研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

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Improvement in hepatic lipid peroxidation in patients with complete response to interferon-α treatment for chronic hepatitis C. 国際誌

Kageyama, F; Kobayashi, Y; Kawasaki, T; Toyokuni, S; Uchida, K; Nakamura, H

HEPATOLOGY 28 巻 ( 4 ) 頁： 250A - 250A 1998年10月

Role of cytochrome P450 isoforms and free radicals in endotoxemic liver injury.

Minamiyama, Y; Takemura, S; Imaoka, S; Toyokuni, S; Funae, Y; Kinoshita, H; Inoue, M

HEPATOLOGY 28 巻 ( 4 ) 頁： 251A - 251A 1998年10月

Role of cytochrome P450 isoforms and free radicals in endotoxemic liver injury. 査読有り

Minamiyama Y, Takemura S, Imaoka S, Toyokuni S, Funae Y, Kinoshita H, Inoue M

HEPATOLOGY 28 巻 ( 4 ) 頁： 251A - 251A 1998年10月

Improvement in hepatic lipid peroxidation in patients with complete response to interferon-alpha treatment for chronic hepatitis C. 査読有り国際誌

Kageyama F, Kobayashi Y, Kawasaki T, Toyokuni S, Uchida K, Nakamura H

HEPATOLOGY 28 巻 ( 4 ) 頁： 250A - 250A 1998年10月

Improvement in hepatic lipid peroxidation in patients with complete response to interferon-α treatment for chronic hepatitis C. 国際誌

Kageyama, F, Kobayashi, Y, Kawasaki, T, Toyokuni, S, Uchida, K, Nakamura, H

HEPATOLOGY 28 巻 ( 4 ) 頁： 250A - 250A 1998年10月

Heat shock preconditioning ameliorates liver injury following normothermic ischemia-reperfusion in steatotic rat livers

Yamagami K, Yamamoto Y, Kume M, Kimoto S, Yamamoto H, Ozaki N, Yamamoto M, Shimahara Y, Toyokuni S, Yamaoka Y

JOURNAL OF SURGICAL RESEARCH 79 巻 ( 1 ) 頁： 47 - 53 1998年9月

Heat shock preconditioning ameliorates liver injury following normothermic ischemia-Reperfusion in steatotic rat livers

Yamagami K., Yamamoto Y., Kume M., Kimoto S., Yamamoto H., Ozaki N., Yamamoto M., Shimahara Y., Toyokuni S., Yamaoka Y.

Journal of Surgical Research 79 巻 ( 1 ) 頁： 47 - 53 1998年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Surgical Research

The decreased tolerance of steatotic livers to warm ischemia complicates liver surgery. The efficacy of heat shock preconditioning in steatotic livers to lessen ischemia-reperfusion injury was studied in rats. Steatotic liver was produced in Lewis rats with a choline-deficient diet. Rats with steatotic livers were divided into a heat shock preconditioned group (group HS) and a control group (group C). All rats received 45 min of hepatic warm ischemia. Survival rates and changes in biochemical and histological parameters were compared in both groups. Heat shock protein 72 (HSP72) was produced only in group HS. The 7-day survival of the rats after warm ischemic intervention was significantly better in group HS (13/15) than in group C (5/15) (P < 0.01). The concentration of ATP in liver tissue (n = 10, P < 0.01) and serum levels of aspartate aminotransferase (n = 10, P < 0.05), alanine aminotransferase (n = 10, P < 0.01), and lactic dehydrogenase (n = 10, P < 0.01) at 40 min reperfusion were also significantly better in group HS than in group C. Histological examination at 40 min reperfusion showed severe sinusoidal congestion, hepatocyte necrosis, and increased positivity to 4-hydroxy-2- nonenal-modified proteins in group C livers; these signs were markedly suppressed in group HS livers. The data indicate that heat shock preconditioning provides the steatotic rat liver with significant tolerance to warm ischemia-reperfusion injury.

DOI： 10.1006/jsre.1998.5403

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Development of High-grade Renal Cell Carcinomas in Rats Independently of Somatic Mutations in the Tsc2 and VHL Tumor Suppressor Genes

TOYOKUNI Shinya, OKADA Kunihiko, KONDO Shohei, NISHIOKA Hiroaki, TANAKA Tomoyuki, NISHIYAMA Yasuyuki, HINO Okio, HIAI Hiroshi

Japanese journal of cancer research : gann 89 巻 ( 8 ) 頁： 814 - 820 1998年8月

Development of High-grade Renal Cell Carcinomas in Rats Independently of Somatic Mutations in the Tsc2 and VHL Tumor Suppressor Genes 国際誌

TOYOKUNI Shinya, OKADA Kunihiko, KONDO Shohei, NISHIOKA Hiroaki, TANAKA Tomoyuki, NISHIYAMA Yasuyuki, HINO Okio, HIAI Hiroshi

Japanese journal of cancer research : gann 89 巻 ( 8 ) 頁： 814 - 820 1998年8月

Development of high-grade renal cell carcinomas in rats independently of somatic mutations in the Tsc2 and VHL tumor suppressor genes

Toyokuni S, Okada K, Kondo S, Nishioka H, Tanaka T, Nishiyama Y, Hino O, Hiai H

JAPANESE JOURNAL OF CANCER RESEARCH 89 巻 ( 8 ) 頁： 814 - 820 1998年8月

A processed grain food inhibits hepatic injury in endotoxemic rats

Minamiyama Y, Takemura S, Toyokuni S, Tanimoto Y, Sato EF, Inoue M

JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY 44 巻 ( 4 ) 頁： 547 - 559 1998年8月

Development of high-grade renal cell carcinomas in rats independently of somatic mutations in the Tsc2 and VHL tumor suppressor genes

Toyokuni S., Okada K., Kondo S., Nishioka H., Tanaka T., Nishiyama Y., Hino O., Hiai H.

Japanese Journal of Cancer Research 89 巻 ( 8 ) 頁： 814 - 820 1998年8月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Cancer Research

Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular damage that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. The RCCs are characterized by 1) high incidence of pulmonary metastasis and peritoneal invasion, 2) high incidence of tumor-associated mortality and 3) possible involvement of reactive oxygen species in carcinogenesis. The present study investigated the possible role of Tsc2 and VHL tumor suppressor genes in this model. Thirty-four Fe-NTA-induced primary RCCs and 20 other primary or metastatic tumors of rats were searched for genetic alteration in all the coding exons of both genes by polymerase chain reaction-single-strand-conformation polymorphism analysis and sequencing in conjunction with morphological evaluation. In the Fe-NTA-induced RCCs, frequency of metastasis or invasion was proportionally associated with the nuclear grade of the tumor (grades 1-3). Only one Fe-NTA-induced RCC of grade 1 revealed missense mutations with loss of heterozygosity in exon 10 of the Tsc2 gene (codons 334, GTG (Val) to GCG (Ala), and 336, TAT (Tyr) to CAT (His)). No mutation was found in the VHL gene. The results suggest that 1) high-grade RCCs can develop in the absence of mutations in the Tsc2 and VHL genes in rats, and that 2) Tsc2 gene somatic mutation can nonetheless be one of the causes of non-Eker rat RCCs.

DOI： 10.1111/j.1349-7006.1998.tb00633.x

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Development of high-grade renal cell carcinomas in rats independently of somatic mutations in the Tsc2 and VHL tumor suppressor genes

Toyokuni S, Okada K, Kondo S, Nishioka H, Tanaka T, Nishiyama Y, Hino O, Hiai H

JAPANESE JOURNAL OF CANCER RESEARCH 89 巻 ( 8 ) 頁： 814 - 820 1998年8月

Oxidative stress and cancer: The role of redox regulation

Toyokuni S.

Biotherapy 11 巻 ( 2-3 ) 頁： 147 - 154 1998年7月

Over-expression of glutathione S-transferase Yp isozyme and concomitant down-regulation of Ya isozyme in renal cell carcinoma of rats induced by ferric nitrilotriacetate 査読有り国際誌

Tanaka T, Nishiyama Y, Okada K, Satoh K, Fukuda A, Uchida K, Osawa T, Hiai H, Toyokuni S

CARCINOGENESIS 19 巻 ( 5 ) 頁： 897 - 903 1998年5月

Oxidative stress in pancreatic β-cells of GK rat, a model of non-obese NIDDM

Ihara, Y; Yamada, Y; Uchida, K; Toyokuni, S; Seino, Y

DIABETES 47 巻頁： A263 - A263 1998年5月

Oxidative stress in pancreatic beta-cells of GK rat, a model of non-obese NIDDM 国際誌

Ihara Y, Yamada Y, Uchida K, Toyokuni S, Seino Y

DIABETES 47 巻頁： A263 - A263 1998年5月

Over-expression of glutathione S-transferase Yp isozyme and concomitant down-regulation of Ya isozyme in renal cell carcinoma of rats induced by ferric nitrilotriacetate

Tanaka T., Nishiyama Y., Okada K., Satoh K., Fukuda A., Uchida K., Osawa T., Hiai H., Toyokuni S.

Carcinogenesis 19 巻 ( 5 ) 頁： 897 - 903 1998年5月

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

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal tubular damage, a consequence of iron-catalysed Fenton-like reactions, that finally leads to a high incidence of renal cell carcinoma (RCC) in rodents. Glutathione S-transferase (GST) is a family of enzymes that play an important role in detoxification of hydrophobic and electrophilic molecules, and has been associated with putative preneoplastic foci of rat hepatocarcinogenesis and chemotherapy-resistance of human cancers. Our previous study revealed an induction of π-class glutathione S-transferase (Yp) mRNA in the kidney 3 h after administration of Fe-NTA. In the present study, expression of GST isozymes were further investigated in the Fe-NTA-induced RCCs of rats which are characterized by (1) high incidence of metastasis and invasion, (2) high incidence of tumour-associated mortality, and (3) possible involvement of reactive oxygen species in carcinogenesis. In the Fe-NTA-induced RCCs, the levels of α-class GST (Ya) mRNA and proteins were markedly decreased with no apparent change in the copy number of the gene. In contrast, GST-Yp mRNA and proteins were significantly increased in the RCCs while the total GST enzymatic activity was decreased. Immunohistochemical analysis revealed intense staining of GST-Yp not only in the primary RCCs and its metastatic sites, but also in their non-tumorous part of proximal tubules. The contrastive expression of GST isozymes in this renal carcinogenesis model suggests an alteration of its transcription mechanisms and warrants further investigation of this particular detoxifying enzyme from the viewpoint of reactive oxygen species-induced carcinogenesis.

DOI： 10.1093/carcin/19.5.897

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Immunohistochemical detection of 4-hydroxy-2-nonenal-modified-protein adducts in human alcoholic liver diseases

Ohhira M, Ohtake T, Matsumoto A, Saito H, Ikuta K, Fujimoto Y, Ono M, Toyokuni S, Kohgo Y

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 22 巻 ( 3 ) 頁： 145S - 149S 1998年5月

Immunohistochemical detection of 4-hydroxy-2-nonenal-modified-protein adducts in human alcoholic liver diseases 査読有り

M Ohhira, T Ohtake, A Matsumoto, H Saito, K Ikuta, Y Fujimoto, M Ono, S Toyokuni, Y Kohgo

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 22 巻 ( 3 ) 頁： 145S - 149S 1998年5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：LIPPINCOTT WILLIAMS & WILKINS

4-Hydroxy-2-nonenal (HNE) is one of the major components of lipid peroxidation product and has been shown to react with proteins to form HNE-protein adducts. HNE-protein adducts are relatively stable and can be used as a marker of radical-mediated cellular damage. We report herein the immunohistochemical analysis of HNE-protein adducts in human alcoholic liver diseases using a specific monoclonal antibody HNEJ-2. Cytoplasm of hepatocytes and bile duct epithelia was positively stained for HNE-protein adducts, and the nucleus was negligibly stained. The immunohistochemical intensity of hepatocytes was classified into three groups: strong, moderate, and faint staining. Strong staining was found in 43% of alcoholic liver diseases and in 4% of viral liver diseases. Hepatocytes of alcoholic liver diseases contained a higher amount of HNE-protein adducts than those of viral liver diseases, and the difference was statistically significant (p = 0.005; chi(2) test). Semiquantitative analysis of the histological intensities of HNE-protein adducts and iron indicated a significant positive correlation (p = 0.084; Spearman's rank correlation). The localization of HNE-protein adducts and iron in hepatocytes appeared to be identical. These data suggested the correlation between HNE-protein adducts and iron. Our results indicate that HNE-protein adducts, a marker of oxidative stress-induced damage, are increased in human alcoholic liver damage, and that hepatic siderosis may act on the production of free radicals.

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