a hotspot for microsatellite instability Reviewed International coauthorship International journal Open Access

Richard H. Kaszynski, Shinya Akatsuka, Takuya Hiratsuka, Guang Jin, Munetaka Ozeki, Tomoko Okuno, Takuro Nakamura, Toshiaki Manabe, Tetsuya Takakuwa, Hiroshi Hiai, Shinya Toyokuni, Keiji Tamaki, Tatsuaki Tsuruyama

CANCER SCIENCE Vol. 101 ( 3 ) page： 800 - 5 2010.3

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

While the molecular mechanisms underlying microsatellite instability (MSI) have been exhaustively investigated, identifying the patterns of MSI distribution within diverse cancer genomes has remained an elusive issue. In the present study, we conducted genome-wide MSI screening in B-cell lymphoblastic lymphomas (B-LBL) which spontaneously develop in the SL/Kh strain of mice. Tumor samples harvested from 16 mice were investigated using a framework map consisting of 150 microsatellite markers spaced at increments of roughly 0.5-3.0 centimorgans, spanning the entirety of mouse chromosomes (mus musculus chromosomes [MMU]) 3-6. MMU3 contains a quantitative trait locus (QTL), Bomb1 (bone marrow pre-B1), known to induce an aberrant expansion of pre-B cells in bone marrow prior to the onset of B-LBL in SL/Kh mice. The remaining chromosomes were selected on the basis of those most closely resembling MMU3 in terms of total estimated length (maximum variance 10 Mb). MSI was confirmed at 2 <= markers in DNA derived from tumor tissues in 15 SL/Kh mice (93.7%), while healthy splenic DNA samples screened in parallel were consistently negative for MSI. The overall MSI incidence was significantly higher on MMU3 compared with MMU4-6 (P = 0.031). Additionally, by applying spatial point pattern analysis combined with a 1-D version of Ripley's K-function, we successfully demonstrated the predilection of MSI-susceptible loci to structure a massive cluster within the Bomb1 locus. Our study is the first to suggest that a QTL concomitantly serves as a hotspot for MSI-susceptible loci and sheds new light on somatic cancer genetics. (Cancer Sci 2010; 101: 800-805)

DOI： 10.1111/j.1349-7006.2009.01437.x

前駆B芽球性リンパ腫におけるマイクロサテライト不安定性解析とポイントパターン解析の応用

鶴山竜昭, リチャード・カシンスキー, 赤塚慎也, 中村卓郎, 真鍋敏明, 日合弘, 玉木敬二, 豊國伸哉

日本病理学会会誌 Vol. 99 ( 1 ) page： 217 - 217 2010.3

From the Special Session of the "Special Coordination Funds for Promoting Science and Technology (H18-13-3-1)" Entitled "Malignant Mesothelioma" in the 55^<th> Annual Meeting of the Japanese Society of Occupational Medicine and Traumatology : Brief Overview and Approaches from the Basic Science

OTSUKI Takemi, NAKANO Takashi, HASEGAWA Seiki, OKADA Morihito, TSUJIMURA Tohru, SEKIDO Yoshitaka, TOYOKUNI Shinya, NISHIMOTO Hiroshi, FUKUOKA Kazuya, TANAKA Fumihiro

Japanese journal of occupational medicine and traumatology Vol. 58 ( 1 ) page： 1 - 8 2010.1

*Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma. Reviewed

Hu Q, Akatsuka S, Yamashita Y, Ohara H, Nagai H, Okazaki Y, Takahashi T, Toyokuni S.

Lab. Invest. Vol. 90 page： 360-372 2010.1

Stage-specific roles of fibulin-5 during oxidative stress-induced renal carcinogenesis in rats. Reviewed

Ohara H, Akatsuka S, Nagai H, Liu YT, Jiang L, Okazaki Y, Yamashita Y, Nakamura T and Toyokuni S.

Free Radic Res page： (in press) 2010

A quantitative trait locus for inducing B-cell lymphoblastic lymphoma is a hot spot for microsatellite instability. Reviewed

Kaszynski RH, Akatsuka S, Hiratsuka T, Jin G, Ozeki M, Okuno T, Nakamura T, Manabe T, Takakuwa T, Hiai H, Toyokuni S, Tamaki K and Tsuruyama T.

Cancer Sci Vol. 101 page： 800-805 2010

CD8+CD122+ Regulatory T Cells and CD4+ Treg Cooperatively Prevent and Cure CD4+ cell-induced Colitis. Reviewed

Endharti AT, Okuno Y, Shi Z, Misawa N, Toyokuni S, Ito M, Isobe KI and Suzuki H.

Vol. 186 page： 41-52 2010

Toward a new era of the Nagoya Journal of Medical Science: message from the new editor-in-chief. Invited

Toyokuni S.

Nagoy J Med Sci Vol. 72 page： 107-109 2010

A beverage containing fermented black soybean ameliorates ferric nitrilotriacetate-induced renal oxidative damage in rats. Reviewed

Okazaki Y, Iqbal M, Kawakami N, Yamamoto Y, Toyokuni S and Okada S.

J Clin Biochem Nutr Vol. 47 page： 198-207 2010

Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials. Reviewed

Nagai H and Toyokuni S.

Arch Biochem Biophys Vol. 502 page： 1-7 2010

Genome-scale approaches to investigate oxidative DNA damage. Reviewed

Akatsuka S and Toyokuni S.

J Clin Biochem Nutr Vol. 47 page： 91-97 2010

Lipid peroxidation generates a body odor component trans-2-nonenal covalently bound to protein in vivo. Reviewed

Ishino K, Wakita C, Shibata T, Toyokuni S, Machida S, Matsuda S, Matsuda T and Uchida K.

J Biol Chem Vol. 285 page： 15302-15313 2010

Suppression of SLC11A2 expression is essential to maintain duodenal integrity during dietary iron overload. Reviewed

Shirase T, Mori K, Okazaki Y, Itoh K, Yamamoto M, Tabuchi M, Kishi F, Jiang L, Akatsuka S, Nakao K and Toyokuni S.

Am J Pathol Vol. 177 page： 677-685 2010

Novel method for efficient collection of normal mesothelial cells in vivo. Reviewed

Jiang L, Yamashita Y and Toyokuni S.

J Clin Biochem Nutr Vol. 46 page： 265-268 2010

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