Updated on 2024/04/10

写真a

 
KAKEHASHI Anna
 
Organization
Graduate School of Medicine Department of Basic Medical Science Associate Professor
School of Medicine Department of Medical Science
Title
Associate Professor
Affiliation
Institute of Medicine
Other name(s)
KINOSHITA ANNA
Profile
Anna Kakehashi had entered Osaka City University Graduated School of Medicine in April, 1999 and graduated with PhD Degree in March, 2003. Thereafter, she was employed at the Department of Molecular Pathology, Osaka City University Graduate School of Medicine as a Research Resident, in 2007 became the Research Associate, and in 2013 Lecturer at the same Department. The research theme is related to Experimental Pathology, Molecular Pathology and Chemical Carcinogenesis, mostly devoted to the mechanisms of carcinogenesis, cancer risk assessment, early detection, prevention, and treatment of cancer. Recently, her research is focused on hepatocellular carcinoma, with regard to hepatocarcinogenesis, and elucidation of new cancer and cancer stem cell markers related to human hepatitis virus and non-alcoholic steatohepatitis (NASH) using a wide range of methods. In respect with internation research, her work on the risk assessment of Bioethanol (ETBE) was highly evaluated by Environmetal Protection Agency (US EPA). Furthermore, from 2020 with Chiang Mai University, School of Medicine, Thailand. Osaka Metropolitan University has received an agreement exchange subsidy project (researcher dispatch) with overseas universities.
Affiliation campus
Abeno Campus

Position

  • Graduate School of Medicine Department of Basic Medical Science 

    Associate Professor  2023.07 - Now

  • Graduate School of Medicine Department of Basic Medical Science 

    Lecturer  2013.04 - 2023.06

  • School of Medicine Department of Medical Science 

    Assistant Professor  2006.07 - 2013.03

  • School of Medicine Department of Medical Science  Japan Society for the Promotion of Science

    Research Fellow  2006.04 - 2006.06

  • School of Medicine Department of Medical Science  Ministry of Health, Labor and Welfare Subsidy Young Researcher Development and Utilization Project

    Research resident  2003.12 - 2006.03

Degree

  • Doctor of Medical Science ( Osaka City University )

  • Master of Science ( Others ) (   Saint-Petersburg State University )

Research Areas

  • Life Science / Experimental pathology  / Chemical carcinogenesis, molecular pathology, NASH, oxidative stress-DNA damage-DNA repair

Research Interests

  • Cancer biomarkers and molecular targets

  • Oxidative stress-DNA damage-DNA repair

  • Cancer Prevention

  • MAFLD/MASH

  • Cancer Risk Assessment

  • Molecular Pathology

  • Chemical Carcinogenesis

  • Translational Research

  • Hepatocellular carcinoma

  • PDAC

Research subject summary

  • Investigation of mechanisms of carcinogenesis: biochemical and molecular-biological analyses.
    Investigation of biomarkers and mechanisms of virus and NASH-associated liver cancer, and invasive pancreatic ductal carcinoma.
    Analysis of the proteome, metabolome alterations and biological markers in carcinogenesis.
    Oxidative stress, DNA damage and repair in carcinogenesis.
    Risk assessment of chemical carcinogens.
    Cancer Prevention.

Research Career

  • 浸潤性膵管がんの早期発見バイオ―マーカー及び発がん機序解明

    2020.04 - Now 

  • Analysis of mechanisms of NASH-associated carcinogenesis and detection of biomarkers

    NASH, liver cancer, mechanism, biomarker  Individual

    2017.04 - Now 

  • Study on mechanisms of carcinogenesis: Biochemical and molecular-biological approach

    Chemical carcinogenesis, Molecular pathology, Biochemistry  Individual

    2003.04 - Now 

  • Translational research in investigation of cancer mechanisms and novel biomarkers

    Liver cancer, pancreas cancer, lung cancer, biomarker, molecular targets, translational research  Individual

    2003.04 - Now 

  • Cancer chemoprevention

    Cancer prevention, Chemoprevention  Individual

    2003.04 - Now 

  • Oxidative stress DNA damage and repair in carcinogenesis

    Individual

    2000.04 - Now 

  • Cancer risk assessment for genotoxic and non-genotoxic carcinogens

    Cancer risk assessment, Toxicologic pathology, Molecular pathology  Individual

    1999.04 - Now 

  • Study on molecular mechanisms of arsenic carcinogenicity

    arsenic, carcinogenesis, mechanism  International Joint Research

    1999.04 - Now 

Professional Memberships

  • Japanese Association for Cancer Research

      Domestic

  • Japanese Society for Carcinogenic Pathology

      Domestic

  • Society of Toxicology (USA)

      Overseas

  • Japanese Food and Chemical Association

      Domestic

  • Japanese Toxicology Association

      Domestic

  • Japanese Association for Cancer Prevention

      Domestic

  • Japanese Toxicologic Pathology Association

      Domestic

  • Japanese Pathology Association

      Domestic

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Awards

  • 高松宮妃癌研究基金学術省

    梯アンナ

    2022.04   公益財団法人   浸潤性膵管癌の早期発見や治療のための新規バイオーマーカーおよび分子ターゲットの解明

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    Country:Japan

  • 弟8回大阪市立大学女性研究者特別賞[岡村賞]

    梯アンナ

    2021.12   大阪市立大学  

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    Country:Japan

  • Osaka City Medical Association President Award 2017

    Anna Kakehashi, Naomi Ishii, Takahiro Okuno, Masaki Fujioka, Min Wei, Shoji Fukushima, Hideki Wanibuchi

    2018.03   Osaka City Medical Association   Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital

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    Country:Japan

  • Dean Award of Excellence 2017

    2018.03   Osaka City University Graduate School of Medicine   Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital Journal: Oxidative Medicine and Cellular Longevity

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    Country:Japan

  • Award for young scientists from Society of Toxicology of Japan

    Anna Kakehashi

    2003.07   JTA   Carcinogenicity of low doses of phenobarbital in the rat liver: Evidence for hormesis

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    Country:Japan

  • Award from the Chairman of Society of Toxicologic Pathology of Japan

    Phenobarbital at low dose suppresses rat hepatocarcinogenesis by altering cellproliferation, apoptosis and inhibiting oxidative DNA damage

    2002.01   JSTP  

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    Country:Japan

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Education

  • Osaka City University   Chemical carcinogenesis Cancer risk assessment Mol.pathology   Doctor's Course   Graduated/Completed

    1999 - 2003

Papers

  • Stromal area differences with epithelial-mesenchymal transition gene changes in conjunctival and orbital mucosa-associated lymphoid tissue lymphoma Reviewed

    Tagami M, Kasashima H, Kakehashi A, Yoshikawa A, Nishio M, Misawa N, Sakai A, Wanibuchi H, Yashiro M, Azumi A, Honda S

    14   1277749   2024.01( ISSN:2234-943X

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    DOI: 10.3389/fonc.2024.1277749

    PubMed

  • Evaluation of the Mechanisms Involved in the Development of Bladder Toxicity following Exposure to Occupational Bladder Cancer Causative Chemicals Using DNA Adductome Analysis Reviewed International coauthorship

    Suzuki S, Gi M, Komiya M, Obikane A, Vachiraarunwong A, Fujioka M, Kakehashi A, Totsuka Y, Wanibuchi H

    14 ( 1 )   2023.12

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    DOI: 10.3390/biom14010036

    PubMed

  • DNA Methylation Aberrations in Dimethylarsinic Acid-Induced Bladder Carcinogenesis. Reviewed

    Yamamoto T, Gi M, Yamashita S, Suzuki S, Fujioka M, Vachiraarunwong A, Guo R, Qiu G, Kakehashi A, Kato M, Uchida J, Wanibuchi H

    Cancers   15 ( 21 )   2023.11( ISSN:2072-6694

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3390/cancers15215274

    PubMed

  • Recent Insights into the Biomarkers, Molecular Targets and Mechanisms of Non-Alcoholic Steatohepatitis-Driven Hepatocarcinogenesis. Reviewed

    Kakehashi A, Suzuki S, Wanibuchi H

    Cancers   15 ( 18 )   2023.09( ISSN:2072-6694

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3390/cancers15184566

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  • Dimethylarsinic acid induces bladder carcinogenesis via the amphiregulin pathway. Reviewed

    Shugo Suzuki, Min Gi, Masaki Fujioka, Anna Kakehashi, Hideki Wanibuchi

    Toxicology Letters   384   128 - 135   2023.08( ISSN:0378-4274

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Dimethylarsinic acid (DMA) is a major metabolite in the urine of humans and rats exposed to inorganic arsenicals, and is reported to induce rat bladder carcinogenesis. In the present study, we focused on early pathways of carcinogenesis triggered by DMA that were also active in tumors. RNA expression in the bladder urothelium of rats treated with 0 and 200 ppm DMA in the drinking water for 4 weeks and in bladder tumors of rats treated with 200 ppm DMA for 2 years was initially examined using microarray analysis and Ingenuity Pathway Analysis (IPA). Expression of 160 genes was altered in both the urothelium of rats treated for 4 weeks with DMA and in DMA-induced tumors. IPA associated 36 of these genes with liver tumor diseases. IPA identified the amphiregulin (Areg)-regulated pathway as a Top Regulator Effects Network. Therefore, we focused on Areg and 6 of its target genes: cyclin A2, centromere protein F, marker of proliferation Ki-67, protein regulator of cytokinesis 1, ribonucleotide reductase M2, and topoisomerase II alpha. We confirmed high mRNA expression of Areg and its 6 target genes in both the urothelium of rats treated for 4 weeks with DMA and in DMA-induced tumors. RNA interference of human amphiregulin (AREG) expression in human urinary bladder cell lines T24 and UMUC3 decreased expression of AREG and its 6 target genes and decreased cell proliferation. These data suggest that Areg has an important role in DMA-induced rat bladder carcinogenesis.

    DOI: 10.1016/j.toxlet.2023.08.004

    PubMed

  • o-Toluidine metabolism and effects in the urinary bladder of humanized-liver mice. Reviewed

    Yuka Yokota, Shugo Suzuki, Min Gi, Yukie Yanagiba, Nao Yoneda, Masaki Fujioka, Anna Kakehashi, Shigeki Koda, Hiroshi Suemizu, Hideki Wanibuchi

    Toxicology   488   153483 - 153483   2023.04( ISSN:0300-483X

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Occupational exposure to aromatic amines is one of the most important risk factors for urinary bladder cancer. When considering the carcinogenesis of aromatic amines, metabolism of aromatic amines in the liver is an important factor. In the present study, we administered ortho-toluidine (OTD) in the diet to mice for 4 weeks. We used NOG-TKm30 mice (control) and humanized-liver mice, established via human hepatocyte transplantation, to compare differences in OTD-induced expression of metabolic enzymes in human and mouse liver cells. We also investigated OTD-urinary metabolites and proliferative effects on the urinary bladder epithelium. RNA and immunohistochemical analyses revealed that expression of N-acetyltransferases mRNA in the liver tended to be lower than that of the P450 enzymes, and that OTD administration had little effect on N-acetyltransferase mRNA expression levels. However, expression of CYP3A4 was increased in the livers of humanized-liver mice, and expression of Cyp2c29 (human CYP2C9/19) was increased in the livers of NOG-TKm30 mice. OTD metabolites in the urine and cell proliferation activities in the bladder urothelium of NOG-TKm30 and humanized-liver mice were similar. However, the concentration of OTD in the urine of NOG-TKm30 mice was markedly higher than in the urine of humanized-liver mice. These data demonstrate differences in hepatic metabolic enzyme expression induced by OTD in human and mouse liver cells, and consequent differences in the metabolism of OTD by human and mouse liver cells. This type of difference could have a profound impact on the carcinogenicity of compounds that are metabolized by the liver, and consequently, would be important in the extrapolation of data from animals to humans.

    DOI: 10.1016/j.tox.2023.153483

    PubMed

  • Safety and Feasibility of Contrast-Enhanced Computed Tomography with a Nanoparticle Contrast Agent for Evaluation of Diethylnitrosamine-Induced Liver Tumors in a Rat Model. Reviewed

    Nota T, Kageyama K, Yamamoto A, Kakehashi A, Yonezawa H, Jogo A, Sohgawa E, Murai K, Ogawa S, Miki Y

    Academic Radiology   30 ( 1 )   30 - 39   2023.01( ISSN:1076-6332

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    DOI: 10.1016/j.acra.2022.03.027

    PubMed

  • The carbonic anhydrase inhibitor acetazolamide inhibits urinary bladder cancers via suppression of β-catenin signaling. Reviewed

    Taisuke Matsue, Min Gi, Masayuki Shiota, Hirokazu Tachibana, Shugo Suzuki, Masaki Fujioka, Anna Kakehashi, Tomoki Yamamoto, Minoru Kato, Junji Uchida, Hideki Wanibuchi

    Cancer science   113 ( 8 )   2642 - 2653   2022.08( ISSN:1347-9032

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Carbonic anhydrases (CAs) play an important role in maintaining pH homeostasis. We previously demonstrated that overexpression of CA2 was associated with invasion and progression of urothelial carcinoma (UC) in humans. The purpose of the present study was to evaluate the effects of the CA inhibitor acetazolamide (Ace) on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder carcinogenesis in mice and explore the function of CA2 in muscle invasion by UC. Male mice were treated with 0.025% (experiment 1) or 0.05% BBN (experiment 2) in their drinking water for 10 weeks, then treated with cisplatin (Cis), Ace, or Cis plus Ace for 12 weeks. In experiment 1, the overall incidence of BBN-induced UCs was significantly decreased in the BBN→Ace and BBN→Cis+Ace groups. In experiment 2, the overall incidence of BBN-induced UCs was significantly decreased in the BBN→Cis+Ace group, and the incidence of muscle invasive UC was significantly decreased in both the BBN→Ace and the BBN→Cis+Ace groups. We also show that overexpression of CA2 by human UC cells T24 and UMUC3 significantly increased their migration and invasion capabilities, and that Ace significantly inhibited migration and invasion by CA2-overexpressing T24 and UMUC3 cells. These data demonstrate a functional association of CA2 with UC development and progression, confirming the association of CA2 with UC that we had shown previously by immunohistochemical analysis of human UC specimens and proteome analysis of BBN-induced UC in rats. Our finding that inhibition of CA2 inhibits UC development and muscle invasion also directly confirms that CA2 is a potential therapeutic target for bladder cancers.

    DOI: 10.1111/cas.15467

    PubMed

  • Response biomarkers of inhalation exposure to cigarette smoke in the mouse lung Reviewed

    Suzuki Shugo, Asai Kazuhisa, Gi Min, Kojima Kazuya, Kakehashi Anna, Oishi Yuji, Matsue Taisuke, Yukimatsu Nao, Hirata Kazuto, Kawaguchi Tomoya, Wanibuchi Hideki

    Journal of Toxicologic Pathology   35 ( 3 )   247 - 254   2022.07( ISSN:0914-9198 ( eISSN:1881915X

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    <p> Cigarette smoking is known to increase the risk of cancer and chronic obstructive pulmonary disease (COPD). In this study, we evaluated the effects of short-term nose-only inhalation exposure to cigarette smoke in mice. Male 10-week-old C57BL mice were exposed to clean air (control) or mainstream cigarette smoke for 1 h/day, 5 days/week, for 2 or 4 weeks. Exposure to cigarette smoke increased the number of inflammatory cells, especially neutrophils, in the bronchoalveolar lavage fluid, increased inflammatory cell infiltration foci, and caused an increase in the thickness of the peripheral bronchial epithelium. Microarray gene expression analysis indicated that smoke exposure induced inflammatory responses, including leukocyte migration and activation of phagocytes and myeloid cells, as early as two weeks after the initiation of exposure. Importantly, chemokine (C-C motif) ligand 17, resistin-like alpha, and lipocalin 2 were upregulated and may serve as useful markers of the toxic effects of exposure to cigarette smoke before pulmonary histological changes become evident.</p>

    DOI: 10.1293/tox.2021-0077

    PubMed

  • FOXP3 and CXCR4-positive regulatory T cells in the tumor stroma as indicators of tumor immunity in the conjunctival squamous cell carcinoma microenvironment. Reviewed

    Tagami M, Kakehashi A, Katsuyama-Yoshikawa A, Misawa N, Sakai A, Wanibuchi H, Azumi A, Honda S

    PloS one   17 ( 3 )   e0263895   2022

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1371/journal.pone.0263895

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  • Expression of thrombospondin-1 in conjunctival squamous cell carcinoma is correlated to the Ki67 index and associated with progression-free survival. Reviewed

    Tagami M, Kakehashi A, Sakai A, Misawa N, Katsuyama-Yoshikawa A, Wanibuchi H, Azumi A, Honda S

    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie   259 ( 10 )   3127 - 3136   2021.10( ISSN:0721-832X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00417-021-05236-7

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  • Canopy Homolog 2 as a Novel Molecular Target in Hepatocarcinogenesis. Reviewed

    Anna Kakehashi, Shugo Suzuki, Masayuki Shiota, Nina Raymo, Min Gi, Taro Tachibana, Vasily Stefanov, Hideki Wanibuchi

    Cancers   13 ( 14 )   2021.07( ISSN:2072-6694

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    In the present study, the role of a novel protein involved in neurite development and endoplasmic reticulum (ER) stress, canopy homolog 2 (CNPY2), was investigated in mouse and human hepatocarcinogenesis. Firstly, a sensitive quantitative and qualitative detection of protein expression using QSTAR Elite LC-Ms/Ms was performed for the analysis of lysates of microdissected hepatocellular altered foci (AF), adenomas (HCAs), carcinomas (HCCs) and peri-tumoral livers from C57Bl/6J mice treated with diethylnitrosamine (DEN) and then maintained for 27 or 38 weeks on basal diet. Significant overexpression of 18.5 kDa CNPY2 processed form was demonstrated in AF, HCAs and HCCs, while low expression was observed in the livers of DEN-treated and control mice. Furthermore, CNPY2 elevation in AF and tumors was coordinated with accumulation of numerous cytoskeletal proteins, including cytokeratins 8 and 18, actin, non-muscle myosin and septin 9 and those involved in ER and mitochondrial stresses such as calreticulin, prohibitins 1 and 2 and YME1-like-1. Knockdown of CNPY2 in Huh7 and HepG2 human liver cancer cells resulted in significant suppression of cell survival and invasive potential, inhibition of cyclin D1, induction of p21Waf1/Cip1 and suppression of the apoptosis inhibitor Bcl2. In contrast, transfection of a mouse CNPY2 (mCNPY2-Ds-Red) vector plasmid in Huh7 and HepG2 cancer cells, with subsequent accumulation of CNPY2 in the ER, resulted in significant increase in cancer cells survival. Clinicopathological analysis in 90 HCV-positive HCC patients, revealed significant association of CNPY2 overexpression with poor overall (p = 0.041) survival. Furthermore, CNPY2 increase was associated with vessel invasion (p = 0.038), poor histological differentiation (p = 0.035) and advanced clinical stage (p = 0.016). In conclusion, CNPY2 is a promising molecular target elevated early in hepatocarcinogenesis and prognostic marker for human HCV-associated HCC. CNPY2 is involved in the processes of ER stress, cell cycle progression, proliferation, survival and invasion of liver tumor cells.

    DOI: 10.3390/cancers13143613

    PubMed

  • Cache Domain Containing 1 Is a Novel Marker of Non-Alcoholic Steatohepatitis-Associated Hepatocarcinogenesis Reviewed International coauthorship

    13 ( 6 )   1216   2021.03

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work  

  • Accumulation of 8-hydroxydeoxyguanosine, L-arginine and glucose metabolites by liver tumor cells are the important characteristic features of metabolic syndrome and non-alcoholic steatohepatitis-associated hepatocarcinogenesis Reviewed International coauthorship

    Anna Kakehashi, Shugo Suzuki, Naomi Ishii, Takahiro Okuno, Yuko Kuwae, Masaki Fujioka, Min Gi, Vasily Stefanov, Hideki Wanibuchi

    International Journal of Molecular Sciences   21 ( 20 )   7746   2020.10

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work  

    To uncover mechanisms and explore novel biomarkers of obesity, type 2 diabetes (T2DM) and nonalcoholic steatohepatitis (NASH)-associated hepatocarcinogenesis, cellular and molecular alterations in the liver, and hepatocellular carcinomas (HCCs) were investigated in NASH model 60-week-old Tsumura, Suzuki, Obese Diabetic (TSOD) mice and NASH HCC patients. Markedly elevated lipid deposition, inflammation, fibrosis, and peroxisome proliferation in the liver, preneoplastic lesions, and HCCs of TSOD mice were accompanied by accumulation of polysaccharides in the cellular cytoplasm and nuclei and increase of oxidative DNA damage marker, 8-hydroxydeoxyguanosine (8-OHdG) formation in the liver and altered foci. Metabolomics of TSOD mice HCCs demonstrated significant elevation of the concentration of amino acid L-arginine, phosphocreatine, S-adenosylmethionine/S-adenosylhomocysteine ratio, adenylate, and guanylate energy charges in coordination with tremendous rise of glucose metabolites, mostly fructose 1,6-diphosphate. L-arginine accumulation in HCCs was associated with significant under-expression of arginase 1 (ARG1), suppression of the urea cycle, methionine and putrescine degradation pathways, activation of Ser and Thr kinase Akt AKT, phosphoinositide 3-kinase (PI3K), extracellular signal-regulated kinase 1/2 (ERK1/2) kinases, β-catenin, mammalian target of rapamycin (mTOR), and cell proliferation. Furthermore, clinicopathological analysis in 20 metabolic syndrome/NASH and 80 HCV-positive HCC patients demonstrated significant correlation of negative ARG1 expression with poor tumor differentiation, higher pathological stage, and significant decrease of survival in metabolic syndrome/NASH-associated HCC patients, thus indicating that ARG1 could become a potential marker for NASH HCC. From these results, formation of oxidative stress and 8-OHdG in the DNA and elevation of glucose metabolites and L-arginine due to ARG1 suppression in mice liver cells are the important characteristics of T2DM/NASH-associated hepatocarcinogenesis, which may take part in activating oxidative stress resistance, synthesis of phosphocreatine, cell signaling, methylation, and proliferation.

  • Expression, intracellular localization, and mutation of EGFR in conjunctival squamous cell carcinoma and the association with prognosis and treatment Reviewed

    Atsushi Sakai, Mizuki Tagami, Anna Kakehashi, Atsuko Katsuyama-Yoshikawa, Norihiko Misawa, Hideki Wanibuchi, Atsushi Azumi, Shigeru Honda

    PLoS One   15 ( 8 )   e0238120   2020.08

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work  

  • Role of γ-H2AX as a biomarker for detection of bladder carcinogens in F344 rats. Reviewed

    Shugo Suzuki, Min Gi, Takeshi Toyoda, Hiroyuki Kato, Aya Naiki-Ito, Anna Kakehashi, Kumiko Ogawa, Satoru Takahashi, Hideki Wanibuchi

    Journal of Toxicologic Pathology   33 ( 4 )   279 - 285   2020.08

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work   International / domestic magazine:International journal  

  • Dimethylarsinic acid (DMA) enhanced lung carcinogenesis via histone H3K9 modification in a transplacental mouse model Reviewed

    Fujioka Masaki, Suzuki Shugo, Gi Min, Kakehashi Anna, Oishi Yuji, Okuno Takahiro, Yukimatsu Nao, Wanibuchi Hideki

    ARCHIVES OF TOXICOLOGY   2020.02( ISSN:0340-5761

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work  

    以前の研究では妊娠中のCD-1マウスは、妊娠8〜18日目から飲料水に200ppmのジメチルアルシン酸(DMA)を投与され、84週齢の子孫で腫瘍形成が評価された。 DMAは、雄のコントロールの子孫と比較して、肺腺癌(10.0%)および総腫瘍(33.3%)の発生率を上昇させた。 また、雄の子孫における肝細胞癌の発生率(10.0%)も上昇した。 DMAとその代謝物は、DMA処理新生児マウスの肺で検出された。マイクロアレイおよびリアルタイムPCR分析により、新生児および6週齢のDMA処理マウスの肺でkeratin 8(Krt8)の高発現が検出された。また、ウエスタンブロット分析は、DMAが雄マウスの肺ではヒストンH3K9のメチル化を上昇した。H3K9me3抗体を使用したクロマチン免疫沈降シーケンス(ChIP-seq)分析により、DMAとコントロール群マウスの間ではヘテロクロマチン形成に違いが見られた。Krt8の高発現は、雄の子孫の肺の腺腫および腺癌でも検出された。これらのデータは、経胎盤DMA治療が雄マウスの肺および肝臓の発癌を促進した。肺では、DMAはヒストンH3K9の異常なメチル化を引き起こし、Krt8発現を増加させ、細胞増殖を促進した。

    DOI: 10.1007/s00204-020-02665-x

    PubMed

  • Promotion effects of acetoaceto-o-toluidide on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder carcinogenesis in rats Reviewed

    Yukimatsu Nao, Gi Min, Okuno Takahiro, Fujioka Masaki, Suzuki Shugo, Kakehashi Anna, Yanagiba Yukie, Suda Megumi, Koda Shigeki, Nakatani Tatsuya, Wanibuchi Hideki

    ARCHIVES OF TOXICOLOGY   93 ( 12 )   3617 - 3631   2019.12( ISSN:0340-5761

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    最近の疫学研究は、アミンアセトアセト-o-トルイジド(AAOT)の職業的曝露により日本では膀胱癌の著しい増加が見られた。しかし、AAOTの発がん性についてはほとんど知られていない。 AAOTの膀胱発がん性を評価するために、雄と雌のF344ラットをN-ブチル-N-(4-ヒドロキシブチル)ニトロソアミン(BBN)で4週間処理した後、31週間を0、0.167、0.5、または1.5%AAOTの混じ投与を行った。その結果、雄と雌ラットの0.5および1.5%AAOT群では膀胱腫瘍の発生率と個数は、有意に増加した。 尿中にAAOTの最も多い代謝産物(ヒト膀胱発がん物質)o-トルイジン(OTD)のレベルが上昇していた。遺伝子発現解析により、JUNとその下流の標的遺伝子の発現は、1.5%AAOTを投与した雄ラットの尿路上皮で増加したことが明らかになった。これらの結果は、AAOTがラットのBBN誘発膀胱発がんを促進し、JUNとその下流の標的遺伝子の過剰発現がAAOTの膀胱発がん性に関与している可能性を示唆された。

    DOI: 10.1007/s00204-019-02605-4

    PubMed

  • Quantitative analysis of mutagenicity and carcinogenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in F344 gpt delta transgenic rats Reviewed

    Gi Min, Fujioka Masaki, Totsuka Yukari, Matsumoto Michiharu, Masumura Kenichi, Kakehashi Anna, Yamaguchi Takashi, Fukushima Shoji, Wanibuchi Hideki

    MUTAGENESIS   34 ( 3 )   279 - 287   2019.05( ISSN:0267-8357

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    本研究では、低用量の食餌性遺伝毒性発がん物質2-アミノ-3-メチルイミダゾ[4,5-f]キノリン(IQ)の変異原性と発がん性を検討した。雄のF344 gpt deltaトランスジェニックラットに、0、0.1、1、10、または100 ppmの4週間をIQを混じ投与した。10および100 ppm群では肝臓のgpt導入遺伝子変異の頻度は、有意に増加した。さらに、1、10、100 ppm群で変異スペクトルが変更した。1、10、100 ppmのIQを用量した肝臓では依存的に、G:CからT:Aの変異が増加した。また、 100 ppm G:CからA:T、A:TからT:AおよびA:TからC:Gへの移行の頻度は上昇した。100 ppm群ではラットの肝臓の前がん病変であるGST-P陽性病巣の増加も観察された。

    DOI: 10.1093/mutage/gez015

    PubMed

  • Acetoaceto-o-toluidide enhances cellular proliferative activity in the urinary bladder of rats. Reviewed

    Takahiro Okuno, Min Gi, Masaki Fujioka, Nao Yukimatu, Anna Kakehashi, Akito Takeuchi , Gingi Endo , Yoko Endo, Hideki Wanibuchi

    TOXICOLOGICAL SCIENCES   169 ( 2 )   456 - 464   2019.02( ISSN:1096-6080

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    Acetoaceto-o-toluidide (AAOT) is made from ortho-toluidine (OTD) and is used for the synthesis of pigments. A report of occupational urinary bladder carcinomas in Japanese workers chronically exposed to OTD and AAOT has recently been published. OTD is a well-known human urinary bladder carcinogen; however, little is known about the toxicity and the carcinogenicity of AAOT. The aim of the present study is to evaluate the toxic effects of AAOT on urinary bladder epithelium. In vitro, the cytotoxicities of AAOT and OTD were evaluated in rat (MYP3) and human (1T1) urothelial cells. The LC50 of AAOT was higher than that of OTD in both MYP cells and 1T1 cells. In vivo, 6-week-old male and female F344 rats were fed diets supplemented with 0%, 1.5%, or 3% AAOT for 4 weeks. Incidences of simple hyperplasia, cell proliferative activity, and γ-H2AX expression, which is a novel marker for the prediction of carcinogenicity, were significantly increased in a dose-dependent manner in the bladder urothelium of male and female rats administered AAOT. Furthermore, in male and female rats administered AAOT, the major urine metabolite of AAOT was OTD. These results demonstrate that AAOT has proliferation-enhancing activity and suggest that OTD metabolized from AAOT may play a pivotal role in the deleterious effects of AAOT in rats. The results of the present study also indicate that AAOT, like other carcinogenic aromatic amines, is likely to be a human bladder carcinogen.

    DOI: 10.1093/toxsci/kfz051

    PubMed

  • A chronic toxicity study of diphenylarsinic acid in the drinking water of C57BL/6J mice for 52 weeks. Reviewed

    Takashi Yamaguchi, Min Gi, Masaki Fujioka, Yoshiyuki Tago, Anna Kakehashi, Hideki Wanibuchi

    JOURNAL OF TOXICOLOGIC PATHOLOGY   32 ( 3 )   127 - 134   2019( ISSN:0914-9198

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    Diphenylarsinic acid (DPAA), a neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping. The purpose of the present study was to evaluate the potential toxicity of DPAA when administered to mice in their drinking water for 52 weeks. DPAA was administered to mice at concentrations of 0, 6.25, 12.5, and 25 ppm in their drinking water for 52 weeks. There were no significant differences in final body weights between the control groups and the DPAA treatment groups in male or female mice. Relative liver weights were significantly increased in males treated with 25 ppm DPAA, and absolute liver weights were significantly decreased in female mice treated with 25 ppm DPAA. In female mice, cholangitis and simple bile duct hyperplasia were observed in the 12.5 and 25 ppm DPAA groups, and focal necrosis of hepatocytes was observed in the 25 ppm DPAA group. Proteomic analysis and Ingenuity Pathway Analysis identified 18 proteins related to hepatotoxicity that were overexpressed in the female 25 ppm group. The phase I metabolic enzyme CYP2E1 was one of these overexpressed proteins. Immunostaining confirmed high expression of CYP2E1 in the livers of females in the 25 ppm group. These results suggest that DPAA is toxic to the intrahepatic bile duct epithelium and hepatocytes in female mice and that CYP2E1 might be involved in DPAA-associated toxicity. The no-observed-adverse-effect levels of DPAA were 12.5 ppm for males and 6.25 ppm for females under the conditions of this study.

    DOI: 10.1293/tox.2018-0067

    CiNii Article

  • Chronic dietary toxicity and carcinogenicity studies of dammar resin in F344 rats. Reviewed

    Min Gi, Masaki Fujioka, Shotaro Yamano, Anna Kakehashi, Yuji Oishi, Takahiro Okuno, Nao Yukimatsu, Takashi Yamaguchi, Yoshiyuki Tago, Mitsuaki Kitano, Shim-mo, Hideki Wanibuchi

    ARCHIVES OF TOXICOLOGY   92 ( 12 )   3565 - 3583   2018.12( ISSN:0340-5761

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    DOI: 10.1007/s00204-018-2316-7

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  • Steroid sulfatase promotes invasion through epithelial-mesenchymal transition and predicts the progression of bladder cancer. Reviewed

    Yasuomi Shimizu, Satoshi Tamada, Minoru Kato, Yuji Takeyama, Masaki Fujioka, Anna Kakehashi, Tatsuya Nakatani, Hideki Wanibuchi, Min Gi

    EXPERIMENTAL AND THERAPEUTIC MEDICINE   16 ( 6 )   4463 - 4470   2018.12( ISSN:1792-0981

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    DOI: 10.3892/etm.2018.6787

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  • mTOR activation in liver tumors is associated with metabolic syndrome and non-alcoholic steatohepatitis in both mouse models and humans. Reviewed

    Takahiro Okuno, Anna Kakehashi, Naomi Ishii, Masaki Fujioka, Min Gi, Hideki Wanibuchi

    CANCERS   10 ( 12 )   2018.12( ISSN:2072-6694

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    DOI: 10.3390/cancers10120465

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  • Quantitative Approaches to Assess Key Carcinogenic Events of Genotoxic Carcinogens. Reviewed

    Shoji Fukushima, Min Gi, Masaki Fujioka, Anna Kakehashi, Hideki Wanibuchi, Michiharu Matsumoto

    TOXICOLOGICAL RESEARCH   34 ( 4 )   291 - 296   2018.10( ISSN:1976-8257

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    DOI: 10.5487/TR.2018.34.4.291

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  • In vivo positive mutagenicity of 1,4-dioxane and quantitative analysis of its mutagenicity and carcinogenicity in rats. Reviewed

    Min Gi, Masaki Fujioka, Anna Kakehashi, Takahiro Okuno, Kenichi Masumura, Takehiko Nohmi, Michiharu Matsumoto, Masako Omori, Hideki Wanibuchi, Shoji Fukushima

    ARCHIVES OF TOXICOLOGY   92 ( 10 )   3207 - 3221   2018.10( ISSN:0340-5761

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    DOI: 10.1007/s00204-018-2282-0

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  • Carcinogenicity induced by prenatal exposure to dimethylarsinic acid in CD1 mice Reviewed

    Masaki Fujioka, Min Gi, Kenji Kumada, Takahiro Okuno, Anna Kakehashi, Hideki Wanibuchi

    CANCER SCIENCE   109   584 - 584   2018.01( ISSN:1349-7006

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  • Roles of Ink4a/Arf in BBN-induced mouse bladder carcinogenesis Reviewed

    Kohyama Yuki, Gi Min, Fujioka Masaki, Kumada Kenji, Okuno Takahiro, Kakehashi Anna, Wanibuchi Hideki

    CANCER SCIENCE   109   167 - 167   2018.01( ISSN:1349-7006

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  • Proteome characteristics of non-alcoholic steatohepatitis liver tissue and associated hepatocellular carcinomas. Reviewed

    109   584 - 584   2018.01( ISSN:1349-7006

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  • Inhibitory effects of acetazolamide on the BBN-induced mouse bladder carcinogenesis Reviewed

    Min Gi , Masaki Fujioka, Anna Kakehashi, Takahiro Okuno, Yuki Kouyama, Kenji Kumada, Hideki Wanibuchi

    CANCER SCIENCE   109   305 - 305   2018.01( ISSN:1349-7006

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  • Enhanced Susceptibility of Ogg1 Mutant Mice to Multiorgan Carcinogenesis Reviewed

    Kakehashi Anna, Ishii Naomi, Okuno Takahiro, Fujioka Masaki, Gi Min, Wanibuchi Hideki

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   18 ( 8 )   2017.08( ISSN:1422-0067

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    DOI: 10.3390/ijms18081801

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  • F344ラットへのジフェニルアルシン酸含有飲料水104週間投与の発癌性に関する検討(A carcinogenicity study of diphenylarsinic acid in F344 rats in drinking water for 104 weeks) Reviewed

    Yamaguchi Takashi, Gi Min, Fujioka Masaki, Doi Kenichiro, Okuno Takahiro, Kakehashi Anna, Wanibuchi Hideki

    (一社)日本毒性学会 The Journal of Toxicological Sciences   42 ( 4 )   475 - 483   2017.08( ISSN:0388-1350

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    ジフェニルアルシン酸(DPAA)含有飲料水を雌雄F344ラットに104週間摂取させ、過去に52週間DPAAを投与した際に認められた肝内胆管肥厚が腫瘍に進展するか否かを含め、DPAAによる発癌性を検討した。雌雄ラットを4群に分け、飲料水中のDPAA濃度を0、5、10、20ppmの4段階に設定し、雌雄の群間で発癌性を比較した。その結果、雌性20ppm群では有意な生存率の低下を認め、雄性20ppm群と雌性10、20ppm群では有意な体重の減少を認めた。全組織における腫瘍の包括的組織病理学的検査では、雌雄ラットの全群で、どの器官にも腫瘍発生率の有意な上昇を認めなかった。以上より、DPAAは雌雄F344ラットの発癌物質ではないと考えられた。

  • Carbonic anhydrase 2 is a novel invasion-associated factor in urinary bladder cancers Reviewed

    Tachibana Hirokazu, Gi Min, Kato Minoru, Yamano Shotaro, Fujioka Masaki, Kakehashi Anna, Hirayama Yukiyoshi, Koyama Yuki, Tamada Satoshi, Nakatani Tatsuya, Wanibuchi Hideki

    CANCER SCIENCE   108 ( 3 )   331 - 337   2017.03( ISSN:1349-7006

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    DOI: 10.1111/cas.13143

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  • Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas Reviewed

    Kakehashi Anna, Stefanov Vasily E., Ishii Naomi, Okuno Takahiro, Fujii Hideki, Kawai Kazuaki, Kawada Norifumi, Wanibuchi Hideki

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   18 ( 2 )   2017.02( ISSN:1422-0067

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    DOI: 10.3390/ijms18020434

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  • A chronic toxicity study of diphenylarsinic acid in F344 rats in drinking water for 52 weeks Reviewed

    Yamaguchi Takashi, Gi Min, Yamano Shotarou, Fujioka Masaki, Tatsumi Kumiko, Kawachi Satoko, Ishii Naomi, Doi Kenichiro, Kakehashi Anna, Wanibuchi Hideki

    EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY   69 ( 1 )   1 - 7   2017.01( ISSN:0940-2993

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    DOI: 10.1016/jetp.2016.10.002

  • A carcinogenicity study of diphenylarsinic acid in F344 rats in drinking water for 104 weeks. Reviewed

    Yamaguchi T, Gi M, Fujioka M, Doi K, Okuno T, Kakehashi A, Wanibuchi H

    一般社団法人 日本毒性学会 The Journal of toxicological sciences   42 ( 4 )   475 - 483   2017( ISSN:0388-1350

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    <p>Diphenylarsinic acid (DPAA), a neurotoxic organic arsenical used as a chemical warfare agent, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. We previously demonstrated that DPAA promotes diethylnitrosamine-induced liver carcinogenesis in a medium-term rat liver bioassay. The purpose of the present study was to evaluate the potential carcinogenicity of DPAA, including investigation of whether the bile duct hyperplasia in the liver that was observed in a previous 52 week rat chronic study develops into a tumor, when administered to rats in their drinking water for 104 weeks. DPAA was administered to groups 1-4 at concentrations of 0, 5, 10, and 20 ppm in their drinking water for 104 weeks. A significant decrease in survival rate was found for females in the 20 ppm DPAA group. Body weights of males in the 20 ppm and females in the 10 and 20 ppm DPAA groups were significantly decreased compared to the controls. Overall histopathological evaluation of neoplasms in all tissues showed no significant increase of tumor incidence in any organ or tissue of the 5, 10, or 20 ppm DPAA-treated male or female F344 rats. In conclusion, the present study demonstrated that DPAA is not a complete carcinogen in male or female F344 rats.</p>

    DOI: 10.2131/jts.42.475

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  • Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital Reviewed

    Kakehashi Anna, Ishii Naomi, Okuno Takahiro, Fujioka Masaki, Gi Min, Fukushima Shoji, Wanibuchi Hideki

    OXIDATIVE MEDICINE AND CELLULAR LONGEVITY   2017   8541064   2017( ISSN:1942-0900

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    DOI: 10.1155/2017/8541064

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  • Chemopreventive Action by Ethanol-extracted Brazilian Green Propolis on Post-initiation Phase of Inflammation-associated Rat Colon Tumorigenesis Reviewed

    Doi Kenichiro, Fujioka Masaki, Sokuza Yui, Ohnishi Mariko, Gi Min, Takeshita Masanori, Kumada Kenji, Kakehashi Anna, Wanibuchi Hideki

    IN VIVO   31 ( 2 )   187 - 197   2017( ISSN:0258-851X

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    DOI: 10.21873/invivo.11044

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  • Diphenylarsinic acid exerts promotion effects on hepatobiliary carcinogenesis in a rat medium-term multiorgan carcinogenicity bioassay Reviewed

    Ishii Naomi, Gi Min, Fujioka Masaki, Yamano Shotaro, Okumura Mai, Kakehashi Anna, Wanibuchi Hideki

    日本毒性病理学会 JOURNAL OF TOXICOLOGIC PATHOLOGY   30 ( 1 )   39 - 45   2017( ISSN:0914-9198

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    <p> We have previously demonstrated that diphenylarsinic acid (DPAA) promotes liver carcinogenesis in rats in a medium-term liver carcinogenicity bioassay. However, the effects of DPAA on other organs have not been determined. In the present study, the effects of DPAA on carcinogenesis were investigated using a rat multiorgan carcinogenicity bioassay. A total of 60 six-week-old male F344 rats were treated with the carcinogens diethylnitrosamine, N-butyl-N-(4-hydroxybutyl) nitrosamine, N-methyl-N-nitrosourea, N-bis (2-hydroxypropyl) nitrosamine, and 1,2-dimethylhydrazine dihydrochloride to initiate carcinogenesis in multiple organs. After initiation, DPAA was given at a dose of 0, 5, or 20 ppm in drinking water for 27 weeks. The incidences of moderate and severe bile duct hyperplasia were significantly increased in the 20 ppm DPAA group (29.4%, 70.6%, respectively) compared with the 0 ppm DPAA group (0%, 0%, respectively), and the incidence and multiplicity of cholangioma were significantly increased in the 20 ppm DPAA group (29.4%, 0.4 ± 0.8/rat) compared with the 0 ppm DPAA group (0%, 0/rat). The total number and average area of glutathione S-transferase placenta form-positive foci, preneoplastic lesions in rat livers, were significantly increased in the 20 ppm DPAA group (10.5 ± 2.2/cm<sup>2</sup>, 5.3 ± 1.7 mm<sup>2</sup>/cm<sup>2</sup>) compared with the 0 ppm DPAA group (6.2 ± 2.9/cm<sup>2</sup>, 2.4 ± 1.4 mm<sup>2</sup>/cm<sup>2</sup>). In conclusion, our results demonstrate that DPAA promotes hepatobiliary carcinogenesis in a rat medium-term multiorgan carcinogenicity bioassay; no promotion effects were observed in other organs.</p>

    DOI: 10.1293/tox.2016-0049

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  • Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats Reviewed

    Fujioka Masaki, Gi Min, Kawachi Satoko, Tatsumi Kumiko, Ishii Naomi, Doi Kenichiro, Kakehashi Anna, Wanibuchi Hideki

    JOURNAL OF ENVIRONMENTAL SCIENCES-CHINA   49   125 - 130   2016.11( ISSN:1001-0742

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    DOI: 10.1016/j.jes.2016.07.005

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  • Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats Reviewed

    Kakehashi Anna, Yoshida Midori, Tago Yoshiyuki, Ishii Naomi, Okuno Takahiro, Gi Min, Wanibuchi Hideki

    TOXINS   8 ( 11 )   2016.11( ISSN:2072-6651

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    DOI: 10.3390/toxins8110275

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  • Ethanol-Extracted Brazilian Propolis Exerts Protective Effects on Tumorigenesis in Wistar Hannover Rats Reviewed

    Kakehashi Anna, Ishii Naomi, Fujioka Masaki, Doi Kenichiro, Gi Min, Wanibuchi Hideki

    PLOS ONE   11 ( 7 )   e0158654   2016.07( ISSN:1932-6203

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    DOI: 10.1371/journal.pone.0158654

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  • Qualitative and Quantitative Assessments on Low-Dose Carcinogenicity of Genotoxic Hepatocarcinogens: Dose-Response for Key Events in Rat Hepatocarcinogenesis Reviewed

    Shoji Fukushima, Min Gi, Anna Kakehashi, Hideki Wanibuchi

    Thresholds of Genotoxic Carcinogens: From Mechanisms to Regulation   1 - 17   2016.05

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    This chapter provides quantitative data on key events in rat hepatocarcinogenesis of three genotoxic carcinogens: 2-amino-3,8-dimethylimidazo[4,5-. f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-. f]quinoline (IQ), and N-nitrosodiethylamine (DEN). MeIQx at very low doses increased formation of DNA-MeIQx adducts
    somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) DNA damage
    at still higher doses gene mutations occurred
    the much higher doses induced formation of glutathione S-transferase placental form (GST-P)-positive foci which are preneoplastic lesions. These data indicate that key events of MeIQx carcinogenesis showed the expected trend of doses for quantitative assessment. Similarly, only the highest dose of IQ caused an increase in the number of GST-P-positive foci in the liver, while IQ-DNA adduct formation was observed with very low doses. Moreover, treatment with DEN at low doses had no observed effect on the development of GST-P-positive foci in the liver. These data contribute to understand that genotoxic carcinogens have a threshold, at least a practical threshold for their carcinogenicity.

    DOI: 10.1016/B978-0-12-801663-3.00001-7

  • CD44 variant 9 is a potential biomarker of tumor initiating cells predicting survival outcome in hepatitis C virus-positive patients with resected hepatocellular carcinoma Reviewed

    Kakehashi Anna, Ishii Naomi, Sugihara Eiji, Gi Min, Saya Hideyuki, Wanibuchi Hideki

    CANCER SCIENCE   107 ( 5 )   609 - 618   2016.05( ISSN:1349-7006

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    DOI: 10.1111/cas.12908

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  • Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens Reviewed

    Fukushima Shoji, Gi Min, Kakehashi Anna, Wanibuchi Hideki, Matsumoto Michiharu

    MUTAGENESIS   31 ( 3 )   341 - 346   2016.05( ISSN:0267-8357

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    DOI: 10.1093/mutage/gev049

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  • Preventive Effects of Spirogyra neglecta and a Polysaccharide Extract against Dextran Sodium Sulfate Induced Colitis in Mice. Reviewed

    Taya S, Kakehashi A, Wongpoomchai R, Gi M, Ishii N, Wanibuchi H

    Asian Pacific journal of cancer prevention : APJCP   17 ( 4 )   2235 - 45   2016( ISSN:1513-7368

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  • Modifying effects of 1,2-dichloropropane on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in male Syrian hamsters Reviewed

    Gi Min, Fujioka Masaki, Yamano Shotaro, Shimomura En I., Kanki Masayuki, Kawachi Satoko, Tachibana Hirokazu, Tatsumi Kumiko, Fang He, Ishii Naomi, Kakehashi Anna, Wanibuchi Hideki

    JOURNAL OF TOXICOLOGICAL SCIENCES   40 ( 5 )   647 - 656   2015.10( ISSN:0388-1350

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  • Ethanol-extracted propolis enhances BBN-initiated urinary bladder carcinogenesis via non-mutagenic mechanisms in rats Reviewed

    Xie Xiao-Li, Gi Min, Fujioka Masaki, Doi Kenichiro, Yamano Shotaro, Tachibana Hirokazu, Fang He, Kakehashi Anna, Wanibuchi Hideki

    FOOD AND CHEMICAL TOXICOLOGY   83   193 - 200   2015.09( ISSN:0278-6915

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    DOI: 10.1016/j.fct.2015.06.007

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  • Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model Reviewed

    Fukunaga Satoki, Kakehashi Anna, Sumida Kayo, Kushida Masahiko, Asano Hiroyuki, Gi Min, Wanibuchi Hideki

    TOXICOLOGY AND APPLIED PHARMACOLOGY   286 ( 3 )   188 - 197   2015.08( ISSN:0041-008X

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    DOI: 10.1016/j.taap.2015.04.014

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  • Novel biomarkers for gastric cancer stem cells utilizing comparative proteomics analysis Reviewed

    Yashiro Masakazu, Morisaki Tamami, Hasegawa Tsuyoshi, Kakehashi Anna, Kinoshita Haruhito, Fukuoka Tatsunari, Kasashima Hiroaki, Masuda Go, Sakurai Katsunobu, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Wanibuchi Hideki, Hirakawa Kosei

    CANCER RESEARCH   75   2015.08( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2015-1405

  • Determination of Hepatotoxicity and Its Underlying Metabolic Basis of 1,2-Dichloropropane in Male Syrian Hamsters and B6C3F1 Mice Reviewed

    Gi Min, Fujioka Masaki, Yamano Shotaro, Shimomura Eri, Ishii Naomi, Kakehashi Anna, Takeshita Masanori, Wanibuchi Hideki

    TOXICOLOGICAL SCIENCES   145 ( 1 )   196 - 208   2015.05( ISSN:1096-6080

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    DOI: 10.1093/toxsci/kfv045

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  • Paraneoplastic Ma Antigen-Like 1 as a Potential Prognostic Biomarker in Human Pancreatic Ductal Adenocarcinoma Reviewed

    Kuwae Yuko, Kakehashi Anna, Wakasa Kenichi, Wei Min, Yamano Shotaro, Ishii Naomi, Ohsawa Masahiko, Wanibuchi Hideki

    PANCREAS   44 ( 1 )   106 - 115   2015.01( ISSN:0885-3177

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    DOI: 10.1097/MPA.0000000000000220

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  • エチル-ターシャリー-ブチルエーテルを短期投与したラット肝臓における細胞増殖の誘導(Induction of cell proliferation in the rat liver by the short-term administration of ethyl tertiary-butyl ether) Reviewed

    Kakehashi Anna, Hagiwara Akihiro, Imai Norio, Wei Min, Fukushima Shoji, Wanibuchi Hideki

    日本毒性病理学会 Journal of Toxicologic Pathology   28 ( 1 )   27 - 32   2015.01( ISSN:0914-9198

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    F344ラットへの短期間での高用量エチル-tertiary-ブチルエーテル(ETBE)投与が肝細胞増殖に与える影響について検討した。F344ラットに1000mg/kg(発癌促進効果を示す量の2倍量)のETBEを1日2回、3、10、17および28日間投与した。ETBE投与群では対照群に比べ、肝重量と腎重量が有意に増加した。顕微鏡的変化は肝臓でのみ認められ、ETBE投与群では全ての時点で肝肥大が見られた(day3で33%、day10で60%、day17およびday28で100%)。ETBE投与期間が3日から28日に増えるに従い、肝肥大の程度も亢進した。ETBE投与群ではday17においてアポトーシス細胞数が増加し、またday3およびday28におけるETBE投与群の肝細胞の有糸分裂は対照群に比べ増大していた。ETBEの短期投与は細胞増殖活性を増大させ、再生的細胞増殖を誘導することにより、以上、肝癌発癌作用に寄与すると考えられた。

  • Induction of cell proliferation in the rat liver by the short-term administration of ethyl tertiary-butyl ether. Reviewed

    Kakehashi A, Hagiwara A, Imai N, Wei M, Fukushima S, Wanibuchi H

    日本毒性病理学会 Journal of toxicologic pathology   28 ( 1 )   27 - 32   2015.01( ISSN:0914-9198

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    In the present study, in continuation of our previous experiment in order to investigate the mode of action (MOA) of ethyl <i>tertiary</i>-butyl ether (ETBE) hepatotumorigenicity in rats, we aimed to examine alterations in cell proliferation, that are induced by short-term administration of ETBE. F344 rats were administered ETBE at doses of 0, and 1,000 mg/kg body weight twice a day by gavage for 3, 10, 17 and 28 days. It was found that the previously observed significant increase of P450 total content and hydroxyl radical levels after 7 days of ETBE administration, and 8-OHdG formation at day 14, accompanied by accumulation of CYP2B1/2B2, CYP3A1/3A2, CYP2C6, CYP2E1 and CYP1A1 and downregulation of DNA oxoguanine glycosylase 1, was preceded by induction of cell proliferation at day 3. Furthermore, we observed an increase in regenerative cell proliferation as a result of ETBE treatment at day 28, followed by induction of cell cycle arrest and apoptosis by day 14. These results indicated that short-term administration of ETBE led to a significant early increase in cell proliferation activity associated with induction of oxidative stress, and to a regenerative cell proliferation as an adaptive response, which could contribute to the hepatotumorigenicity of ETBE in rats.

    DOI: 10.1293/tox.2014-0056

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  • Modifying effects of 1,2-dichloropropane on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in male Syrian hamsters. Reviewed

    Gi M, Fujioka M, Yamano S, Shimomura E, Kanki M, Kawachi S, Tachibana H, Tatsumi K, Fang H, Ishii N, Kakehashi A, Wanibuchi H

    一般社団法人 日本毒性学会 The Journal of toxicological sciences   40 ( 5 )   647 - 56   2015( ISSN:0388-1350

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    Based on the findings of epidemiological studies in Japan that occupational exposure to 1,2-dichloropropane (1,2-DCP) was associated with increased cholangiocarcinomas, 1,2-DCP has recently been classified as being carcinogenic to humans (Group 1). However, the cholangiocarcinogenicity of 1,2-DCP has not been demonstrated experimentally, and it was negative for cholangiocarcinogenicity in rats and mice. The present study determined the effects of 1,2-DCP on N-nitrosobis(2-oxopropyl)amine (BOP)-induced cholangiocarcinogenesis in male hamsters. We found that 1,2-DCP did not enhance the development of BOP-induced atypical biliary hyperplasia and did not induce any lesions in liver bile duct when administered alone. Notably, 1,2-DCP had no effect on the proliferative activity of bile duct epithelial cells regardless of BOP-initiation. These results demonstrate that 1,2-DCP lacks promoting effects on BOP-induced cholangiocarcinogenesis and suggest the possibility that 1,2-DCP is not cholangiocarcinogenic to the hamster in the present model. In addition, 1,2-DCP also lacks promoting effects on pancreatic, lung, and renal carcinogenesis. As the occurrence of occupational cholangiocarcinomas in Japan might be attributed to exposure to multiple chemicals, the results of the present study indicate that it will be necessary to determine the cholangiocarcinogenic effects of concurrent exposure of 1,2-DCP and the other halogen solvents to which workers with cholangiocarcinomas were exposed.

    DOI: 10.2131/jts.40.647

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  • Valerian Inhibits Rat Hepatocarcinogenesis by Activating GABA(A) Receptor-Mediated Signaling Reviewed

    Kakehashi Anna, Kato Ayumi, Ishii Naomi, Wei Min, Morimura Keiichirou, Fukushima Shoji, Wanibuchi Hideki

    PLOS ONE   9 ( 11 )   e113610   2014.11( ISSN:1932-6203

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    DOI: 10.1371/journal.pone.0113610

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  • Comparative Proteomics Analysis of Gastric Cancer Stem Cells Reviewed

    Morisaki Tamami, Yashiro Masakazu, Kakehashi Anna, Inagaki Azusa, Kinoshita Haruhito, Fukuoka Tatsunari, Kasashima Hiroaki, Masuda Go, Sakurai Katsunobu, Kubo Naoshi, Muguruma Kazuya, Ohira Masaichi, Wanibuchi Hideki, Hirakawa Kosei

    PLOS ONE   9 ( 11 )   e110736   2014.11( ISSN:1932-6203

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    DOI: 10.1371/journal.pone.0110736

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  • Threshold of Genotoxic Carcinogens: Consideration from No-Effect Doses for Cancer-Related Markers in Chemical Carcinogenesis Reviewed

    Fukushima Shoji, Gi Min, Kakehashi Anna, Wanibuchi Hideki

    MUTAGENESIS   29 ( 6 )   554 - 554   2014.11( ISSN:0267-8357

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  • A Comparative Study of Clinicopathological Features Between Simple Bone Cysts of the Calcaneus and the Long Bone Reviewed

    Takada Jun, Hoshi Manabu, Oebisu Naoto, Ieguchi Makoto, Kakehashi Anna, Wanibuchi Hideki, Nakamura Hiroaki

    FOOT & ANKLE INTERNATIONAL   35 ( 4 )   374 - 382   2014.04( ISSN:1071-1007

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    DOI: 10.1177/1071100713519600

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  • Mode of action of ethyl tertiary-butyl ether hepatotumorigenicity in the rat: Evidence for a role of oxidative stress via activation of CAR, PXR and PPAR signaling pathways Reviewed

    Kakehashi Anna, Hagiwara Akihiro, Imai Norio, Nagano Kasuke, Nishimaki Fukumi, Banton Marcy, Wei Min, Fukushima Shoji, Wanibuchi Hideki

    TOXICOLOGY AND APPLIED PHARMACOLOGY   273 ( 2 )   390 - 400   2013.12( ISSN:0041-008X

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    DOI: 10.1016/j.taap.2013.09.016

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  • Novel medium-term carcinogenesis model for lung squamous cell carcinoma induced by N-nitrosotris-chloroethylurea in mice Reviewed

    Tago Yoshiyuki, Yamano Shotaro, Wei Min, Kakehashi Anna, Kitano Mitsuaki, Fujioka Masaki, Ishii Naomi, Wanibuchi Hideki

    CANCER SCIENCE   104 ( 12 )   1560 - 1566   2013.12( ISSN:1349-7006

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    DOI: 10.1111/cas.12289

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  • マウス膀胱発癌に及ぼすタバコ主流煙吸入による修飾作用の評価(Evaluation of the Modifying Effect of Inhalation of Mainstream Cigarette Smoke on Mouse Bladder Carcinogenesis) Reviewed

    Kato Minoru, Wei Min, Yamano Shotaro, Fujioka Masaki, Kakehashi Anna, Wanibuchi Hideki

    日本毒性病理学会 Journal of Toxicologic Pathology   26 ( 4 )   447 - 451   2013.12( ISSN:0914-9198

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    タバコ煙吸入曝露システムを用い、膀胱発癌に対するタバコ主流煙吸入の影響を評価した。6週齢雄性C57BLマウス96匹を対照群とタバコ煙曝露群に分け、8週間にわたり飲料水中に0.025%のN-butyl-N-(4-hydroxybutyl)nitrosamine(BBN)を添加して与えた。1週間のウオッシュアウト後、対照群には清浄な空気を、曝露群には300mg/m3のタバコ主流煙を22週間にわたり1週間に5日、1日2時間吸入曝露させた。膀胱腫瘍(乳頭腫および尿路上皮癌)の発生率は、統計的有意差には至らなかったが、対照群(15.8%)よりもタバコ煙曝露群(25.0%)で高かった。膀胱上皮におけるチトクロムP450(CYP)酵素および増殖細胞核抗原(PCNA)のmRNA発現レベルを評価したところ、cyp1a1発現はタバコ煙曝露群で有意に増加したが、cyp1a2、cyp1b1、cyp2a4、cyp2b10、cyp2e1、PCNAの発現には大きな影響を及ぼさなかった。以上から、22週間にわたるタバコ主流煙への限定的曝露によりcyp1a1発現の有意な増加が認められたが、膀胱腫瘍の増加は有意ではなく、膀胱発癌に対するタバコ煙の影響を明らかにするには、より長期の曝露が必要であることが示された。

  • Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats Reviewed

    Wei Min, Yamada Takanori, Yamano Shotaro, Kato Minoru, Kakehashi Anna, Fujioka Masaki, Tago Yoshiyuki, Kitano Mistuaki, Wanibuchi Hideki

    TOXICOLOGY AND APPLIED PHARMACOLOGY   273 ( 1 )   1 - 9   2013.11( ISSN:0041-008X

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    DOI: 10.1016/j.taap.2013.08.022

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  • Oxidative stress in the carcinogenicity of chemical carcinogens. Reviewed

    Kakehashi A, Wei M, Fukushima S, Wanibuchi H

    Cancers   5 ( 4 )   1332 - 54   2013.10

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    DOI: 10.3390/cancers5041332

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  • Oncomodulin is a novel early marker of urinary bladder carcinogenesis in F344 rats Reviewed

    Okumura M., Wei M., Yamano S., Fujioka M., Kakehashi A., Wanibuchi H.

    EUROPEAN JOURNAL OF CANCER   49   S198 - S199   2013.09( ISSN:0959-8049

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  • L-Leucine and L-isoleucine enhance growth of BBN-induced urothelial tumors in the rat bladder by modulating expression of amino acid transporters and tumorigenesis-associated genes Reviewed

    Xie Xiao-Li, Kakehashi Anna, Wei Min, Yamano Shotaro, Takeshita Masanori, Yunoki Takayuki, Wanibuchi Hideki

    FOOD AND CHEMICAL TOXICOLOGY   59   137 - 144   2013.09( ISSN:0278-6915

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    DOI: 10.1016/j.fct.2013.05.044

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  • Twenty-One Proteins Up-Regulated in Human H-ras Oncogene Transgenic Rat Pancreas Cancers are Up-Regulated in Human Pancreas Cancer Reviewed

    Yabushita Setsuko, Fukamachi Katsumi, Kikuchi Fumitake, Ozaki Masakazu, Miyata Kaori, Sukata Tokuo, Deguchi Yoshihito, Tanaka Hajime, Kakehashi Anna, Kawamura Satoshi, Uwagawa Satoshi, Wanibuchi Hideki, Suzui Masumi, Alexander David B., Tsuda Hiroyuki

    PANCREAS   42 ( 6 )   1034 - 1039   2013.08( ISSN:0885-3177

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  • Twenty-one proteins up-regulated in human H-ras oncogene transgenic rat pancreas cancers are up-regulated in human pancreas cancer. Reviewed

    Yabushita S, Fukamachi K, Kikuchi F, Ozaki M, Miyata K, Sukata T, Deguchi Y, Tanaka H, Kakehashi A, Kawamura S, Uwagawa S, Wanibuchi H, Suzui M, Alexander DB, Tsuda H

    Pancreas   42 ( 6 )   1034 - 9   2013.08( ISSN:0885-3177

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    DOI: 10.1097/MPA.0b013e3182883624

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  • Clinicopathological significance of combined analysis of cytokeratin19 expression and preoperative serum CYFRA21-1 levels in human lung squamous cell carcinoma. Reviewed

    Hanada S, Nishiyama N, Mizuguchi S, Yamano S, Kakehashi A, Wei M, Inoue H, Komatsu H, Chung K, Suehiro S, Wanibuchi H

    Osaka city medical journal   59 ( 1 )   35 - 44   2013.06( ISSN:0030-6096

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  • ヒト肺扁平上皮がんにおけるサイトケラチン19の発現と術前血清CYFRA21-1濃度の複合分析の臨床病理学的な意義(Clinicopathological Significance of Combined Analysis of Cytokeratin19 Expression and Preoperative Serum CYFRA21-1 Levels in Human Lung Squamous Cell Carcinoma) Reviewed

    Hanada Shoji, Nishiyama Noritoshi, Mizuguchi Shinjiro, Yamano Shotaro, Kakehashi Anna, Wei Min, Inoue Hidetoshi, Komatsu Hiroaki, Chung Kyukwang, Suehiro Shigefumi, Wanibuchi Hideki

    大阪市医学会 Osaka City Medical Journal   59 ( 1 )   35 - 44   2013.06( ISSN:0030-6096

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  • YT-4-1(YRA) 胃癌幹細胞関連蛋白の同定と臨床的意義(YT Young Researcher Award & Traveler's Grant,第113回日本外科学会定期学術集会) Reviewed

    森崎 珠実, 八代 正和, 渡邊 真央, 大北 仁裕, 福岡 達成, 長谷川 毅, 吉井 真美, 櫻井 克宣, 久保 尚士, 田中 浩明, 六車 一哉, 大平 雅一, 梯 アンナ, 鰐渕 英機, 平川 弘聖

    一般社団法人日本外科学会 日本外科学会雑誌   114 ( 2 )   2013.03( ISSN:18801129

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  • Complexin-2 (CPLX2) as a potential prognostic biomarker in human lung high grade neuroendocrine tumors Reviewed

    Komatsu Hiroaki, Kakehashi Anna, Nishiyama Noritoshi, Izumi Nobuhiro, Mizuguchi Shinjiro, Yamano Shotaro, Inoue Hidetoshi, Hanada Shoji, Chung Kyukwang, Wei Min, Suehiro Shigefumi, Wanibuchi Hideki

    CANCER BIOMARKERS   13 ( 3 )   171 - 180   2013( ISSN:1574-0153

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    DOI: 10.3233/CBM-130336

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  • Evaluation of the Modifying Effect of Inhalation of Mainstream Cigarette Smoke on Mouse Bladder Carcinogenesis Reviewed

    Kato Minoru, Wei Min, Yamano Shotaro, Fujioka Masaki, Kakehashi Anna, Wanibuchi Hideki

    日本毒性病理学会 JOURNAL OF TOXICOLOGIC PATHOLOGY   26 ( 4 )   447 - 451   2013( ISSN:0914-9198

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    Cigarette smoking is one of the major risk factors of bladder cancer in humans. To date, however, there is no experimental evidence for the effects of inhalation exposure to mainstream cigarette smoke on bladder carcinogenesis. The purpose of the present study was to evaluate the effect of inhalation of mainstream cigarette smoke on mouse bladder carcinogenesis using a cigarette smoke inhalation exposure system. Six-week-old male C57BL mice were administered 0.025% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for 8 weeks and then divided into 2 groups and exposed to 0 or 300 mg/m<sup>3</sup> wet total particulate matter mainstream cigarette smoke for 2 h per day, five times per week, for 22 weeks. The incidences of bladder tumors (papilloma and urothelial carcinoma) tended to increase in the cigarette smoke-exposed group (25.0%) compared with the controls (15.8%), albeit without a statistically significant difference. We also evaluated mRNA expression levels of cytochrome P450 (cyp) enzymes and proliferating cell nuclear antigen (PCNA) in the bladder epithelium. Expression of cyp1a1 was significantly increased in the cigarette smoke-exposed group. Cigarette smoke exposure did not have a significant effect on the expression of cyp1a2, cyp 1b1, cyp 2a4, cyp 2b10, cyp 2e1, or PCNA. In conclusion, limited exposure to mainstream cigarette smoke for 22 weeks, caused a significant increase in cyp1a1 expression. This increase coupled with the nonsignificant increase in bladder tumors suggests that a longer period of exposure is required to clarify the effects of cigarette smoke on bladder carcinogenesis.

    DOI: 10.1293/tox.2013-0039

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  • Myristoylated alanine-rich C-kinase substrate as a prognostic biomarker in human primary lung squamous cell carcinoma Reviewed

    Hanada Shoji, Kakehashi Anna, Nishiyama Noritoshi, Wei Min, Yamano Shotaro, Chung Kyukwang, Komatsu Hiroaki, Inoue Hidetoshi, Suehiro Shigefumi, Wanibuchi Hideki

    CANCER BIOMARKERS   13 ( 4 )   289 - 298   2013( ISSN:1574-0153

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    DOI: 10.3233/CBM-130354

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  • Dammar resin, a non-mutagen, induces oxidative stress and metabolic enzymes in the liver of gpt delta transgenic mouse which is different from a mutagen, 2-amino-3-methylimidazo[4,5-f]quinoline (vol 748, pg 29, 2012) Reviewed

    Xie Xiao-Li, Wei Min, Kakehashi Anna, Yamano Shotaro, Okabe Kyoko, Tajiri Masaki, Wanibuchi Hideki

    MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS   749 ( 1-2 )   105 - 105   2012.12( ISSN:1383-5718

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    DOI: 10.1016/j.mrgentox.2012.08.004

  • Threshold for Genotoxic Carcinogens : The Central Concern in Carcinogenic Risk Assessment Reviewed

    Fukushima Shoji, Wei Min, Kakehashi Anna, WANIBUCHI Hideki

    日本環境変異原学会 Genes and environment : the official journal of the Japanese Environmental Mutagen Society   34 ( 4 )   153 - 156   2012.11( ISSN:18807046

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    To verify scientifically whether the non-threshold concept of genotoxic carcinogenicity is valid, we examined the hepatocarcinogenicities at low doses of three genotoxic carcinogens: 2-amino-3, 8 dimethylimidazo[4,5-<i>f</i>]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-<i>f</i>]quinoline (IQ) and <i>N</i>-nitrosodiethylamine (DEN) using a medium-term rat hepatocarcinogenicity bioassay. We also examined alterations of molecular markers that cells typically acquire as they move through the initiation and promotion stages of carcinogenesis. We found that low doses of MeIQx induced formation of DNA-MeIQx adducts, somewhat higher doses caused elevation of oxidative DNA damage, at further higher doses gene mutations occurred; and the very highest dose of MeIQx induced formation of glutathione <i>S</i>-transferase placental form (GST-P) positive foci in the liver, a well-known preneoplastic lesion marker in rat hepatocarcinogenesis. Similarly, low doses of IQ and DEN had no effect on formation of GST-P positive foci in the rat liver. Furthermore, we demonstrated that concurrent treatment with combinations of sub-carcinogenic doses of MeIQx and DEN were not hepatocarcinogenic and the combined effects were neither additive nor synergistic. Moreover, concurrent treatment with low carcinogenic doses of these 2 carcinogens did not show additive or synergistic effects, and synergetic effects were observed only in rats co-administered high doses of those 2 carcinogens. These findings demonstrated the existence of no effect levels for these genotoxic hepatocarcinogens, and suggested that there is a threshold, at least a practical threshold, that should be considered when evaluating the risk of exposure to genotoxic carcinogens.<br>

    DOI: 10.3123/jemsge.34.153

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  • Long-term treatment with L-isoleucine or L-leucine in AIN-93G diet has promoting effects on rat bladder carcinogenesis Reviewed

    Xie Xiao-Li, Wei Min, Yunoki Takayuki, Kakehashi Anna, Yamano Shotaro, Kato Minoru, Wanibuchi Hideki

    FOOD AND CHEMICAL TOXICOLOGY   50 ( 11 )   3934 - 3940   2012.11( ISSN:0278-6915

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    DOI: 10.1016/j.fct.2012.07.063

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  • Dammar resin, a non-mutagen, inducts oxidative stress and metabolic enzymes in the liver of gpt delta transgenic mouse which is different from a mutagen, 2-amino-3-methylimidazo[4,5-f]quinoline Reviewed

    Xie Xiao-Li, Wei Min, Kakehashi Anna, Yamano Shotaro, Okabe Kyoko, Tajiri Masaki, Wanibuchi Hideki

    MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS   748 ( 1-2 )   29 - 35   2012.10( ISSN:1383-5718

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    DOI: 10.1016/j.mrgentox.2012.06.005

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  • ラットにおける低用量の2-amino-3,8-dimethylimidazo[4,5-f]quinoxalineとdiethylnitrosamineの混合による肝発癌性の欠如 遺伝毒性発癌物質に対する閾値の存在に関する示唆(Lack of Hepatocarcinogenicity of Combinations of Low Doses of 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline and Diethylnitrosamine in Rats: Indication for the Existence of a Threshold for Genotoxic Carcinogens) Reviewed

    Wei Min, Kakehashi Anna, Yamano Shotaro, Tamano Seiko, Shirai Tomoyuki, Wanibuchi Hideki, Fukushima Shoji

    日本毒性病理学会 Journal of Toxicologic Pathology   25 ( 3 )   209 - 214   2012.09( ISSN:0914-9198

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    ラットにて、2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline(MeIQx)とdiethylnitrosamine(DEN)の同時投与の肝発癌性を検討し、この組み合わせの無効果レベルが存在するかを調べた。実験1では、種々の用量のMeIQxで誘導の肝発癌に及ぼす発癌下用量のDEN同時投与を評価した。また、実験2では、発癌下、低発癌、高発癌用量のMeIQxとDENの組み合わせの肝発癌性を検討した。実験1で、DENはMeIQxの肝発癌性を増強せず、実験2では、発癌下用量の組み合わせでの肝発癌は見られず、発癌下用量のDENとMeIQxの組み合わせ効果は、相加的でも相乗的でもなかった。さらに低用量の組み合わせは、相加的・相乗的効果を示さず、高用量の同時投与で相乗効果が見られた。これらの結果は、この2つの肝発癌物質の組み合わせに無効果レベルのがあることを示した。

  • Methionine Sulfoxide Stimulates Hepatocarcinogenesis in Non-alcoholic Steatohepatitis (NASH) Mouse : Possible Role of Free Radical-mediated DNA Methylation Reviewed

    Kawai Kazuaki, Li Yun-Shan, Song Ming-Fen, OOTSUYAMA Yuko, KAKEHASHI Anna, WANIBUCHI Hideki, OOTSUYAMA Akira, NORIMURA Toshiyuki, KASAI Hiroshi

    日本環境変異原学会 Genes and environment : the official journal of the Japanese Environmental Mutagen Society   34 ( 3 )   123 - 128   2012.08( ISSN:18807046

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    We have reported the formation of 5-methylcytosine from cytosine <i>in vitro</i>, with methyl radicals generated from methionine sulfoxide (MetO). To confirm this reaction <i>in vivo</i>, MetO was added to the drinking water and administered to non-alcoholic steatohepatitis (NASH) mice, which develop hepatitis caused by endogenous oxidative stress. Histopathological examinations revealed incidences of hepatocellular carcinoma of 16.7% and 90% in the 0% and 3% MetO groups, respectively. Higher DNA methylation was detected in the promoter region of the <i>p16</i> gene isolated from the livers of MetO-treated mice. The higher incidence of liver tumors may be due to the methyl radical-mediated formation of 5-methylcytosine in DNA, which triggers epigenetic changes.<br>

    DOI: 10.3123/jemsge.34.123

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  • DDX39 acts as a suppressor of invasion for bladder cancer Reviewed

    Kato Minoru, Wei Min, Yamano Shotaro, Kakehashi Anna, Tamada Satoshi, Nakatani Tatsuya, Wanibuchi Hideki

    CANCER SCIENCE   103 ( 7 )   1363 - 1369   2012.07( ISSN:1349-7006

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    DOI: 10.1111/j.1349-7006.2012.02298.x

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  • AGR2 as a potential biomarker of human lung adenocarcinoma. Reviewed

    Chung K, Nishiyama N, Wanibuchi H, Yamano S, Hanada S, Wei M, Suehiro S, Kakehashi A

    Osaka city medical journal   58 ( 1 )   13 - 24   2012.06( ISSN:0030-6096

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  • AGR2 as a Potential Biomarker of Human Lung Adenocarcinoma Reviewed

    Chung Kyukwang, Nishiyama Noritoshi, Wanibuchi Hideki, Yamano Shotaro, Hanada Shoji, Wei Min, Suehiro Shigefumi, Kakehashi Anna

    大阪市立大学 Osaka City Medical journal   58 ( 1 )   13 - 24   2012.06( ISSN:00306096

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  • ヒト肺腺癌のバイオマーカーとなり得るAGR2(AGR2 as a Potential Biomarker of Human Lung Adenocarcinoma) Reviewed

    Chung Kyukwang, Nishiyama Noritoshi, Wanibuchi Hideki, Yamano Shotaro, Hanada Shoji, Wei Min, Suehiro Shigefumi, Kakehashi Anna

    大阪市医学会 Osaka City Medical Journal   58 ( 1 )   13 - 24   2012.06( ISSN:0030-6096

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    臨床使用と治療に有用な肺腺癌のバイオマーカーを同定するため、肺腺癌患者12名を対象に、液体クロマトグラフィー(LC)/タンデム質量分析(MS)を用いて過剰発現タンパク質を隣接の正常組織と比較した。12名中9名以上の肺腺癌患者で、177種のタンパク質が同定された。LC/タンデムMS、Ingenuity Pathway、免疫組織化学分析の結果に基づき、AGR2(anterior gradient homolog 2)が肺腺癌のバイオマーカーとして選別された。AGR2は肺腺癌患者の94%で陽性であった。負のAGR2発現は生存不良と関連した。AGR2はバイオマーカーとして臨床適用できる。

  • Proteome analysis of laser microdissected glomeruli from formalin-fixed paraffin-embedded kidneys of autopsies of diabetic patients: nephronectin is associated with the development of diabetic glomerulosclerosis Reviewed

    Nakatani Shinya, Wei Min, Ishimura Eiji, Kakehashi Anna, Mori Katsuhito, Nishizawa Yoshiki, Inaba Masaaki, Wanibuchi Hideki

    NEPHROLOGY DIALYSIS TRANSPLANTATION   27 ( 5 )   1889 - 1897   2012.05( ISSN:0931-0509

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    DOI: 10.1093/ndt/gfr682

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  • Comparison proteome analysis of scirrhous gastric carcinoma stem cell-like SP and hypoxia-resistant cell lines Reviewed

    Morisaki Tamami, Yashiro Masakazu, Kakehashi Anna, Okita Yoshihiro, Fukuoka Tatsunari, Aomatsu Naoki, Yoshii Mami, Hasegawa Tsuyoshi, Matsuoka Junko, Nagahara Hisashi, Kimura Kenjiro, Noda Eiji, Amano Ryosuke, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Yamada Nobuya, Maeda Kiyoshi, Nakata Bunzo, Ohira Masaichi, Wanibuchi Hideki, Hirakawa Kosei

    CANCER RESEARCH   72   2012.04( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2012-3380

  • Hormonally Active Doses of Isoflavone Aglycones Promote Mammary and Endometrial Carcinogenesis and Alter the Molecular Tumor Environment in Donryu Rats Reviewed

    Kakehashi Anna, Tago Yoshiyuki, Yoshida Midori, Sokuza Yui, Wei Min, Fukushima Shoji, Wanibuchi Hideki

    TOXICOLOGICAL SCIENCES   126 ( 1 )   39 - 51   2012.03( ISSN:1096-6080

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    DOI: 10.1093/toxsci/kfs016

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  • 2-Amino-3-Methylimidazo[4,5-f]Quinoline (IQ) Promotes Mouse Hepatocarcinogenesis by Activating Transforming Growth Factor-beta and Wnt/beta-Catenin Signaling Pathways Reviewed

    Xie Xiao-Li, Wei Min, Kakehashi Anna, Yamano Shotaro, Tajiri Masaki, Wanibuchi Hideki

    TOXICOLOGICAL SCIENCES   125 ( 2 )   392 - 400   2012.02( ISSN:1096-6080

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    DOI: 10.1093/toxsci/kfr314

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  • Lack of Hepatocarcinogenicity of Combinations of Low Doses of 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline and Diethylnitrosamine in Rats: Indication for the Existence of a Threshold for Genotoxic Carcinogens Reviewed

    Wei Min, Kakehashi Anna, Yamano Shotaro, Tamano Seiko, Shirai Tomoyuki, Wanibuchi Hideki, Fukushima Shoji

    日本毒性病理学会 JOURNAL OF TOXICOLOGIC PATHOLOGY   25 ( 3 )   209 - 214   2012( ISSN:0914-9198

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    The purposes of the present study were to evaluate the hepatocarcinogenicity of concurrent treatment of 2-amino-3,8-dimethylimidazo[4,5-<i>f</i>]quinoxaline (MeIQx) and diethylnitrosamine (DEN) in rats and to determine whether no effect levels of combinations of these two different structural categories of genotoxic hepatocarcinogens exist. Two 16-week rat hepatocarcinogenesis assays were performed using a total of 790 male F344 rats. In experiment 1, we evaluated the effects of concurrent treatment of a subcarcinogenic dose of DEN on rat hepatocarcinogenesis induced by various doses of MeIQx. In experiment 2, we determined hepatocarcinogenicities of combinations of MeIQx and DEN at subcarcinogenic doses, low carcinogenic doses and high carcinogenic doses. Quantitative analyses of glutathione <i>S</i>-transferase placental form (GST-P)-positive foci, a preneoplastic lesion of the liver in rats, revealed that concurrent treatment with subcarcinogenic doses of DEN did not enhance MeIQx-induced rat hepatocarcinogenicity. We also found that concurrent treatment with combinations of subcarcinogenic doses of DEN and MeIQx was not hepatocarcinogenic, indicating that the combined effects of subcarcinogenic doses of DEN and MeIQx were neither additive nor synergistic. Moreover, concurrent treatment with low carcinogenic doses of these 2 carcinogens did not show additive or synergistic effects. Synergetic effects were observed only in rats coadministered high carcinogenic doses of the 2 carcinogens. These results demonstrate the existence of no effect levels of combinations of these 2 genotoxic hepatocarcinogens, and provide new evidence supporting our idea that there is a threshold, at least a practical threshold, that should be considered when evaluating the risk of genotoxic carcinogens.

    DOI: 10.1293/tox.25.209

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  • Low-dose carcinogenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in rats: Evidence for the existence of no-effect levels and a mechanism involving p21(Cip/WAF1) Reviewed

    Wei Min, Kakehashi Anna, Yamano Shotaro, Fukushima Shoji, Wanibuchi Hideki

    CANCER RESEARCH   71   2011.04( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2011-5553

  • Enhanced Urinary Bladder, Liver and Colon Carcinogenesis in Zucker Diabetic Fatty Rats in a Multiorgan Carcinogenesis Bioassay : Evidence for Mechanisms Involving Activation of PI3K Signaling and Impairment of p53 on Urinary Bladder Carcinogenesis Reviewed

    ISHII Naomi, WEI Min, KAKEHASHI Anna, DOI Kenichiro, YAMANO Shotaro, INABA Masaaki, WANIBUCHI Hideki

    Journal of toxicologic pathology   24 ( 1 )   25 - 36   2011.03( ISSN:09149198

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  • Tumor-associated MUC5AC stimulates in vivo tumorigenicity of human pancreatic cancer Reviewed

    Hoshi Hirotaka, Sawada Tetsuji, Uchida Motoyuki, Saito Hikaru, Iijima Hiroko, Toda-Agetsuma Mikako, Wada Tsutomu, Yamazoe Sadaaki, Tanaka Hiroaki, Kimura Kenjiro, Kakehashi Anna, Wei Min, Hirakawa Kosei, Wanibuchi Hideki

    INTERNATIONAL JOURNAL OF ONCOLOGY   38 ( 3 )   619 - 627   2011.03( ISSN:1019-6439

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    DOI: 10.3892/ijo.2011.911

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  • Non-genotoxic mode of action and possible threshold for hepatocarcinogenicity of Kojic acid in F344 rats Reviewed

    Chusiri Yaowares, Wongpoomchai Rawiwan, Kakehashi Anna, Wei Min, Wanibuchi Hideki, Vinitketkumnuan Usanee, Fukushima Shoji

    FOOD AND CHEMICAL TOXICOLOGY   49 ( 2 )   471 - 476   2011.02( ISSN:0278-6915

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    DOI: 10.1016/j.fct.2010.11.027

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  • Mitochondrial Prohibitins and Septin 9 Are Implicated in the Onset of Rat Hepatocarcinogenesis Reviewed

    Kakehashi Anna, Ishii Naomi, Shibata Takeshi, Wei Min, Okazaki Etsuko, Tachibana Taro, Fukushima Shoji, Wanibuchi Hideki

    TOXICOLOGICAL SCIENCES   119 ( 1 )   61 - 72   2011.01( ISSN:1096-6080

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    DOI: 10.1093/toxsci/kfq307

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  • Targeted Proteomics of Isolated Glomeruli from the Kidneys of Diabetic Rats: Sorbin and SH3 Domain Containing 2 Is a Novel Protein Associated with Diabetic Nephropathy Reviewed

    Nakatani Shinya, Kakehashi Anna, Ishimura Eiji, Yamano Shotaro, Mori Katsuhito, Wei Min, Inaba Masaaki, Wanibuchi Hideki

    EXPERIMENTAL DIABETES RESEARCH   2011   979354   2011( ISSN:1687-5214

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    DOI: 10.1155/2011/979354

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  • Serum AGR2 as an early diagnostic and postoperative prognostic biomarker of human lung adenocarcinoma Reviewed

    Chung Kyukwang, Nishiyama Noritoshi, Yamano Shotaro, Komatsu Hiroaki, Hanada Shoji, Wei Min, Wanibuchi Hideki, Suehiro Shigefumi, Kakehashi Anna

    CANCER BIOMARKERS   10 ( 2 )   101 - 107   2011( ISSN:1574-0153

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    DOI: 10.3233/CBM-2012-0234

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  • Existence of a threshold for genotoxic carcinogens Reviewed

    WEI MIN, KAKEHASHI ANNA, FUKUSHIMA SHOJI, WANIBUCHI HIDEKI

    The Japanese Society of Toxicology, Annual Meeting of the Japanese Society of Toxicology   38 ( 0 )   184 - 184   2011

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    DOI: 10.14869/toxp.38.0.184.0

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  • Enhanced Urinary Bladder, Liver and Colon Carcinogenesis in Zucker Diabetic Fatty Rats in a Multiorgan Carcinogenesis Bioassay: Evidence for Mechanisms Involving Activation of PI3K Signaling and Impairment of p53 on Urinary Bladder Carcinogenesis Reviewed

    Ishii Naomi, Wei Min, Kakehashi Anna, Doi Kenichiro, Yamano Shotaro, Inaba Masaaki, Wanibuchi Hideki

    日本毒性病理学会 JOURNAL OF TOXICOLOGIC PATHOLOGY   24 ( 1 )   25 - 35   2011( ISSN:0914-9198

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    In the present study, modifying effects of diabetes on carcinogenesis induced in type 2 diabetes mellitus model Zucker diabetic fatty (ZDF) rats were investigated using a multiorgan carcinogenesis bioassay. Our results demonstrated enhancement of urinary bladder, colon and liver carcinogenesis in ZDF rats treated with five types of carcinogens (DMBDD). Elevated insulin and leptin and decreased adiponectin levels in the serum may be responsible for the high susceptibility of type 2 diabetes mellitus model rats to carcinogenesis in these organs. Possible mechanisms of increased susceptibility of diabetic rats to bladder carcinogenesis could be activation of the PI3K pathway and suppression of p53 in the urothelium in consequence of the above serum protein alterations.

    DOI: 10.1293/tox.24.25

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  • Evaluation of the Subchronic Toxicity of Dietary Administered Equisetum arvense in F344 Rats. Reviewed

    Tago Y, Wei M, Ishii N, Kakehashi A, Wanibuchi H

    日本毒性病理学会 Journal of toxicologic pathology   23 ( 4 )   245 - 51   2010.12( ISSN:0914-9198

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    <i>Equisetum arvense</i>, commonly known as the field horsetail, has potential as a new functional food ingredient. However, little information is available on its side effects, and the general toxicity of <i>Equisetum arvense</i> has yet to be examined in detail. In the present study, we evaluated the influence of administration in diet at doses of 0, 0.3, 1 and 3% for 13 weeks in male and female F344 rats. No toxicity was detected with reference to clinical signs, body weight, urinalysis, hematology and serum biochemistry data and organ weights. Microscopic examination revealed no histopathological lesions associated with treatment. In conclusion, the no-observed-adverse-effect level (NOAEL) for <i>Equisetum arvense</i> was determined to be greater than 3% in both sexes of F344 rat (males and females: >1.79 g/kg BW/day and >1.85 g/kg BW/day, respectively) under the conditions of the present study. <br>

    DOI: 10.1293/tox.23.245

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  • F344ラットにおける食餌中投与されたEquisetum arvenseの亜慢性毒性の評価(Evaluation of the Subchronic Toxicity of Dietary Administered Equisetum arvense in F344 Rats) Reviewed

    Tago Yoshiyuki, Wei Min, Ishii Naomi, Kakehashi Anna, Wanibuchi Hideki

    日本毒性病理学会 Journal of Toxicologic Pathology   23 ( 4 )   245 - 251   2010.12( ISSN:0914-9198

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    一般にスギナとして知られているE.arvenseは、新規の機能性食品材料になる可能性がある。しかし、その副作用に関する情報は殆んど利用できず、全身毒性に関しても詳しく調べられていない。F344雌雄ラットに、E.arvenseを食餌に0、0.3、1、3%混ぜて13週間与え、その毒性を検討した。臨床徴候、体重、尿検査データ、血液および血清生化学データ、臓器重量に関して、毒性は全く検出されなかった。顕微鏡検査で、処置関連組織病理学的病変は認められなかった。F344雌雄ラットにおいて、E.arvenseの無毒性量は3%以上である(雄では>1.79g/kg体重/日、雌では>1.85g/kg体重/日)。

  • Rat Monoclonal Antibody Specific for Septin 9 Reviewed

    Tachibana Taro, Okazaki Etsuko, Yoshimi Tomohiko, Azuma Masayuki, Kakehashi Anna, Wanibuchi Hideki

    HYBRIDOMA   29 ( 2 )   169 - 171   2010.04( ISSN:1554-0014

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    DOI: 10.1089/hyb.2009.0092

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  • Cytokeratin 8/18 as a new marker of mouse liver preneoplastic lesions Reviewed

    Kakehashi Anna, Kato Ayumi, Inoue Masayo, Ishii Naomi, Okazaki Etsuko, Wei Min, Tachibana Taro, Wanibuchi Hideki

    TOXICOLOGY AND APPLIED PHARMACOLOGY   242 ( 1 )   47 - 55   2010.01( ISSN:0041-008X

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    DOI: 10.1016/j.taap.2009.09.013

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  • Sensitive quantitative assay for point mutations in the rat H-ras gene based on single nucleotide primer extension Reviewed

    Yano Yoshihisa, Yano Tomohiro, Kinoshita Anna, Matoba Ai, Hasuma Tadayoshi, Wanibuchi Hideki, Morimura Keiichirou, Otani Shuzo, Fukushima Shoji

    EXPERIMENTAL AND THERAPEUTIC MEDICINE   1 ( 4 )   657 - 661   2010( ISSN:1792-0981

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    DOI: 10.3892/etm_00000103

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  • Evaluation of the Subchronic Toxicity of Dietary Administered Equisetum arvense in F344 Rats Reviewed

    Tago Yoshiyuki, Wei Min, Ishii Naomi, Kakehashi Anna, Wanibuchi Hideki

    JOURNAL OF TOXICOLOGIC PATHOLOGY   23 ( 4 )   245 - 251   2010( ISSN:0914-9198

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  • Characteristic upregulation of glucose-regulated protein 78 in an early lesion negative for hitherto established cytochemical markers in rat hepatocarcinogenesis. Reviewed

    Sukata T, Uwagawa S, Ozaki K, Sumida K, Kushida M, Kakehashi A, Wanibuchi H, Miyata K, Ogata K, Fukushima S

    日本毒性病理学会 Journal of toxicologic pathology   22 ( 4 )   281 - 8   2009.12( ISSN:0914-9198

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    Previously, we reported &alpha;<sub>2</sub>-macroglobulin (&alpha;<sub>2</sub>M) to be a novel marker characteristic of rat hepatocellular preneoplastic and neoplastic lesions negative for hitherto well-established markers. In the present study, we further examined other candidate markers with specificity for the same type of lesions. Glutathione <i>S</i>-transferase-placental form (GST-P)-negative hepatocellular altered foci (HAF) were generated using a two-stage (initiation and promotion) carcinogenesis protocol with N,N-diethylnitrosamine (DEN) and either Wy-14,643 or clofibrate, two peroxisome proliferators. Microarray analysis using total RNAs isolated from laser-microdissected GST-P-negative HAF (amphophilic cell foci) and adjacent normal tissues was conducted along with immunohistochemistry and real-time RT-PCR. Staining for glucose-regulated protein 78 (GRP78) was detected in GST-P-negative HAF and hepatocellular adenomas, and slightly increased GRP78 mRNA expression was observed in the lesions by real-time RT-PCR analysis. Thus, an early increase of GRP78 expression in hepatocarcinogenesis is likely a feature of the amphophilic subset of HAF. <br>

    DOI: 10.1293/tox.22.281

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  • Potassium Bromate Enhances N-Ethyl-N-Hydroxyethylnitrosamine-Induced Kidney Carcinogenesis Only at High Doses in Wistar Rats: Indication of the Existence of an Enhancement Threshold Reviewed

    Wei Min, Hamoud Al-Salmy, Yamaguchi Takashi, Kakehashi Anna, Marimura Keiichirou, Doi Kenichiro, Kushida Masahiko, Kitano Mitsuaki, Wanibuchi Hideki, Fukushima Shoji

    TOXICOLOGIC PATHOLOGY   37 ( 7 )   983 - 991   2009.12( ISSN:0192-6233

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    DOI: 10.1177/0192623309351720

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  • Urinary bladder carcinogenesis induced by chronic exposure to persistent low-dose ionizing radiation after Chernobyl accident Reviewed

    Romanenko Alina, Kakehashi Anna, Morimura Keiichirou, Wanibuchi Hideki, Wei Min, Vozianov Alexander, Fukushima Shoji

    CARCINOGENESIS   30 ( 11 )   1821 - 1831   2009.11( ISSN:0143-3334

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    DOI: 10.1093/carcin/bgp193

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  • Cytokeratin 8/18 overexpression and complex formation as an indicator of GST-P positive foci transformation into hepatocellular carcinomas Reviewed

    Kakehashi Anna, Inoue Masayo, Wei Min, Fukushima Shoji, Wanibuchi Hideki

    TOXICOLOGY AND APPLIED PHARMACOLOGY   238 ( 1 )   71 - 79   2009.07( ISSN:0041-008X

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    DOI: 10.1016/j.taap.2009.04.018

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  • Existence of a Threshold for the Genotoxic Carcinogens : Evidence from Mechanism-based Carcinogenicity Studies Reviewed

    Fukushima Shoji, Kakehashi Anna, Wei Min, WANIBUCHI Hideki

    日本環境変異原学会 Genes and environment : the official journal of the Japanese Environmental Mutagen Society   31 ( 2 )   33 - 36   2009.05( ISSN:18807046

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    The hepatocarcinogenicity of 2-amino-3,8-dimethylimidazo[4,5-<i>f</i>]quinoxaline (MeIQx), a carcinogen contained in fried meat and fish, was examined in the medium-term rat liver carcinogenicity bioassay. Induction of DNA-MeIQx adducts occurred with low doses of the chemical, followed by increasing doses by elevation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in DNA and <i>lacI</i> gene mutations, which might have been related to the initiation of carcinogenesis by MeIQx. Further elevation of the MeIQx dose was shown to cause the formation of glutathione <i>S</i>-transferase placental form (GST-P) positive foci in the liver, a well-known preneoplastic marker in rat hepatocarcinogenesis. In studies with <i>N</i>-nitrosocompounds such as <i>N</i>-nitrosodiethylamine and <i>N</i>-nitrosodimethylamine, no induction of GST-P positive foci was observed after their administration at low doses. When the carcinogenicity of a well-known colon carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-<i>b</i>]pyridine (PhIP) was examined, PhIP-DNA adduct formation was observed after treatment with low doses, while only high doses of the chemical were found to induce aberrant crypt foci (ACF), which are a surrogate marker of preneoplastic lesions in the colon. In experiments with potassium bromate, carcinogenicity, mutagenicity, and 8-OHdG formation in the rat kidney were observed only after administration at high dose. From these results, the genotoxic carcinogens were concluded to have a threshold, at least practical, with respect to their carcinogenicity.<br>

    DOI: 10.3123/jemsge.31.33

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  • Ethanol Does Not Promote MeIQx-initiated Rat Colon Carcinogenesis Based on Evidence from Analysis of a Colon Cancer Surrogate Marker. Reviewed

    Kushida M, Wanibuchi H, Wei M, Kakehashi A, Ozaki K, Sukata T, Miyata K, Ogata K, Uwagawa S, Fukushima S

    日本毒性病理学会 Journal of toxicologic pathology   22 ( 1 )   65 - 70   2009.03( ISSN:0914-9198

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    Epidemiological studies suggest that alcohol consumption increases the risk of developing colorectal cancer. However, the data are confounded by numerous cosegregating variables. To cast further light on the relationships between alcohol intake and colon cancer development, 21-day-old male F344/DuCrj rats were fed 200 ppm 2-amino-3,8-dimethylimidazo[4,5-<i>f</i>]quinoxaline (MeIQx) in their diet for 8 weeks and doses of 0, 0.1, 0.3, 1, 3, 10 and 20% of ethanol in their drinking water <i>ad libitum</i> for 16 weeks thereafter. The rats were sacrificed after 24 weeks of experiment, and aberrant crypt foci (ACF), surrogate lesions for colon cancer, were examined under a light microscope at low magnification. Ethanol was found not to affect the ACF formation at any dose compared with the initiated-controls. Furthermore, ethanol did not alter colon epithelial cell proliferation. These data, obtained by analysis of a colon cancer surrogate marker lesion, indicate that ethanol lacks promotion activity for MeIQx-initiated rat colon carcinogenesis. <br>

    DOI: 10.1293/tox.22.65

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  • Characteristic Upregulation of Glucose-Regulated Protein 78 in an Early Lesion Negative for Hitherto Established Cytochemical Markers in Rat Hepatocarcinogenesis Reviewed

    Sukata Tokuo, Uwagawa Satoshi, Ozaki Keisuke, Sumida Kayo, Kushida Masahiko, Kakehashi Anna, Wanibuchi Hideki, Miyata Kaori, Ogata Keiko, Fukushima Shoji

    JOURNAL OF TOXICOLOGIC PATHOLOGY   22 ( 4 )   281 - 288   2009( ISSN:0914-9198

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  • Ethanol Does Not Promote MeIQx-initiated Rat Colon Carcinogenesis Based on Evidence from Analysis of a Colon Cancer Surrogate Marker Reviewed

    Kushida Masahiko, Wanibuchi Hideki, Wei Min, Kakehashi Anna, Ozaki Keisuke, Sukata Tokuo, Miyata Kaori, Ogata Keiko, Uwagawa Satoshi, Fukushima Shoji

    JOURNAL OF TOXICOLOGIC PATHOLOGY   22 ( 1 )   65 - 70   2009( ISSN:0914-9198

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  • Are there thresholds for carcinogens carcinogenicity? Reviewed

    FUKUSHIMA Shoji, WEI Min, KAKEHASHI Anna, WANIBUCHI Hideki

    Japanese Society of Mycotoxicology, JSM Mycotoxins   58 ( 2 )   119 - 128   2008.07( ISSN:02851466

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    A food-derived, genotoxic hepatocarcinogen, 2-amino-3,8-dimethylimidazo[4,5-<i>f</i> ] quinoxaline (MeIQx) low-dose carcinogenicity was examined in the rat liver using a medium term bioassay for carcinogens. MeIQx was shown to form DNA adducts at very low doses, but did not induce 8-hydroxy-2&prime;-deoxyguanosine formations, lacI gene mutations or an initiation activity. Glutathione S-transferase placental form (GST-P)-positive foci which are preneoplastic lesions occurred at higher dose. Furthermore, <i>N</i>-nitroso compounds, such as <i>N</i>-nitrosodiethylamine and <i>N</i>-nitrosodimethylamine were found not to induce GST-P-positive foci in the rat liver at very low doses. A genotoxic colon carcinogen, 2-amino-1-methyl-6-phenolimidazo [4,5-<i>b</i>] pyridine (PhIP) induced PhIP-DNA adducts at very low dose with no-effect level and aberrant crypt foci as a surrogate marker of preneoplastic lesions appeared at relatively high doses.These results imply the existence of thresholds, at least practical ones for the carcinogenicities of these genotoxic carcinogens. A non-genotoxic carcinogen, phenobarbital showed hormetic phenomenon in rat hepatocarcinogenicity, indicating the real threshold for the carcinogenicity.

    DOI: 10.2520/myco.58.119

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  • Chemopreventive effects of a serratane-type triterpenoid, 3 alpha-methoxyserrat-14-en-21 beta-ol (PJ-1), against rat lung carcinogenesis Reviewed

    Yamaguchi Chiharu, Wanibuchi Hideki, Kakehashi Anna, Tanaka Reiko, Fukushima Shoji

    FOOD AND CHEMICAL TOXICOLOGY   46 ( 6 )   1882 - 1888   2008.06( ISSN:0278-6915

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    DOI: 10.1016/j.fct.2007.12.018

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  • 食品などに含まれる発がん物質に閾値が存在するのか Reviewed

    梯 アンナ

    食衛誌 49   2008

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  • Elevation of 8-hydroxydeoxyguanosine and cell proliferation via generation of oxidative stress by organic arsenicals contributes to their carcinogenicity in the rat liver and bladder Reviewed

    Kinoshita Anna, Wanibuchi Hideki, Wei Min, Yunokl Takayuki, Fukushima Shoji

    TOXICOLOGY AND APPLIED PHARMACOLOGY   221 ( 3 )   295 - 305   2007.06( ISSN:0041-008X

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    DOI: 10.1016/j.taap.2007.03.024

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  • Carcinogenicity of dimethylarsinic acid in Ogg1-deficient mice Reviewed

    Kinoshita Anna, Wanibuchi Hideki, Morimura Keiichirou, Wei Min, Nakae Dai, Arai Tsuyoshi, Minowa Osamu, Noda Tetsuo, Nishimura Susumu, Fukushima Shoji

    CANCER SCIENCE   98 ( 6 )   803 - 814   2007.06( ISSN:1347-9032

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    DOI: 10.1111/j.1349-7006.2007.00475.x

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  • Analysis of gene expression in different stages of MeIQx-induced rat hepatocarcinogenesis Reviewed

    Kang Jin Seok, Wanibuchi Hideki, Murai Takashi, Morimura Keiichirou, Kinoshita Anna, Fukushima Shoji

    ONCOLOGY REPORTS   17 ( 4 )   747 - 752   2007.04( ISSN:1021-335X

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  • Evaluation of the toxicity of mastic gum with 13 weeks dietary administration to F344 rats Reviewed

    Kang Jin Seok, Wanibuchi Hideki, Salim Elsayed I., Kinoshita Anna, Fukushima Shoji

    FOOD AND CHEMICAL TOXICOLOGY   45 ( 3 )   494 - 501   2007.03( ISSN:0278-6915

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    DOI: 10.1016/j.fct.2006.09.013

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  • Carcinogenicity of dimethylarsinic acid in Ogg1-deficient mice

    Cancer Science   98 ( 6 )   803 - 814   2007

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  • Elevation of 8-hydroxydeoxyguanosine and cell proliferation via generation of oxidative stress by organic arsenicals contributes to their carcinogenicity in the rat liver and bladder

    Toxicol Appl Pharmacol   221 ( 3 )   295 - 305   2007

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  • Upregulation of fibroblast growth factor receptor 3 and epidermal growth factor receptors, in association with Raf-1, in urothelial dysplasia and carcinoma in situ after the Chernobyl accident Reviewed

    Romanenko Alina M., Morimura Keiichirou, Kinoshita Anna, Wanibuchi Hideki, Takahashi Satoru, Zaparin Wadim K., Vinnichenko Wladimir I., Vozianov Alexander F., Fukushima Shoji

    CANCER SCIENCE   97 ( 11 )   1168 - 1174   2006.11( ISSN:1349-7006

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    DOI: 10.1111/j.1349-7006.2006.00309.x

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  • Hormesis in Carcinogenicity of Non-genotoxic Carcinogens Reviewed

    KINOSHITA Anna, WANIBUCHI Hideki, WEI Min, FUKUSHIMA Shoji

    日本毒性病理学会 Journal of toxicologic pathology   19 ( 3 )   111 - 122   2006.09( ISSN:0914-9198

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    Recently the idea of hormesis, a biphasic dose-response relationship in which a chemical exerts opposite effects dependent on the dose, has attracted interest in the field of carcinogenesis. With non-genotoxic agents there is considerable experimental evidence in support of hormesis and the present review highlights current knowledge of dose-response effects. In particular, several <i>in vivo</i> studies have provided support for the idea that non-genotoxic carcinogens may inhibit hepatocarcinogenesis at low doses. Here, we survey the examples and discuss possible mechanisms of hormesis with cytochrome P450 inducers, such as phenobarbital, 1,1-bis(<i>p</i>-chlorophenyl)-2,2,2-trichloroethane (DDT), &alpha;-benzene hexachloride (&alpha;-BHC), and other non-genotoxins. Epigenetic processes differentially can be affected by agents that impinge on oxidative stress, DNA repair, cell proliferation, apoptosis, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors, cause aberrant DNA methylation at the genomic level and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. Via multiple epigenetic lesions, non-genotoxic carcinogens can elicit a variety of changes contributing to cellular carcinogenesis.

    DOI: 10.1293/tox.19.111

    CiNii Article

  • Alpha-benzene hexachloride exerts hormesis in preneoplastic lesion formation of rat hepatocarcinogenesis with the possible role for hepatic detoxifying enzymes Reviewed

    Puatanachokchai Rawiwan, Morimura Keiichirou, Wanibuchi Hideki, Oka Mayuko, Kinoshita Anna, Mitsuru Fukui, Yamaguchi Shuji, Funae Yoshihiko, Fukushima Shoji

    CANCER LETTERS   240 ( 1 )   102 - 113   2006.08( ISSN:0304-3835

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.canlet.2005.09.006

    PubMed

  • N-acetylcysteine and S-methylcysteine inhibit MeIQx rat hepatocarcinogenesis in the post-initiation stage Reviewed

    Nishikawa-Ogawa M, Wanibuchi H, Morimura K, Kinoshita A, Nishikawa T, Hayashi S, Yano Y, Fukushima S

    CARCINOGENESIS   27 ( 5 )   982 - 988   2006.05( ISSN:0143-3334

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/carcin/bgi277

    PubMed

  • Lack of promoting effects of phenobarbital at low dose on diethylnitrosamine-induced hepatocarcinogenesis in TGF-alpha transgenic mice. Reviewed

    Puatanachokchai R, Kakuni M, Wanibuchi H, Kinoshita A, Kang JS, Salim EI, Morimura K, Tamano S, Merlino GT, Fukushima S

    Asian Pacific journal of cancer prevention : APJCP   7 ( 2 )   274 - 8   2006.04( ISSN:1513-7368

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    Publishing type:Research paper (scientific journal)  

    PubMed

  • A comparative study of the sub-chronic toxic effects of three organic arsenical compounds on the urothelium in F344 rats; gender-based differences in response Reviewed

    Shen J, Wanibuchi H, Waalkes MP, Salim EI, Kinoshita A, Yoshida K, Endo G, Fukushima S

    TOXICOLOGY AND APPLIED PHARMACOLOGY   210 ( 3 )   171 - 180   2006.02( ISSN:0041-008X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.taap.2005.04.018

    PubMed

  • Involvement of ubiquitination and sumoylation in bladder lesions induced by persistent long-term low dose ionizing radiation in humans Reviewed

    Romanenko AM, Kinoshita A, Wanibuchi H, Wei M, Zaparin WK, Vinnichenko WI, Vozianov AF, Fukushima S

    JOURNAL OF UROLOGY   175 ( 2 )   739 - 743   2006.02( ISSN:0022-5347

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/S0022-5347(05)00172-2

    PubMed

  • Aberrant expression of E-cadherin and beta-catenin in association with transforming growth factor-beta 1 in urinary bladder lesions in humans after the Chernobyl accident Reviewed

    Romanenko A, Morimura K, Kinoshita A, Wanibuchi H, Vozianov A, Fukushima S

    CANCER SCIENCE   97 ( 1 )   45 - 50   2006.01( ISSN:1347-9032

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1349-7006.2005.00131.x

    PubMed

  • Inhibition of rat urinary bladder carcinogenesis by the antiangiogenic drug TNP-470. Reviewed

    Wanibuchi H, Wei M, Salim EI, Kinoshita A, Morimura K, Sudo K, Fukushima S

    Asian Pacific journal of cancer prevention : APJCP   7 ( 1 )   101 - 7   2006.01( ISSN:1513-7368

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    Publishing type:Research paper (scientific journal)  

    PubMed

  • Effects of cessation of alcohol exposure on rat hepatocarcinogenesis. Reviewed

    Wanibuchi H, Zhang Y, Kinoshita A, Wei M, Kang JS, Fukushima S

    Asian Pacific journal of cancer prevention : APJCP   7 ( 1 )   122 - 6   2006.01( ISSN:1513-7368

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    Publishing type:Research paper (scientific journal)  

    PubMed

  • Upregulation of fibroblast growth factor receptor 3 and epidermal growth factor receptors, in association with Raf-1, in urothelial dysplasia and carcinoma in situ after the Chernobyl accident.

    97   1168 - 1174   2006

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    Publishing type:Research paper (scientific journal)  

  • Involvement of ubiquitination and sumoylation in bladder lesions induced by persistent long-term low dose ionizing radiation in humans.

    J. Urology   175 ( 2 )   739 - 743   2006

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    Publishing type:Research paper (scientific journal)  

  • Existence of no hepatocarcinogenic effect levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with or without coadministration with ethanol Reviewed

    Wanibuchi Hideki, Wei Min, Karim M. Rezaul, Morimura Keiichirou, Doi Kenichiro, Kinoshita Anna, Fukushima Shoji

    TOXICOLOGIC PATHOLOGY   34 ( 3 )   232 - 236   2006( ISSN:0192-6233

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1080/01926230600713632

    PubMed

  • Low dose DDT inhibition of hepatocarcinogenesis initiated by diethylnitrosamine in male rats: Possible mechanisms Reviewed

    Kushida M, Sukata T, Uwagawa S, Ozaki K, Kinoshita A, Wanibuchi H, Morimura K, Okuno Y, Fukushima S

    TOXICOLOGY AND APPLIED PHARMACOLOGY   208 ( 3 )   285 - 294   2005.11( ISSN:0041-008X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.taap.2005.03.018

    PubMed

  • Dose-dependence of promotion of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline-induced rat hepatocarcinogenesis by ethanol: Evidence for a threshold Reviewed

    Kushida M, Wanibuchi H, Morimura K, Kinoshita A, Kang JS, Puatanachokchai R, Wei M, Funae Y, Fukushima S

    CANCER SCIENCE   96 ( 11 )   747 - 757   2005.11( ISSN:1349-7006

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1349-7006.2005.00110.x

    PubMed

  • Hormesis and dose-response-mediated mechanisms in carcinogenesis: evidence for a threshold in carcinogenicity of non-genotoxic carcinogens Reviewed

    Fukushima S, Kinoshita A, Puatanachokchai R, Kushida M, Wanibuchi H, Morimura K

    CARCINOGENESIS   26 ( 11 )   1835 - 1845   2005.11( ISSN:0143-3334

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/carcin/bgi160

    PubMed

  • Current and emerging challenges in toxicopathology: carcinogenic threshold of phenobarbital and proof of arsenic carcinogenicity using rat medium-term bioassays for carcinogens. Reviewed

    Fukushima S, Morimura K, Wanibuchi H, Kinoshita A, Salim EI

    Toxicology and applied pharmacology   207 ( 2 Suppl )   225 - 9   2005.09( ISSN:0041-008X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.taap.2005.01.037

    PubMed

  • Lack of large intestinal carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine at low doses in rats initiated with azoxymethane Reviewed

    Doi K, Wanibuchi H, Salim EI, Morimura K, Kinoshita A, Kudoh S, Hirata K, Yoshikawa J, Fukushima S

    INTERNATIONAL JOURNAL OF CANCER   115 ( 6 )   870 - 878   2005.07( ISSN:0020-7136

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ijc.20960

    PubMed

  • Low dose DDT inhibition of hepatocarcinogenesis initiated by diethylnitrosamine in male rats: possible mechanisms

    208 ( 3 )   285 - 294   2005

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    Publishing type:Research paper (scientific journal)  

  • Alpha-benzene hexachloride exerts hormesis in preneoplastic lesion formation of rat hepatocarcinogenesis with the possible role for hepatic detoxifying enzymes.

    240 ( 1 )   102 - 113   2005

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    Publishing type:Research paper (scientific journal)  

  • Understanding arsenic carcinogenicity by the use of animal models Reviewed

    Wanibuchi H, Salim EI, Kinoshita A, Shen J, Wei M, Morimura K, Yoshida K, Kuroda K, Endo G, Fukushima S

    TOXICOLOGY AND APPLIED PHARMACOLOGY   198 ( 3 )   366 - 376   2004.08( ISSN:0041-008X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.taap.2003.10.032

  • Possible distinct molecular carcinogenic pathways for bladder cancer in Ukraine, before and after the Chernobyl disaster Reviewed

    Morimura K, Romanenko A, Min W, Salim EI, Kinoshita A, Wanibuchi H, Vozianov A, Fukushima S

    ONCOLOGY REPORTS   11 ( 4 )   881 - 886   2004.04( ISSN:1021-335X

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    Publishing type:Research paper (scientific journal)  

  • Lack of preventive efficacy of FK228, a histone deacetylase inhibitor, against N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder carcinogenesis in P53(+/-) and P53(+/+) mice Reviewed

    Wei M, Wanibuchi H, Morimura K, Salim EI, Moku M, Doi K, Mitsuhashi M, Masuda C, Shen J, Kinoshita A, Fukushima S

    ANTICANCER RESEARCH   24 ( 2B )   785 - 790   2004( ISSN:0250-7005

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    Publishing type:Research paper (scientific journal)  

  • Liver tumorigenicity of trimethylarsine oxide in male Fischer 344 rats-association with oxidative DNA damage and enhanced cell proliferation Reviewed

    Shen J, Wanibuchi H, Salim EI, Wei M, Kinoshita A, Yoshida K, Endo G, Fukushima S

    CARCINOGENESIS   24 ( 11 )   1827 - 1835   2003.11( ISSN:0143-3334

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/carcin/bgg143

  • Phenobarbital at low dose exerts hormesis in rat hepatocarcinogenesis by reducing oxidative DNA damage, altering cell proliferation, apoptosis and gene expression Reviewed

    Kinoshita A, Wanibuchi H, Morimura K, Wei M, Shen J, Imaoka S, Funae Y, Fukushima S

    CARCINOGENESIS   24 ( 8 )   1389 - 1399   2003.08( ISSN:0143-3334

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/carcin/bgg079

  • High susceptibility of p53 knockout mice to esophageal and urinary bladder carcinogenesis induced by N,N-dibutylnitrosamine Reviewed

    Nishikawa T, Salim EI, Morimura K, Kaneko M, Ogawa M, Kinoshita A, Osugi H, Kinoshita H, Fukushima S

    CANCER LETTERS   194 ( 1 )   45 - 54   2003.05( ISSN:0304-3835

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/S0304-3835(03)00057-0

  • Urinary bladder lesions induced by persistent chronic low-dose ionizing radiation Reviewed

    Romanenko A, Morimura K, Wanibuchi H, Wei M, Zaparin W, Vinnichenko W, Kinoshita A, Vozianov A, Fukushima S

    CANCER SCIENCE   94 ( 4 )   328 - 333   2003.04( ISSN:1347-9032

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    Publishing type:Research paper (scientific journal)  

  • Promoting effects of monomethylarsonic acid, dimethylarsinic acid and trimethylarsine oxide on induction of rat liver preneoplastic glutathione S-transferase placental form positive foci: A possible reactive oxygen species mechanism Reviewed

    Nishikawa T, Wanibuchi H, Ogawa M, Kinoshita A, Morimura K, Hiroi T, Funae Y, Kishida H, Nakae D, Fukushima S

    INTERNATIONAL JOURNAL OF CANCER   100 ( 2 )   136 - 139   2002.07( ISSN:0020-7136

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ijc.10471

  • Detailed low-dose study of 1,1-b is(p-chlorophenyl)-2,2,2-trichloroethane carcinogenesis suggests the possibility of a hormetic effect Reviewed

    Sukata T, Uwagawa S, Ozaki K, Ogawa M, Nishikawa T, Iwai S, Kinoshita A, Wanibuchi H, Imaoka S, Funae Y, Okuno Y, Fukushima S

    INTERNATIONAL JOURNAL OF CANCER   99 ( 1 )   112 - 118   2002.05( ISSN:0020-7136

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ijc.10312

  • Formation of 8-hydroxydeoxyguanosine and cell-cycle arrest in the rat liver via generation of oxidative stress by phenobarbital: association with expression profiles of p21(WAF1/Cip1), cyclin D1 and Ogg1 Reviewed

    Kinoshita A, Wanibuchi H, Imaoka S, Ogawa M, Masuda C, Morimura K, Funae Y, Fukushima S

    CARCINOGENESIS   23 ( 2 )   341 - 349   2002.02( ISSN:0143-3334

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    Publishing type:Research paper (scientific journal)  

  • Increased oxidative stress with gene alteration in urinary bladder urothelium after the Chernobyl accident Reviewed

    Romanenko A, Morimura K, Wanibuchi H, Salim EI, Kinoshita A, Kaneko M, Vozianov A, Fukushima S

    INTERNATIONAL JOURNAL OF CANCER   86 ( 6 )   790 - 798   2000.06( ISSN:0020-7136

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    Publishing type:Research paper (scientific journal)  

  • Biochemical markers of fetal brain developmental disturbances Reviewed

    Arutjunyan A.V., Pavlova N.G., Konstantinova N.N., Pavlenko A.V. (Kakehashi A.), Kashcheeva T.K., Kozina L.S., Kasheeva T.K.

    International Journal of Developmental Neuroscience   14   108 - 108   1996

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work  

  • Biochemical markers of brain development disorders Reviewed

    Arutjunyan A.V., Pavlova N.G., Konstantinova N.N., Pavlenko A.V. (Kakehashi A.), Kashcheeva T.K.,Lyzlova L.V., Kozina L.S., Rusina E.I., Mikhailov A.V., Shelaeva E.V.

    Neurochemistry   13 ( 3 )   187 - 193   1996

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    Publishing type:Research paper (scientific journal)   Kind of work:Joint Work  

▼display all

Books and Other Publications

  • Qualitative and Quantitative Assessments on Low-Dose Carcinogenicity of Genotoxic Hepatocarcinogens: Dose–Response for Key Events in Rat Hepatocarcinogenesis. In: Thresholds of Genotoxic Carcinogens, From Mechanisms to Regulation,

    ( Role: Joint author)

    2016.12 

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    Total pages:210   Responsible for pages:1–17  

  • Isoleucine, Leucine and Their Role in Experimental Models of Bladder Carcinogenesis. In: Branched Chain Amino Acids in Clinical Nutrition

    Wei M., Xie X-L., Yamano S., Kakehashi A., Wanibuchi H. ( Role: Joint author)

    2015 

  • Thresholds for Genotoxic Carcinogens: Evidence from Mechanism-Based Carcinogenicity Studies

    Fukushima S., Wei M., Kakehashi A., Wanibuchi H.( Role: Joint author)

    In: Cancer Risk Assessment: Chemical Carcinogenesis, Hazard Evaluation, and Risk Quantification, Chapter 8. Thresholds for Genotoxic Carcinogens: Evidence from Mechanism-Based Carcinogenicity Studies. Editors: Hsu C.-H. and Stedeford T. John Wiley & Sons, Inc., Hoboken, NJ, USA, 832 pages, pp. 207-222, 2010.  2010 

  • Neurochemistry: Cellular, Molecular and Clinical Aspects. BB-isoform of creatine kinase in amniotic fluid as a marker of brain development disorders.

    Arutjunyan A.V., Pavlova N.G., Konstantinova N.N., Pavlenko A.V.(Kakehashi A.), Kashcheeva T.K.,Lyzlova L.V., Kozina L.S., Rusina E.I., Mikhailov A.V., Shelaeva E.V.( Role: Joint author)

    1997 

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    Total pages:1226   Responsible for pages:457-460  

MISC

  • 1,4-ジオキサンはin vivo変異原性陽性である その変異原性および発がん性の定量解析 Reviewed

    魏 民, 藤岡 正喜, 梯 アンナ, 奥野 高裕, 増村 健一, 能美 健彦, 松本 道治, 大森 雅子, 鰐渕 英機, 福島 昭治

    大阪市医学会雑誌   69   32 - 32   2020.12( ISSN:0386-4103

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • NADPH oxidase阻害剤Apocyninは酸化ストレスの抑制を介しEHEN誘発ラット腎発がんを抑制する

    藤岡正喜, 魏民, 山野荘太郎, 河内聡子, 土井賢一郎, 石井真美, 梯アンナ, 鰐渕英機

    日本酸化ストレス学会学術集会プログラム・抄録集   69th   102‐103   2016.08

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    J-GLOBAL

  • 分子メカニズムからみた病変把握と免疫染色 病理組織のプロテオーム解析による病変マーカー開発 Reviewed

    鰐渕 英機, 梯 アンナ, 藤岡 正喜, 奥野 高裕, 魏 民

    日本組織細胞化学会 組織細胞化学   2016   175 - 189   2016.07

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  • 膀胱癌予防のためのリスク因子の同定と発癌機序の解明 Reviewed

    立花 大和, 魏 民, 梯 アンナ, 鰐渕 英機

    日本腎泌尿器疾患予防医学研究会 日本腎泌尿器疾患予防医学研究会誌   24 ( 1 )   24 - 28   2016.03( ISSN:1347-5010

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  • Mcl‐1蛋白を標的とする低分子抗がん物質の毒性と有効性の評価

    土井賢一郎, 鰐渕英機, 魏民, 梯アンナ, 石井真美, 山野荘太郎

    日本毒性病理学会講演要旨集   32nd   72 (JA),182 (EN)   2016

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    J-GLOBAL

  • 遺伝毒性発癌物質に対する閾値 発癌リスク評価を中心に(Threshold for Genotoxic Carcinogens: The Central Concern in Carcinogenic Risk Assessment) Reviewed

    Fukushima Shoji, Wei Min, Kakehashi Anna, Wanibuchi Hideki

    日本環境変異原学会 Genes and Environment   34 ( 4 )   153 - 156   2012.11( ISSN:1880-7046

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  • 非遺伝毒性肝発がん物質のラット肝臓における遺伝子発現解析

    神吉 将之, 魏 民, 梯 アンナ, 山野 荘太朗, 鰐渕 英機

    日本毒性病理学会講演要旨集   28回   77 - 77   2012.02

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  • 膀胱癌UPDATE(No.1) 目で診る膀胱癌 癌組織像を診る チェルノブイリ膀胱炎と膀胱癌 Reviewed

    鰐渕 英機, 梯 アンナ, 魏 民, 福島 昭治

    医学図書出版(株) 泌尿器外科   24 ( 11 )   1748 - 1753   2011.11( ISSN:0914-6180

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  • MicroRNA-125bはラット膀胱発がんの早期マーカーとして有用である(MircroRNA-125b is a potential early marker of rat urinary bladder carcinogenesis)

    魏 民, 梯 アンナ, 山野 荘太郎, 石井 真美, 北野 光昭, 鰐渕 英機

    日本癌学会総会記事   68回   146 - 147   2009.08( ISSN:0546-0476

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  • ラット膀胱発がん早期におけるイソロイシンおよびロイシンの修飾作用の検討(Effects of L-isoleucine and L-leucine at early stage of rat bladder carcinogenesis)

    謝 暁利, 山野 荘太郎, 陳 慶義, 梯 アンナ, 鰐渕 英機

    日本癌学会総会記事   68回   110 - 110   2009.08( ISSN:0546-0476

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  • ラット多臓器発がんにおける糖尿病の影響(Modifying effects of diabetes mellitus in a rat multi-organ carcinogenesis model)

    石井 真美, 魏 民, 梯 アンナ, 仲谷 慎也, 森 聖, 鰐渕 英機

    日本癌学会総会記事   68回   118 - 118   2009.08( ISSN:0546-0476

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  • QSTAR Elite LC-MS/MSを用いたマウス肺腫瘍におけるプロテオーム解析(The proteome analysis of mice lung tumors by QSTAR Elite LC-MS/MS)

    山野 荘太郎, 梯 アンナ, 魏 民, 多胡 善幸, 陳 慶義, 鰐渕 英機

    日本癌学会総会記事   68回   121 - 121   2009.08( ISSN:0546-0476

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  • 膀胱発がん物質の早期検出マーカーの検討

    魏 民, 梯 アンナ, 福島 昭治, 鰐渕 英機

    日本病理学会会誌   98 ( 1 )   226 - 226   2009.03( ISSN:0300-9181

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  • マウス肝発がんにおけるプロテオーム及びバイオマーカーの検討

    梯 アンナ, 石井 真美, 魏 民, 鰐渕 英機

    日本病理学会会誌   98 ( 1 )   357 - 357   2009.03( ISSN:0300-9181

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  • ZDFラットを用いた糖尿病の発がんに及ぼす影響

    石井 真美, 魏 民, 梯 アンナ, 多胡 善幸, 鰐渕 英機

    日本病理学会会誌   98 ( 1 )   320 - 320   2009.03( ISSN:0300-9181

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  • 食品などに含まれる発がん物質に閾値が存在するのか

    福島 昭治, 梯 アンナ, 魏 民, 鰐渕 英機

    食品衛生学雑誌   49 ( 5 )   J - 314   2008.10( ISSN:0015-6426

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  • 大豆イソフラボンのラット乳腺および子宮発がんに対する修飾作用(Modifying effects of soybean isoflavone on mammary gland and uterus carcinogenesis in Donryu rats)

    多胡 善幸, 梯 アンナ, 北野 光昭, 山野 荘太郎, 大西 真里子, 鰐渕 英機

    日本癌学会総会記事   67回   181 - 181   2008.09( ISSN:0546-0476

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  • ラット肝発がんにおけるGST-P陽性細胞巣のプロテオーム及びバイオマーカーの検討(Proteomics of GST-P positive foci in rat hepatocarcinogenesis: Analysis of potential biomarkers)

    梯 アンナ, 今中 麻幸代, 魏 民, 大西 真里子, 福島 昭治, 鰐渕 英機

    日本癌学会総会記事   67回   122 - 122   2008.09( ISSN:0546-0476

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  • マウスにおける肝前がん病変マーカーの検索(Analysis of novel protein biomarkers in mice hepatocarcinogenesis)

    植松 真美, 梯 アンナ, 今中 麻幸代, 魏 民, 森 聖, 鰐渕 英機

    日本癌学会総会記事   67回   122 - 122   2008.09( ISSN:0546-0476

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  • Oncomodulinはラット膀胱発がんの早期マーカーとして有用である(Oncomodulin is a potential early marker of urinary bladder carcinogenesis in rats)

    魏 民, 森村 圭一朗, 梯 アンナ, 土井 賢一郎, 福島 昭治, 鰐渕 英機

    日本癌学会総会記事   67回   118 - 118   2008.09( ISSN:0546-0476

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  • Ogg1遺伝子欠損マウスにおける多臓器発がんの検討

    植松 真美, 梯 アンナ, 魏 民, 北野 光昭, 福島 昭治, 鰐渕 英機

    日本病理学会会誌   97 ( 1 )   368 - 368   2008.03( ISSN:0300-9181

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  • チェルノブイリ原発事故後の長期低用量放射線暴露による膀胱がんの発生

    梯 アンナ, 森村 圭一朗, 猪上 麻幸代, 魏 民, 福島 昭治, 鰐渕 英機

    日本病理学会会誌   97 ( 1 )   343 - 343   2008.03( ISSN:0300-9181

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  • ジフェニルアルシン酸のラット肝発がんプロモーション作用

    魏 民, 梯 アンナ, 土井 賢一郎, 森村 圭一朗, 福島 昭治, 鰐渕 英機

    日本病理学会会誌   97 ( 1 )   267 - 267   2008.03( ISSN:0300-9181

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  • 大豆イソフラボンのラット乳腺発がんおよび子宮に対する修飾作用

    多胡 善幸, 梯 アンナ, 今中 麻幸代, 魏 民, 森村 圭一朗, 林 修次, 鰐渕 英機

    日本毒性病理学会講演要旨集   24回   94 - 94   2008.02

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  • ラット膀胱発癌におけるロイシン、イソロイシンの修飾作用の検討

    山野 荘太郎, 柚木 孝之, 梯 アンナ, 森 聖, 福島 昭治, 鰐渕 英機

    日本毒性病理学会講演要旨集   24回   92 - 92   2008.02

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  • ラット肝発がんにおけるGST-P陽性細胞巣のプロテオームおよびバイオマーカー解析

    梯 アンナ, 魏 民, 森村 圭一朗, 串田 昌彦, 福島 昭治, 鰐渕 英機

    日本毒性病理学会講演要旨集   24回   79 - 79   2008.02

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  • マウス肝発がんにおける前がん病変マーカーの検索および機序解析

    加藤 あゆみ, 梯 アンナ, 魏 民, 多胡 善幸, 山野 荘太郎, 村井 隆, 鰐渕 英機

    日本毒性病理学会講演要旨集   24回   79 - 79   2008.02

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  • 【尿路系腫瘍をめぐる諸問題】 尿路上皮癌の組織分類 新WHO分類との対比

    鰐渕 英機, 魏 民, 梯 アンナ, 福島 昭治

    病理と臨床   26 ( 2 )   124 - 129   2008.02( ISSN:0287-3745

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  • OGG1遺伝子欠損マウスにおける多臓器発がんの検討

    植松 真美, 梯 アンナ, 魏 民, 森村 圭一朗, 北野 光昭, 福島 昭治, 鰐渕 英機

    日本毒性病理学会講演要旨集   24回   84 - 84   2008.02

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  • 臭素酸カリウムのラット腎臓における変異原性と発がん性の閾値の存在

    魏 民, 森村 圭一朗, 梯 アンナ, 串田 昌彦, 當真 香織, 鰐渕 英機, 福島 昭治

    日本毒性病理学会講演要旨集   24回   88 - 88   2008.02

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  • 【毒性病理学の最近の話題】 慢性ヒ素汚染 がんと烏脚病

    鰐渕 英機, 魏 民, 梯 アンナ, 福島 昭治

    病理と臨床   25 ( 8 )   780 - 785   2007.08( ISSN:0287-3745

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  • ラット肝中期発癌性試験法を用いたマスティックの発癌性評価(Carcinogenic Effect of Mastic on Rat Liver Median-term Bioassay)

    土井 賢一郎, 魏 民, 梯 アンナ, 今中 麻幸代, 當眞 香織, 鰐渕 英機

    日本癌学会総会記事   66回   47 - 47   2007.08( ISSN:0546-0476

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  • ラットを用いたプロポリスの発がん性試験(Lack of carcinogenicitv of Propolis in rats)

    鰐渕 英機, 梯 アンナ, 今中 麻幸代, 當眞 香織, 魏 民, 森村 圭一朗, 福島 昭治

    日本癌学会総会記事   66回   355 - 355   2007.08( ISSN:0546-0476

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  • マウス肝発がんにおける前がん病変マーカーの検索(Cytokeratin 8/18 as a novel preneoplastic lesion marker regarding hepatocarcinogenesis in mice)

    加藤 あゆみ, 梯 アンナ, 魏 民, 當眞 香織, 植松 真美, 鰐渕 英機

    日本癌学会総会記事   66回   111 - 111   2007.08( ISSN:0546-0476

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Presentations

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Outline of collaborative research (seeds)

  • Biochemical and molecular-biological analysis of carcinogenesis mechanisms

    2005-

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    Request for collaborative research:Universities etc. Research institutes

    Type of research exchange:Contract research

    Core knowledge, technology, information etc:Chemical carcinogenesis, molecular and toxicologic pathology, biochemistry

    Study on mechanisms of chemical carcinogenesis:searching for biomarkers by analysing proteomics of preneplastic and cancer lesions

  • Investigation of markers and mechanisms of virus and MASH-associated liver cancer

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    Request for collaborative research:Universities etc. Research institutes

    Type of research exchange:Joint research

  • Hormesis and dose response-mediated mechanisms in carcinogenesis

    1999-

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    Request for collaborative research:Universities etc. Research institutes

    Type of research exchange:Contract research, Joint research, Lecture

    Application fields / methods etc:Recently the idea of hormesis, a biphasic dose-response relationship in which a chemical exerts opposite effects dependent on the dose, has attracted interest in the field of carcinogenesis.

    Core knowledge, technology, information etc:chemical carcinogenesis, cancer risk assessment, molecular,toxicologic pathology

    Recently the idea of hormesis has attracted interest in the field of carcinogenesis.

  • Elucidation of novel early biomarkers and carcinogenic mechanisms of invasive pancreatic ductal carcinoma

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    Request for collaborative research:Universities etc. Research institutes

    Type of research exchange:Joint research

Grant-in-Aid for Scientific Research

  • Elucidation of diagnostic markers for early detection of invasive pancreatic ductal carcinoma and development of new organoid culture model

    Grant-in-Aid for Scientific Research(C)  2025

  • Elucidation of diagnostic markers for early detection of invasive pancreatic ductal carcinoma and development of new organoid culture model

    Grant-in-Aid for Scientific Research(C)  2024

  • Elucidation of diagnostic markers for early detection of invasive pancreatic ductal carcinoma and development of new organoid culture model

    Grant-in-Aid for Scientific Research(C)  2023.04

  • Investigation of markers and mechanisms of NASH-associated liver cancer

    Grant-in-Aid for Scientific Research(C)  2017.04

  • Pinpoint targeting of hepatocellular carcinoma for new therapeutic application

    Grant-in-Aid for Scientific Research(C)  2012.04

  • Proteomics of Human Pancreatic Ductal Adenocarcinoma using FFPE Sections

    Grant-in-Aid for Scientific Research(C)  2011.04

  • Proteome analysis of isolated glomeruli of diabetic nephropathy

    Grant-in-Aid for Scientific Research(C)  2010.04

  • The strategic proteome analysis for the development of early diagnosis and therapeutic target of primary lung adenocarcinoma

    Grant-in-Aid for Scientific Research(C)  2010.04

  • Investigation of hepatocarcinogenesis mechanisms : targeted proteomics of liver preneoplastic lesions and tumors

    Grant-in-Aid for Young Scientists(B)  2007.04

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Contract research

  • ラットにおける2‐エトキシ‐2‐メチルプロパンの肝臓発がん性のメカニズム解析試験‐透過電子顕微鏡解析

    株式会社DIMS医科学研究所  2012.04

  • ラットにおける2‐エトキシ‐2‐メチルプロパンの肝臓発がん性のメカニズム解析試験における分子生物学的検索

    株式会社DIMS医科学研究所  2011.04

Other subsidies, etc.

  • Novel biomarkers and mechanisms in NASH-related hepatocarcinogenesis

    2016

  • Hormesis in rat hepatocarcinogenesis

    2002