Updated on 2022/04/08

写真a

 
ISHIKAWA, Tetsuya
 
Organization
Graduate School of Medicine Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Health Sciences
Title
Professor
Contact information
メールアドレス

Degree 1

  1. Doctor of Medicine ( 1996.3   Nagoya University ) 

Research Interests 4

  1. Hepatology

  2. Regenerative Medicine

  3. Immunology

  4. Virology

Research Areas 1

  1. Life Science / Gastroenterology  / Digestive Organs Internal Medicine

Current Research Project and SDGs 5

  1. B型慢性肝炎に対する新規経口TLR-7アゴニスト(SA-5)を基盤とした治療法の開発と医師主導FIH試験の体制整備

  2. ウイルス・発がんを統合的に制御する新規B型肝炎分子免疫治療の開発

  3. 細胞移植をベースとする肝再生治療モデルの確立と免疫拒絶回避のための新規治療の 開発

  4. 新規HBV感染症モデルを用いた治療的ワクチン療法の開発

  5. HBs抗原陰性化に関わるB型肝炎ウイルス変異と腸内細菌叢が及ぼす免疫応答の解明

Research History 10

  1. Nagoya University   Omics Health Sciences, Department of Integrated Health Sciences,   Professor

    2020.4

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    Country:Japan

  2. Nagoya University Graduate School of Medicine   Lab. of Biomolecular Sciences, Div. of Omics Health Sciences, Dept. of Integrated Health Sciences   Professor   MD, PhD

    2020.4

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    Country:Japan

  3. Nagoya University   Institute of Nano-Life-Systems, Institutes of Innovation for Future Society

    2018.10

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    Country:Japan

  4. Nagoya University Graduate School of Medicine   Department of Radiological & Medical Laboratory Sciences   Professor

    2012.4 - 2020.3

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    Country:Japan

  5. Professor, Nagoya University School of Health Sciences   Professor

    2010.4

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    Country:Japan

  6. Chairman, Cancer Immunotherapy Center, Nagoya Kyoritsu Hospital

    2007.11 - 2010.3

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    Country:Japan

  7. Associate Professor, Aichi Medical University

    2006.11 - 2007.10

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    Country:Japan

  8. Lecturer, Aichi Medical University

    1998.4 - 2006.11

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    Country:Japan

  9. Research Associate, Aichi Medical University

    1996.7 - 1998.3

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    Country:Japan

  10. Research Associate, The Scripps Research Institute

    1993.1 - 1995.5

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Education 2

  1. Nagoya University   Graduate School, Division of Medicine   Internal Medicine Ⅲ

    1989.4 - 1995.8

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    Country: Japan

  2. Nagoya University   Faculty of Medicine

    1979.4 - 1985.3

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    Country: Japan

Professional Memberships 13

  1. The Japan Society of Hepatology   Councillor

    2008.4

  2. The Japanese Society of Gastroenterology   Councillor

    1987.6

  3. The Japanese Society of Internal Medicine

    1988.6

  4. The Japanese Society of Inflammation and Regeneration

    2016.4

  5. 日本再生医療学会

    2014.1

  6. Japanese Society of Immunology

    1996.6

  7. The Japanese Society for Virology

    2002.1

  8. Japanese Cancer Association

    2008.10

  9. Japan Society of Clinical Oncology

    2008.10

  10. Japan Association of Cancer Immunology

    2008.2

  11. The Japanese Society for the Research of Hepatic Cells

    2016.5

  12. Asian Pacific Association for the Study of the Liver

    2015.9

  13. Japanese Society of Laboratory Medicine

    2012.7

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Committee Memberships 6

  1. 名古屋大学大学院医学系研究科総合保健学専攻   副学科長  

    2018.4   

  2. 名古屋大学大学院医学系研究科総合保健学専攻   予算委員会 委員長  

    2018.4   

  3. 名古屋大学大学院医学系研究科総合保健学専攻   整備計画委員会保健学部会 委員長  

    2018.4   

  4. 名古屋大学   キャンパスマネジメント本部会議 委員  

    2018.4   

  5. 名古屋大学   防災推進本部会議 委員  

    2018.4   

  6. 名古屋大学   極低温実験室運営委員会  

    2012.4   

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Awards 3

  1. 研究助成費

    1999.1   国際科学振興財団  

    石川哲也

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    Award type:Award from publisher, newspaper, foundation, etc.  Country:Japan

  2. 日東学術振興財団海外派遣助成費

    1999.1   日東工業  

    石川哲也

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    Award type:Award from publisher, newspaper, foundation, etc.  Country:Japan

  3. 愛知医科大学研究奨励賞

    1997.10   愛知医科大学  

    石川哲也

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    Country:Japan

 

Papers 212

  1. All-atom molecular dynamics study of hepatitis B virus containing pregenome RNA in solution. Reviewed

    Fujimoto K, Yamaguchi Y, Urano R, Shinoda W, Ishikawa T, Omagari K, Tanaka Y, Nakagawa A, Okazaki S

    The Journal of chemical physics   Vol. 155 ( 14 ) page: 145101   2021.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Chemical Physics  

    Immature hepatitis B virus (HBV) captures nucleotides in its capsid for reverse transcription. The nucleotides and nucleotide analog drugs, which are triphosphorylated and negatively charged in the cell, approach the capsid via diffusion and are absorbed into it. In this study, we performed a long-time molecular dynamics calculation of the entire HBV capsid containing pregenome RNA to investigate the interactions between the capsid and negatively charged substances. Electric field analysis demonstrated that negatively charged substances can approach the HBV capsid by thermal motion, avoiding spikes. The substances then migrate all over the floor of the HBV capsid. Finally, they find pores through which they can pass through the HBV capsid shell. Free energy profiles were calculated along these pores for small ions to understand their permeability through the pores. Anions (Cl−) showed higher free energy barriers than cations (Na+ and K+) through all pores, and the permeation rate of Cl− was eight times slower than that of K+ or Na+. Furthermore, the ions were more stable in the capsid than in the bulk water. Thus, the HBV capsid exerts ion selectivity for uptake and provides an environment for ions, such as nucleotides and nucleotide analog drugs, to be stabilized within the capsid.

    DOI: 10.1063/5.0065765

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  2. Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis. Reviewed

    Muto H, Ito T, Tanaka T, Yokoyama S, Yamamoto K, Imai N, Ishizu Y, Maeda K, Honda T, Ishikawa T, Kato A, Ohshiro T, Kano F, Yamamoto A, Sakai K, Hibi H, Ishigami M, Fujishiro M

    Scientific reports   Vol. 11 ( 1 ) page: 18778   2021.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Scientific Reports  

    Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.

    DOI: 10.1038/s41598-021-98254-8

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  3. Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional Cure. Invited Reviewed

    Honda T, Yamada N, Murayama A, Shiina M, Aly HH, Kato A, Ito T, Ishizu Y, Kuzuya T, Ishigami M, Murakami Y, Tanaka T, Moriishi K, Nishitsuji H, Shimotohno K, Ishikawa T, Fujishiro M, Muramatsu M, Wakita T, Kato T

    Cellular and molecular gastroenterology and hepatology   Vol. 12 ( 5 ) page: 1583 - 1598   2021.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Cellular and Molecular Gastroenterology and Hepatology  

    Background & Aims: To provide an adequate treatment strategy for chronic hepatitis B, it is essential to know which patients are expected to have a good prognosis and which patients do not require therapeutic intervention. Previously, we identified the substitution of isoleucine to leucine at amino acid 97 (I97L) in the hepatitis B core region as a key predictor among patients with stable hepatitis. In this study, we attempted to identify the point at which I97L affects the hepatitis B virus (HBV) life cycle and to elucidate the underlying mechanisms governing the stabilization of hepatitis. Methods: To confirm the clinical features of I97L, we used a cohort of hepatitis B e antigen–negative patients with chronic hepatitis B infected with HBV-I97 wild-type (wt) or HBV-I97L. The effects of I97L on viral characteristics were evaluated by in vitro HBV production and infection systems with the HBV reporter virus and cell culture-generated HBV. Results: The ratios of reduction in hepatitis B surface antigen and HBV DNA were higher in patients with HBV-I97L than in those with HBV-I97wt. HBV-I97L exhibited lower infectivity than HBV-I97wt in both infection systems with reporter HBV and cell culture-generated HBV. HBV-I97L virions exhibiting low infectivity primarily contained a single-stranded HBV genome. The lower efficiency of cccDNA synthesis was demonstrated after infection of HBV-I97L or transfection of the molecular clone of HBV-I97L. Conclusions: The I97L substitution reduces the level of cccDNA through the generation of immature virions with single-stranded genomes. This I97L-associated low efficiency of cccDNA synthesis may be involved in the stabilization of hepatitis.

    DOI: 10.1016/j.jcmgh.2021.07.013

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  4. Interferon signaling suppresses the unfolded protein response and induces cell death in hepatocytes accumulating hepatitis B surface antigen. Reviewed International coauthorship International journal

    Ian Baudi, Masanori Isogawa, Federica Moalli, Masaya Onishi, Keigo Kawashima, Yuji Ishida, Chise Tateno, Yusuke Sato, Hideyoshi Harashima, Hiroyasu Ito, Tetsuya Ishikawa, Takaji Wakita, Matteo Iannacone, Yasuhito Tanaka

    PLoS pathogens   Vol. 17 ( 5 ) page: e1009228   2021.5

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    Virus infection, such as hepatitis B virus (HBV), occasionally causes endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is counteractive machinery to ER stress, and the failure of UPR to cope with ER stress results in cell death. Mechanisms that regulate the balance between ER stress and UPR are poorly understood. Type 1 and type 2 interferons have been implicated in hepatic flares during chronic HBV infection. Here, we examined the interplay between ER stress, UPR, and IFNs using transgenic mice that express hepatitis B surface antigen (HBsAg) (HBs-Tg mice) and humanized-liver chimeric mice infected with HBV. IFNα causes severe and moderate liver injury in HBs-Tg mice and HBV infected chimeric mice, respectively. The degree of liver injury is directly correlated with HBsAg levels in the liver, and reduction of HBsAg in the transgenic mice alleviates IFNα mediated liver injury. Analyses of total gene expression and UPR biomarkers' protein expression in the liver revealed that UPR is induced in HBs-Tg mice and HBV infected chimeric mice, indicating that HBsAg accumulation causes ER stress. Notably, IFNα administration transiently suppressed UPR biomarkers before liver injury without affecting intrahepatic HBsAg levels. Furthermore, UPR upregulation by glucose-regulated protein 78 (GRP78) suppression or low dose tunicamycin alleviated IFNα mediated liver injury. These results suggest that IFNα induces ER stress-associated cell death by reducing UPR. IFNγ uses the same mechanism to exert cytotoxicity to HBsAg accumulating hepatocytes. Collectively, our data reveal a previously unknown mechanism of IFN-mediated cell death. This study also identifies UPR as a potential target for regulating ER stress-associated cell death.

    DOI: 10.1371/journal.ppat.1009228

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  5. Quality of Life in patients with nonalcoholic fatty liver disease: Structure and related factors focusing on illness uncertainty. Reviewed

    Naoki Ozawa, Kazuki Sato, Ayumi Sugimura, Shigeyoshi Maki, Taku Tanaka, Kenta Yamamoto, Takanori Ito, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Masatoshi Ishigami, Mitsuhiro Fujishiro, Tetsuya Ishikawa, Shoko Ando

    Japan journal of nursing science : JJNS   Vol. 18 ( 3 ) page: e12415   2021.3

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    AIM: Patients with nonalcoholic fatty liver disease (NAFLD) have a low quality of life (QOL) and illness uncertainty. This study examined the structure of QOL and associated factors, including illness uncertainty, among individuals with NAFLD. METHODS: A cross-sectional survey was conducted using a self-administered questionnaire for outpatients with NAFLD. QOL was measured using the Short Form-8. Dietary habits, physical activity level, illness uncertainty, health locus of control, and knowledge of NAFLD were assessed. Path analysis was used to study the associated factors of QOL and their structure, including uncertainty of disease. RESULTS: Path analysis of 168 NAFLD patients indicated that a high Physical Component Summary score on the Short Form-8-representing physical QOL-was predicted by a body mass index <25 kg/m2 and high educational level. A high Mental Component Summary score-representing mental QOL-was predicted by being male, good dietary habits, low illness uncertainty, and presence of consultants. The model showed satisfactory goodness-of-fit without being rejected by the chi-square test (goodness-of-fit index = .947, adjusted goodness-of-fit index = .917, comparative fit index = .967, root mean square error of approximation = 0.023). CONCLUSIONS: Nurses need to work closely with NAFLD patients as consultants, providing adequate information about the causes, treatments, and dietary habits, and focusing on the individual's perception of health. This could reduce illness uncertainty and contribute to the improvement of QOL.

    DOI: 10.1111/jjns.12415

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  6. Novel hepatitis B virus infection mouse model using herpes simplex virus type 1 thymidine kinase transgenic mice. Reviewed International journal

    Ayumu Kanbe, Tetsuya Ishikawa, Akira Hara, Hiroshi Suemizu, Eri Nanizawa, Yuki Tamaki, Hiroyasu Ito

    Journal of gastroenterology and hepatology   Vol. 36 ( 3 ) page: 782 - 789   2021.3

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    BACKGROUND AND AIM: The chronicity of hepatitis B virus (HBV) infection is the result of impaired HBV-specific immune responses that cannot eliminate or cure the infected hepatocytes efficiently. Previous studies have used immunodeficient mice such as herpes simplex virus type 1 thymidine kinase NOD/Scid/IL2Rrnull (HSV-TK-NOG) mice. However, it is difficult to analyze the immune response in the previous models. In the present study, we established a novel HBV infection model using herpes simplex virus type 1 thymidine kinase (HSV-TK) mice in which the host immune system was not impaired. METHODS: Herpes simplex virus type 1 thymidine kinase mice were injected intraperitoneally with ganciclovir (GCV). Seven days after GCV injection, GCV-treated mice were transplanted with 1 × 106 hepatocytes from HBV-transgenic (HBV-Tg) mice. RESULTS: Serum alanine aminotransferase levels in HSV-TK mice increased 1 and 2 weeks after GCV injection. The number and viability of hepatocytes from the whole liver of HBV-Tg mice significantly increased using digestion medium containing liberase. Hepatitis B surface antigen (HBsAg)-positive areas in the liver tissue were observed for at least 20 weeks after HBsAg-positive hepatocyte transplantation. In addition, we measured HBsAg in the serum after transplantation. HBsAg levels in HBV-Tg hepatocyte-replaced mice increased 4 weeks after transplantation. Furthermore, we examined the immune response in HSV-TK mice. The increase in hepatitis B surface antibody levels in replaced mice was maintained for 20 weeks. Also, interferon-γ-producing cells were increased in non-replaced mice. CONCLUSIONS: A novel HBV infection mouse model will help to understand the mechanisms of HBV tolerance similar to human chronic HBV-infected patients and can be used to develop a new strategy to treat chronic HBV infection.

    DOI: 10.1111/jgh.15142

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  7. 進行肝細胞癌に対するレンバチニブPD後のラムシルマブ治療の初期経験

    葛谷 貞二, 石上 雅敏, 杉山 由晃, 吉岡 直輝, 水野 和幸, 武藤 久哲, 横山 晋也, 田中 卓, 山本 健太, 伊藤 隆徳, 石津 洋二, 本多 隆, 石川 哲也, 藤城 光弘

    Pharma Medica   Vol. 39 ( 2 ) page: 72 - 73   2021.2

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  8. Free energy profile of permeation of Entecavir through Hepatitis B virus capsid studied by molecular dynamics calculation Invited Reviewed

    Fujimoto K., Fukai M., Urano R., Shinoda W., Ishikawa T., Omagari K., Tanaka Y., Nakagawa A., Okazaki S.

    Pure and Applied Chemistry   Vol. 92 ( 10 ) page: 1585 - 1594   2020.10

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    Entecavir, triphosphorylated in liver cells, is an antiviral reagent against Hepatitis B virus (HBV). The reagent inhibits reverse transcription of RNA inside the virus capsid. In the present study, free energy profile of an Entecavir triphosphate (ETVTP) molecule has been calculated when it passes through pores of the capsid along two- and three-fold rotational symmetry axes in order to investigate permeation pathway of the reagent to the inside of the capsid. The calculations have been done based on thermodynamic integration (TI) method combined with all-atomistic molecular dynamic (MD) calculations. A free energy minimum of -19 kJ/mol was found at the entrance of the pore from the outside along the three-fold symmetry axis. This stabilization is from the interaction of negatively charged ETVTP with positively charged capsid methionine residues. This excess free energy concentrates of the reagent at the entrance of the pore by a factor of about 2000. A free energy barrier of approximately 13 kJ/mol was also found near the exit of the pore to the inside of the capsid due to narrow space of the pore surrounded by hydrophobic wall made by proline residues and negatively charged wall by aspartic acid residues. There, ETVTP is partially dehydrated in order to pass through the narrow space, which causes the great free energy loss. Further, the negatively charged residues produce repulsive forces on the ETVTP molecule. In contrast, in the case of the pore along the two-fold symmetry axis, the calculated free energy profile showed shallower free energy minimum, -4 kJ/mol at the entrance in spite of the similarly high barrier, 7 kJ/mol, near the exit of the pore.

    DOI: 10.1515/pac-2020-0109

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  9. A prospective trial of vaccine to prevent hepatitis B virus reactivation after hematopoietic stem cell transplantation. Invited Reviewed International journal

    Koji Nishikawa, Kiminori Kimura, Yoshinobu Kanda, Masaya Sugiyama, Kazuhiko Kakihana, Noriko Doki, Kazuteru Ohashi, Sung Kwan Bae, Kazuhiro Takahashi, Yuko Ishihara, Ishikazu Mizuno, Yasushi Onishi, Masahiro Onozawa, Makoto Onizuka, Masahide Yamamoto, Tetsuya Ishikawa, Kazuaki Inoue, Shigeru Kusumoto, Satoshi Hashino, Hidetsugu Saito, Tatsuya Kanto, Hisashi Sakamaki, Masashi Mizokami

    Bone marrow transplantation   Vol. 55 ( 7 ) page: 1388 - 1398   2020.7

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    Hepatitis B virus (HBV) reactivation reportedly occurs frequently after hematopoietic stem cell transplantation (HSCT) in resolved HBV-infected patients. Here, 50 patients with resolved HBV infections and scheduled to undergo HSCT were enrolled; all subjects were vaccinated with three doses of hepatitis B vaccine 12 months after HSCT and the incidence of HBV reactivation was monitored. The patients' characteristics were: median age, 61 (34-72) years; male/female, 27/19; allogeneic/autologous, 40/6; bone marrow/peripheral blood stem cells/cord blood, 26/16/4. Of the 46 patients who underwent HSCT, 19 were excluded and did not make it to vaccination due to relapse of underlying disease, HBV reactivation within 12 months of HSCT, or transfer of patients. The remaining 27 were vaccinated 12 months after HSCT and monitored for 2 years. Six showed HBV reactivation, with a 2-year cumulative reactivation incidence of 22.2%; the same incidence was 27.3% only in allogeneic HSCT patients. Factors associated with HBV reactivation included the discontinuation of immunosuppressants (P = 0.0379) and baseline titers of antibody against hepatitis B surface antigen (P = 0.004). HBV reactivation with vaccination following HSCT could occur despite maintenance of serum anti-HBs at more than protective levels.

    DOI: 10.1038/s41409-020-0833-5

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  10. Short-term high-fat diet intake leads to exacerbation of concanavalin A-induced liver injury through the induction of procoagulation state. Reviewed International journal

    Eri Nanizawa, Yuki Tamaki, Reika Sono, Rintaro Miyashita, Yumi Hayashi, Ayumu Kanbe, Hiroyasu Ito, Tetsuya Ishikawa

    Biochemistry and biophysics reports   Vol. 22   page: 100736 - 100736   2020.7

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    Obesity and high-fat diet (HFD) are known to cause proinflammatory and procoagulation states and suggested to become a risk of developing thromboembolic diseases. Non-alcoholic fatty liver disease (NAFLD) is usually associated with obesity and HFD, and a part of NAFLD is known to progress to nonalcoholic steatohepatitis (NASH), the pathogenesis of which has not been fully elucidated. In the current study, we examined the influence of short-term HFD on hepatic expression of the molecules related to inflammation, coagulation, metabolism, and cellular stresses from the perspective that HFD itself can be a risk for the development to NASH. In the analysis in short-term (4 days to 14 days) HFD-fed mice, we found out that HFD increased hepatic expression of IFN-γ, TNF-α, IL-10, monocyte chemotactic protein-1 (MCP-1), tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1) mRNAs, and fibrin/fibrinogen deposition in the liver tissues. And it was suggested that metabolic alterations and endoplasmic reticulum (ER) stresses induced by the HFD intake were associated with this proinflammatory and procoagulation states. When we administered concanavalin A (Con A) to these HFD-fed mice, the extent of liver injury was dramatically exacerbated in HFD-fed mice. Heparin treatment to Con A-administered, HFD-fed mice (for 4 days) profoundly ameliorated the extent of liver injury. These suggest that even short-term of HFD intake induces proinflammatory and procoagulation states in the liver and thereby increases the susceptibility of the liver to circulating inflammatory stimuli. We think that it may explain a part of NASH pathogenesis.

    DOI: 10.1016/j.bbrep.2020.100736

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  11. Complete response of advanced hepatocellular carcinoma achieved by sorafenib dose re-escalation after failure of long-term low-dose-sorafenib treatment combined with transcatheter arterial chemoembolization: a case report. Reviewed

    Hisanori Muto, Teiji Kuzuya, Takanori Ito, Yoji Ishizu, Takashi Honda, Tetsuya Ishikawa, Masatoshi Ishigami, Mitsuhiro Fujishiro

    Clinical journal of gastroenterology   Vol. 13 ( 3 ) page: 397 - 402   2020.6

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    Few reports have described dose re-escalation after long-term low-dose sorafenib leading to good outcomes. Here, we report the case of an 80-year-old woman with advanced hepatocellular carcinoma who achieved complete response from sorafenib dose re-escalation after the failure of long-term low-dose sorafenib treatment combined with transcatheter arterial chemoembolization. Sorafenib therapy was initiated at 400 mg once daily due to old age and low platelet count. 5 months later, this dose was reduced to 200 mg once daily because of adverse events. Best radiological antitumor response by sorafenib treatment alone was judged as stable disease according to the modified Response Evaluation Criteria in Solid Tumors. 1 year later, she showed progressive disease owing to the progression of intrahepatic lesions. She received combination therapy with low-dose sorafenib (200 mg every other day) and transcatheter arterial chemoembolization, which proved relatively effective for three and a half years. Antitumor response by the fourth transcatheter arterial chemoembolization and subsequent low-dose sorafenib was clearly progressive disease. At that time, sorafenib-related adverse events were well-controlled. Sorafenib dose was re-escalated to 200 mg once daily. After this re-escalation, tumor markers declined rapidly, and adverse events remained tolerable. 4 months later, complete response was achieved.

    DOI: 10.1007/s12328-019-01066-7

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  12. Correlation of serum zinc levels with pathological and laboratory findings in patients with nonalcoholic fatty liver disease. Reviewed International journal

    Takanori Ito, Masatoshi Ishigami, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Tetsuya Ishikawa, Hidenori Toyoda, Takashi Kumada, Mitsuhiro Fujishiro

    European journal of gastroenterology & hepatology   Vol. 32 ( 6 ) page: 748 - 753   2020.6

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    OBJECTIVE: Chronic liver diseases are associated with zinc (Zn) deficiency. However, no previous studies have examined the relationship between serum Zn levels and hepatic pathological findings in patients with nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the serum Zn levels in NAFLD patients based on pathological/laboratory findings. METHODS: We evaluated a total of 191 NAFLD patients who underwent liver biopsy with the goal of identifying laboratory markers and pathological findings associated with serum Zn levels. RESULTS: Zn levels significantly decreased along with progression of hepatic fibrosis (P = 0.039), but there were no significant differences among inflammatory grades. Zn levels were most strongly correlated with albumin levels (r = 0.410, P < 0.001). In addition, Zn levels were significantly correlated with homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.284, P < 0.001), hyaluronic acid (r = -0.230, P < 0.001), branched chain amino acid/tyrosine molar ratio (BTR) (r = 0.278, P < 0.001), FIB-4 index (r = -0.238, P < 0.001), and NAFLD fibrosis score (NFS) (r = -0.261, P < 0.001). In multivariate analysis, albumin [odds ratio (OR), 9.244 (per 1 g/dL decrease) [95% confidence interval (CI), 2.261-32.744]; P < 0.001], BTR [OR, 1.545 (per 1 decrease) (95% CI, 1.115-2.140); P = 0.009], and HOMA-IR [OR, 1.048 (per 1 increase) (95% CI, 1.019-1.167); P = 0.028] were significantly associated with Zn deficiency. CONCLUSION: The progression of liver fibrosis, but not inflammation, is associated with lower serum Zn levels in biopsy-proven NAFLD patients. Serum Zn levels were correlated with nutrition markers and insulin resistance.

    DOI: 10.1097/MEG.0000000000001587

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  13. Sorafenib vs. Lenvatinib as First-line Therapy for Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis. Reviewed International journal

    Teiji Kuzuya, Masatoshi Ishigami, Takanori Ito, Yoji Ishizu, Takashi Honda, Tetsuya Ishikawa, Mitsuhiro Fujishiro

    Anticancer research   Vol. 40 ( 4 ) page: 2283 - 2290   2020.4

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    BACKGROUND/AIM: We aimed to compare the outcomes between sorafenib and lenvatinib as first-line therapy for advanced hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (Vp3/4). PATIENTS AND METHODS: This retrospective study enrolled 41 HCC patients with Vp3/4 and Child-Pugh A. RESULTS: The outcomes in the lenvatinib group (n=13) were significantly better than those in the sorafenib group (n=28) [best objective response rate according to the modified Response Evaluation Criteria in Solid Tumors: 53.8% vs. 14.3%; p=0.0193, best disease control rate: 92.3% vs. 35.7%; p=0.0008, median overall survival (OS): not reached vs. 187 days; p=0.0040, respectively]. Lenvatinib treatment was the only significant predictor of better OS and time to tumor progression. No patient needed to discontinue lenvatinib treatment due to drug-related adverse events. CONCLUSION: Compared with sorafenib, lenvatinib treatment for advanced HCC with Vp3/4 may lead to more favorable outcomes.

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  14. Initial Experience of Ramucirumab Treatment After Lenvatinib Failure for Patients With Advanced Hepatocellular Carcinoma. Reviewed International journal

    Teiji Kuzuya, Masatoshi Ishigami, Takanori Ito, Yoji Ishizu, Takashi Honda, Tetsuya Ishikawa, Mitsuhiro Fujishiro

    Anticancer research   Vol. 40 ( 4 ) page: 2089 - 2093   2020.4

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    BACKGROUND/AIM: The outcomes of ramucirumab after lenvatinib failure for hepatocellular carcinoma (HCC) patients with alpha fetoprotein (AFP) levels of ≥400 ng/ml are unknown. PATIENTS AND METHODS: Of 12 patients treated with ramucirumab after lenvatinib failure, 10 patients were enrolled in this retrospective study. RESULTS: The disease control rate of 80% at 6 weeks and the median time to progression of 3.1 months were the same by both the Response Evaluation Criteria in Solid Tumors (RECIST) and the modified RECIST. AFP reduction was seen in 5 patients at 2 weeks and in 3 patients at 6 weeks. The incidence of grade 3 adverse events was low at 10%. The albumin-bilirubin scores within 6 weeks did not worsen. CONCLUSION: Ramucirumab might have potential therapeutic efficacy and safety in advanced HCC patients after lenvatinib failure. Further studies are needed to confirm the outcomes of ramucirumab after lenvatinib failure.

    DOI: 10.21873/anticanres.14167

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  15. Favorable radiological antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma. Reviewed International journal

    Teiji Kuzuya, Masatoshi Ishigami, Takanori Ito, Yoji Ishizu, Takashi Honda, Tetsuya Ishikawa, Mitsuhiro Fujishiro

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 50 ( 3 ) page: 374 - 381   2020.3

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    AIM: We aimed to investigate the radiological antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma in real-world practice. METHODS: This retrospective study enrolled 40 patients who received lenvatinib. Radiological antitumor response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. RESULTS: The objective response rate at 2 weeks and best overall response on confirmation of complete response, partial response (PR), and stable disease required (confirmed response) were 57.5% and 32.5%, respectively. Based on confirmed response, the overall survival rate was significantly longer in patients with an objective response rate than in those with stable disease or progressive disease after 12 months (73.2% and 54.2%, P = 0.0358). All 13 patients with an objective response rate on confirmed response were evaluated as PR at 2 weeks. The alpha-fetoprotein ratio at 2 weeks was a significant factor associated with PR of response rate at 2 weeks. The median relative dose intensity from 2 to 6 weeks was significantly lower than that from 0 to 2 weeks (69.6% vs. 100%, P < 0.0001). Stratified by the antitumor response at 6 weeks considering the image evaluation at 2 weeks, the median relative dose intensity from 2 to 6 weeks was significantly lower in patients with progressive disease than in those with PR or stable disease (45.2% vs. 72.6%, P = 0.0482). CONCLUSIONS: The radiological antitumor response at 2 weeks was favorable. Information on a favorable visible therapeutic response very early after lenvatinib initiation can help patients maintain their motivation for treatment, and allow physicians to continue treatment effectively and safely.

    DOI: 10.1111/hepr.13452

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  16. Effect of weight change and lifestyle modifications on the development or remission of nonalcoholic fatty liver disease: sex-specific analysis. Reviewed International journal

    Naoki Yoshioka, Masatoshi Ishigami, Yasuko Watanabe, Hajime Sumi, Masao Doisaki, Takeo Yamaguchi, Takanori Ito, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Tetsuya Ishikawa, Jun-Ichi Haruta, Mitsuhiro Fujishiro

    Scientific reports   Vol. 10 ( 1 ) page: 481 - 481   2020.1

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    The effects of changes in various lifestyle habits on nonalcoholic fatty liver disease (NAFLD) have not been well elucidated. We aimed to clarify how weight change and lifestyle modifications were associated with the development or remission of NAFLD. In this longitudinal cohort study, we reviewed the periodic health checkup data of 1,421 subjects with no causes of liver disease besides NAFLD who had received at least two health checkups between 2009 and 2018. The prevalence of NAFLD at baseline was 34.1% (484/1,421). During follow-up period (4.6 ± 2.8 years), 104 subjects developed NAFLD and 127 subjects demonstrated NAFLD remission. The frequency of NAFLD development or that of NAFLD remission significantly increased as the larger weight gain or weight loss was, respectively (both, p < 0.001). Approximately 40% of the subjects who maintained ≥ 1%/year weight loss achieved NAFLD remission. By multivariate analysis, quitting smoking were independently associated with NAFLD development (adjusted odds ratio [AOR], 2.86; 95% CI, 1.24-6.62). Subjects who quit smoking demonstrated large weight gain (≥1%/year) significantly more frequently than the other subjects (p < 0.001). In sex-specific analysis, starting to exercise was independently associated with NAFLD remission in men (AOR, 2.38; 95% CI, 1.25-4.53).

    DOI: 10.1038/s41598-019-57369-9

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  17. Efficacy and Safety of Sorafenib in Unresectable Hepatocellular Carcinoma with Bile Duct Invasion. International journal

    Taku Tanaka, Teiji Kuzuya, Masatoshi Ishigami, Takanori Ito, Yoji Ishizu, Takashi Honda, Tetsuya Ishikawa, Mitsuhiro Fujishiro

    Oncology   Vol. 98 ( 9 ) page: 621 - 629   2020

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    INTRODUCTION: Because the frequency of bile duct invasion in hepatocellular carcinoma (HCC) patients is very rare, there is limited clinical evidence to demonstrate the outcomes of systemic therapy in HCC with bile duct invasion. OBJECTIVE: Our aim was to clarify the efficacy and safety of sorafenib treatment in patients with unresectable advanced HCC with bile duct invasion. METHODS: One hundred and seventy-five patients with advanced HCC were enrolled in this study. We retrospectively compared the outcomes of sorafenib between patients without bile duct invasion [B (-) group, n = 165] and those with bile duct invasion [B (+) group, n = 10]. RESULTS: There were no significant differences in the confirmed objective response rate (ORR) and the confirmed disease control (DC) rate between the B (-) and the B (+) groups (13.9 vs. 20.0%, p = 0.637 for ORR; 47.2 vs. 70.0%, p = 0.202 for DC rate, respectively). There were no significant differences in median overall survival (OS) and time to progression (TTP) between the B (-) group and the B (+) group (14.8 vs. 14.1 months, p = 0.780 for OS; 3.4 vs. 5.7 months, p = 0.277 for TTP, respectively). Post-treatment factors associated with good OS were changes in albumin-bilirubin score (0-6 weeks) of <0.25, and antitumor response at 6 weeks of DC. Though 5 of 10 patients (50%) in the B (+) group had bile duct complications, such as obstructive jaundice and biliary bleeding, these 5 patients were able to recover from biliary troubles by careful and vigorous management with biliary endoscopic intervention, and were able to continue sorafenib therapy safely. CONCLUSIONS: Our present results suggest that sorafenib might have potential therapeutic efficacy and safety in advanced HCC patients with bile duct invasion. In case of biliary tract troubles before and during sorafenib treatment, early biliary management may be important to continue sorafenib therapy safely. Further studies are needed to confirm the outcomes of sorafenib in advanced HCC patients with bile duct invasion.

    DOI: 10.1159/000507051

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  18. Sarcopenia impairs health-related quality of life in cirrhotic patients. Reviewed International journal

    Yusuke Ando, Masatoshi Ishigami, Takanori Ito, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Tetsuya Ishikawa, Mitsuhiro Fujishiro

    European journal of gastroenterology & hepatology   Vol. 31 ( 12 ) page: 1550 - 1556   2019.12

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    AIM: Sarcopenia is associated with poor health-related quality of life (HRQOL) in the general population. However, in cirrhotic patients, as the development of sarcopenia is closely related to declined liver function, which also impairs HRQOL, whether sarcopenia deteriorates HRQOL independently from declined liver function remains unclear. The aim of this study was to clarify the impact of sarcopenia on HRQOL impairment in cirrhotic patients. PATIENTS AND METHODS: A total of 88 cirrhotic patients [median age, 69 years; range: 31-79 years; 49 male (55.7%), 45 with hepatocellular carcinoma (51.1%)] were analyzed. We measured HRQOL using the 36-item Short-Form Health Survey version 2 questionnaire and identified factors contributing to scores lower than 50 in physical component summary (PCS), mental component summary, and role-social component summary (RCS) scores. RESULTS: Twenty-four (27.2%) patients had sarcopenia. PCS and RCS scores were significantly lower in patients with sarcopenia compared with those without sarcopenia. Patients with Child-Pugh (CP) classification B or C showed significantly lower scores in PCS and RCS than those with CP classification A. On multivariate analysis, the presence of sarcopenia was the only factor associated with low PCS scores [odds ratio (OR): 11.6; P = 0.031]. Female sex (OR: 3.34; P = 0.034), CP classification B or C (OR: 3.19; P = 0.037), and presence of sarcopenia (OR: 4.64; P = 0.016) were identified as independent factors for low RCS scores. CONCLUSION: Sarcopenia independently impairs physical and role-social HRQOL in cirrhotic patients.

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  19. Successful Treatment of Hepatocellular Carcinoma with Regorafenib after Sorafenib-induced Hypersensitivity. Reviewed

    Naoki Yoshioka, Teiji Kuzuya, Takanori Ito, Yoji Ishizu, Takashi Honda, Tetsuya Ishikawa, Masatoshi Ishigami, Mitsuhiro Fujishiro

    Internal medicine (Tokyo, Japan)   Vol. 58 ( 19 ) page: 2803 - 2808   2019.10

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    Sorafenib and regorafenib are tyrosine kinase inhibitors that are used in the treatment of hepatocellular carcinoma and which have similar chemical structures and toxicity profiles. We herein report a case in which regorafenib treatment could be continued for 10 months and stable disease could be maintained for a long period despite the discontinuation of sorafenib due to grade 4 liver injury and grade 3 fever. The severe adverse events could be attributed to drug hypersensitivity, since a drug-induced lymphocyte stimulation test (DLST) indicated sensitivity to sorafenib. A DLST for regorafenib was negative. This is the first report showing that regorafenib could be safely administered after the discontinuation of sorafenib due to hypersensitivity.

    DOI: 10.2169/internalmedicine.2812-19

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  20. Clinical characteristics and outcomes of candidates for second-line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment. Reviewed International journal

    Teiji Kuzuya, Masatoshi Ishigami, Takanori Ito, Yoji Ishizu, Takashi Honda, Tetsuya Ishikawa, Yoshiki Hirooka, Mitsuhiro Fujishiro

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 49 ( 9 ) page: 1054 - 1065   2019.9

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    AIM: This study aimed to investigate the clinical characteristics and outcomes of candidates for second-line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma (HCC) after sorafenib treatment. METHODS: Of 122 patients, 103 were radiologically confirmed as progressive disease (PD) (sorafenib-refractory group), and 19 discontinued sorafenib therapy due to adverse events prior to radiologic PD (sorafenib-intolerant group). Patients in the sorafenib-refractory group were divided into two subgroups each, according to their eligibility for second-line treatment (second-line-in and -out group), regorafenib (RESORCE-in and -out group), or ramucirumab (REACH-2-in and -out group). RESULTS: Patients included in the non-candidate group were those with α-fetoprotein level <400 ng/mL (n = 51, 49.5%), daily sorafenib dose <400 mg (n = 44, 42.7%), Child-Pugh B or C (n = 40, 38.8%), and Eastern Cooperative Oncology Group performance status score ≥2 (n = 24, 23.3%). The percentages of candidates were 57.3% for second-line, 35.0% for regorafenib, and 23.3% for ramucirumab. The median post-progression survival (PPS) was significantly longer for the second-line-in and the RESORCE-in groups than in the non-candidate groups (12.6 and 11.0 months vs. 3.0 and 6.1 months, respectively). The PPS was not significantly different between the REACH-2-in and -out groups. A significant predictor of candidates for second-line treatment at sorafenib initiation was a Child-Pugh score of 5 (A5). CONCLUSIONS: Not all patients refractory to sorafenib were candidates for second-line therapy. A Child-Pugh score of A5 at sorafenib initiation was an important and favorable factor related to eligibility for second-line therapy and good outcomes.

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  21. Induction of humoral and cellular immune response to HBV vaccine can be up-regulated by STING ligand. Reviewed International journal

    Hiroyasu Ito, Ayumu Kanbe, Akira Hara, Tetsuya Ishikawa

    Virology   Vol. 531   page: 233 - 239   2019.5

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    A persistent hepatitis B virus (HBV) infection is characterized by a lack of or a weak immune response to HBV. Efficient induction of the HBV-specific immune response leads to the clearance of HBV. Stimulator of interferon (IFN) genes (STING) is a cytoplasmic sensor of intracellular DNA from microbes and host cells. In the present study, we examined the efficacy of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) that is a ligand of the STING pathway as an HBV vaccine adjuvant. Wild-type (WT) mice and HBV-transgenic (HBV-Tg) mice were immunized with hepatitis B surface antigen (HBsAg) and cGAMP. The vaccination with HBsAg and cGAMP significantly enhanced the humoral and cellular immune response to HBsAg in WT and HBV-Tg mice. Cytokine production related to Th1 and Th2 responses and the activation of antigen-presenting cells in lymphoid tissues were induced by cGAMP. Vaccination using cGAMP may overcome tolerance in patients with chronic HBV infection.

    DOI: 10.1016/j.virol.2019.03.013

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  22. In utero exposure to di(2-ethylhexyl)phthalate suppresses blood glucose and leptin levels in the offspring of wild-type mice. Reviewed International journal

    Yumi Hayashi, Yuki Ito, Hisao Naito, Hazuki Tamada, Nozomi Yamagishi, Takaaki Kondo, Tetsuya Ishikawa, Frank J Gonzalez, Tamie Nakajima

    Toxicology   Vol. 415   page: 49 - 55   2019.3

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    Exposure of pregnant mice to di(2-ethylhexyl)phthalate (DEHP) induces maternal lipid malnutrition and decreases the number of live fetuses/pups. In this study, we aimed to clarify the relationship between maternal lipid malnutrition and the nutritional status of the neonatal, lactational, and adult offspring, as well as the role of peroxisome proliferator-activated receptor α (PPARα) in these relationships. Sv/129 wild-type (mPPARA), Ppara-null, and PPARα-humanized (hPPARA) mice were fed diets containing 0, 0.01, 0.05, or 0.1% DEHP in utero and/or during the lactational stage. The male offspring were killed on postnatal day 2 or 21, or after 11 weeks. Exposure to either 0.05% or 0.1% DEHP during both the in utero and lactational periods decreased serum glucose concentrations in 2-day-old mPPARA offspring. These dosages also decreased both serum and plasma leptin levels in both 2- and 21-day-old mPPARA offspring. In contrast, exposure to DEHP only during the lactational period did not decrease leptin levels, suggesting the importance of in utero exposure to DEHP. Exposure to 0.05% DEHP during the in utero and lactational periods also increased food consumption after weaning in both mPPARA and hPPARA mice; this was not observed in Ppara-null offspring. In conclusion, in utero exposure to DEHP induces neonatal serum glucose malnutrition via PPARα. DEHP also decreases serum and plasma leptin concentrations in offspring during the neonatal and weaning periods, in association with PPARα, which presumably results in increased of food consumption after weaning.

    DOI: 10.1016/j.tox.2019.01.008

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  23. Corrigendum to "Intact metabolite profiling of mouse brain by probe electrospray ionization/triple quadrupole tandem mass spectrometry (PESI/MS/MS) and its potential use for local distribution analysis of the brain" [ACA 983 (2017) 160-165]. International journal

    Yumi Hayashi, Kei Zaitsu, Tasuku Murata, Tomomi Ohara, Stéphane Moreau, Maiko Kusano, Hiroshi Tanihata, Hitoshi Tsuchihashi, Akira Ishii, Tetsuya Ishikawa

    Analytica chimica acta   Vol. 1031   page: 196 - 196   2018.11

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    DOI: 10.1016/j.aca.2018.08.001

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  24. Effective Transplantation of 2D and 3D Cultured Hepatocyte Spheroids Confirmed by Quantum Dot Imaging Reviewed

    Hiroki Okumura, Eri Nanizawa, Anna Nakanishi, Hiroshi Yukawa, Tadahiro Hashita, Takahiro Iwao, Yoshinobu Baba, Tetsuya Ishikawa, Tamihide Matsunaga

    Advanced Biosystems   Vol. 2 ( 8 )   2018.8

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    © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Liver transplantation is the most effective treatment for patients with end-stage liver diseases, but hepatocyte transplantation using spheroids is expected to become an alternative strategy owing to the limited number of liver donors. However, the effects of the transplantation route and spheroid size on cell dynamics and the organ-specific accumulation of hepatocytes are not well characterized. In this study, the influence of three delivery routes (tail vein, portal vein, and spleen) and three spheroid sizes (50, 100, and 150 µm in diameter) on the accumulation of human fetal hepatocytes labeled with quantum dots in the liver and other organs (heart, lung, kidney, and spleen) of recipient mice is investigated. Ex vivo fluorescence imaging reveals that the accumulation of transplanted cells in the liver is highest for transplantation via the portal vein compared with other routes. The accumulation efficiency depends on spheroid size, and spheroids with a diameter of 50 µm display greater accumulation than that of spheroids of other sizes. It is concluded that hepatocyte transplantation via the portal vein using small spheroids of 50 µm in diameter may be effective for clinical applications.

    DOI: 10.1002/adbi.201800137

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  25. (-)-Epigallocatechin-3-gallate Down-regulates Doxorubicin-induced Overexpression of P-glycoprotein Through the Coordinate Inhibition of PI3K/Akt and MEK/ERK Signaling Pathways

    Satonaka Hana, Ishida Kumiki, Takai Miho, Koide Ryoji, Shigemasa Ryota, Ueyama Jun, Ishikawa Tetsuya, Hayashi Kazuhiko, Goto Hidemi, Wakusawa Shinya

    ANTICANCER RESEARCH   Vol. 37 ( 11 ) page: 6071-6077   2017.11

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    DOI: 10.21873/anticanres.12055

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  26. Effects of Ursodeoxycholic Acid and Insulin on Palmitate-Induced ROS Production and Down-Regulation of PI3K/Akt Signaling Activity

    Yokoyama Kunihiro, Tatsumi Yasuaki, Hayashi Kazuhiko, Goto Hidemi, Ishikawa Tetsuya, Wakusawa Shinya

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   Vol. 40 ( 11 ) page: 2001-2004   2017.11

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  27. Utility of Doppler ultrasonography for diagnosing and assessing treatment effects in liver compartment syndrome. Reviewed

    Yusuke Ando, Masatoshi Ishigami, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Kazuhiko Hayashi, Tetsuya Ishikawa, Hidemi Goto, Yoshiki Hirooka

    Clinical journal of gastroenterology   Vol. 10 ( 3 ) page: 265 - 269   2017.6

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    Liver compartment syndrome is a life-threatening complication of hepatic subcapsular hematoma; diagnosis and assessment of treatment effects are therefore important. We report a rare case of liver compartment syndrome due to spontaneous hepatic subcapsular hematoma without any underlying conditions, in which Doppler ultrasonography (US) proved useful in both diagnosis and assessment of treatment effects. A 32-year-old woman experienced sudden epigastralgia and was diagnosed with hepatic subcapsular hematoma in the right lobe, based on contrast-enhanced computed tomography. Hepatic arteriography showed active hemorrhage and Doppler US showed retrograde flow in the right portal vein. From these findings, we diagnosed hepatic subcapsular hematoma complicated with liver compartment syndrome, and performed embolization of the bleeding point and percutaneous hematoma drainage. After these medical procedures, normalized antegrade flow in the right portal vein was observed on Doppler US. No underlying conditions contributing to hematoma were identified. In this case, Doppler US was useful for both diagnosis and assessment of treatment effects in liver compartment syndrome. When we examine patients with hepatic subcapsular hematoma, Doppler US should be used to diagnose the presence of liver compartment syndrome and assess treatment effects.

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  28. Coexistence of Copper in the Iron-Rich Particles of Aceruloplasminemia Brain. Reviewed International journal

    Kunihiro Yoshida, Hisao Hayashi, Shinya Wakusawa, Ryota Shigemasa, Ryoji Koide, Tetsuya Ishikawa, Yasuaki Tatsumi, Koichi Kato, Shinji Ohara, Shu-Ichi Ikeda

    Biological trace element research   Vol. 175 ( 1 ) page: 79 - 86   2017.1

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    The interaction between iron and copper has been discussed in association with human health and diseases for many years. Ceruloplasmin, a multi-copper oxidase, is mainly involved in iron metabolism and its genetic defect, aceruloplasminemia (ACP), shows neurological disorders and diabetes associated with excessive iron accumulation, but little is known about the state of copper in the brain. Here, we investigated localization of these metals in the brains of three patients with ACP using electron microscopes equipped with an energy-dispersive x-ray analyzer. Histochemically, iron deposition was observed mainly in the basal ganglia and dentate nucleus, and to lesser degree in the cerebral cortex of the patients, whereas copper grains were not detected. X-ray microanalysis identified two types of iron-rich particles in their brains: dense bodies, namely hemosiderins, and their aggregated inclusions. A small number of hemosiderins and most inclusions contained a significant amount of copper which was enough for distinct Cu x-ray images. These copper-containing particles were observed more frequently in the putamen and dentate nucleus than the cerebral cortex. Coexistence of iron and copper was supported by good correlations in the molecular ratios between these two metals in iron-rich particles with Cu x-ray image. Iron-dependent copper accumulation in iron-rich particles may suggest that copper recycling is enhanced to meet the increased requirement of cuproproteins in iron overload brain. In conclusion, the iron-rich particles with Cu x-ray image were found in the ACP brain.

    DOI: 10.1007/s12011-016-0744-x

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  29. 近赤外バイオイメージング-NIR-II:第2の生体の窓 NIR-II近赤外領域における移植幹細胞in vivo蛍光イメージング

    湯川博, 小林香央里, 湯川博, 小林香央里, 新岡宏彦, 亀山達矢, 佐藤和秀, 鳥本司, 石川哲也, 馬場嘉信, 馬場嘉信

    Bio Industry   Vol. 34 ( 1 ) page: 113 - 113   2017

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  30. Metabolome analysis revealed that abnormal muscular contraction is related to both metabolic alterations and hyper-thermogenesis in the serotonin syndrome

    ZAITSU Kei, NODA Saki, HAYASHI Yumi, OHARA Tomomi, IGUCHI Akira, KUSANO Maiko, SATO Takako, TSUCHIHASHI Hitoshi, ISHIKAWA Tetsuya, SUZUKI Koichi, ISHII Akira

    Annual Meeting of the Japanese Society of Toxicology   Vol. 44.1 ( 0 ) page: O-38   2017

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    DOI: 10.14869/toxpt.44.1.0_o-38

    CiNii Research

  31. Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 identified from Dental Pulp Stem Cells Synergistically Resolve Acute Liver Failure in Rats by Altering Macrophage Polarity Reviewed

    Takanori Ito, Akihito Yamamoto, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Tetsuya Ishikawa, Masatoshi Ishigami, Yoshiki Hirooka, Hidemi Goto

    HEPATOLOGY   Vol. 64   page: 515A - 515A   2016.10

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  32. Investigation of cocaine-induced hepatic injury in PPARα-null mice on the basis of lipid mediators and metabolome analyses

    SHINODA Satoshi, HAYASHI Yumi, ZAITSU Kei, SAKAI Yuichiro, YAMANAKA Mayumi, NASU Tamie, ISHIKAWA Tetsuya, YOSHIMOTO Takashi, KUSANO Maiko, TSUCHIHASHI Hitoshi, ISHII Akira

    Annual Meeting of the Japanese Society of Toxicology   Vol. 43.1 ( 0 ) page: P-90   2016

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    DOI: 10.14869/toxpt.43.1.0_p-90

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  33. [Pathogenesis and disease state in hepatitis B virus infection].

    Ishikawa T

    Nihon rinsho. Japanese journal of clinical medicine   Vol. 73 Suppl 9   page: 429 - 33   2015.12

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  34. C型肝炎治療の現状 Invited

    石川哲也

    明日の臨床   Vol. 27 ( 1 ) page: 29-34   2015.6

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  35. Kynurenine production mediated by indoleamine 2,3-dioxygenase aggravates liver injury in HBV-specific CTL-induced fulminant hepatitis. Reviewed

    OHTAKI Hirofumi, ITO Hiroyasu, ANDO Kazuki, ISHIKAWA Tetsuya, HOSHI Masato, ANDO Tatsuya, TAKAMATSU Manabu, HARA Akira, MORIWAKI Hisataka, SAITO Kuniaki, SEISHIMA Mitsuru

    Biochim Biophys Acta   Vol. 1842 ( 9 ) page: 1464–1471   2014.9

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    Indoleamine 2,3-dioxygenase (IDO), an enzyme that is ubiquitously distributed in mammalian tissues and cells, converts tryptophan to kynurenine, and is also known as a key molecule that promotes apoptosis in lymphocytes and neurons. In this study, we established hepatitis B virus (HBV)-transgenic (Tg)/IDO-knockout (KO) mice and examined the influence of IDO in a murine fulminant hepatitis model induced by HBV-specific cytotoxic T lymphocytes (CTL). An increase of IDO expression in the livers of HBV-Tg/IDO-wild-type (WT) mice administered HBV-specific CTL was confirmed by real-time polymerase chain reaction, western blotting, and evaluating IDO activity. Plasma alanine aminotransferase (ALT) levels in HBV-Tg/IDO-KO mice after HBV-specific CTL injection significantly decreased compared with those in HBV-Tg/IDO-WT mice. An inhibitor of IDO, 1-methyl-D-tryptophan (1-MT), could also attenuated the observed liver injury induced by this HBV-specific CTL. The expression levels of cytokine and chemokine mRNAs in the livers of HBV-Tg/IDO-WT mice were higher than those in the livers of HBV-Tg/IDO-KO mice. The administration of kynurenine aggravated the liver injury in HBV-Tg/IDO-KO mice injected with HBV-specific CTL. Simultaneous injection of recombinant murine interferon (IFN-γ) and kynurenine also increased the ALT levels in HBV-Tg/IDO-KO mice. The liver injury
    induced by IFN-γ and kynurenine was improved in HBV-Tg/tumor necrosis factor-α-KO mice. Conclusion:
    Kynurenine and IFN-γ induced by the administration with HBV-specific CTL are cooperatively involved in the
    progression of liver injury in acute hepatitis model. Our results may lead to a new therapy for the acute liver injury caused by HBV infection.

  36. Induction of hepatitis B virus surface antigen-specific cytotoxic T lymphocytes can be up-regulated by the inhibition of indoleamine 2, 3-dioxygenase activity. Reviewed

    ITO Hiroyasu, ANDO Tatsuya, ANDO Kazuki, ISHIKAWA Tetsuya, SAITO Kuniaki, MORIWAKI Hisataka, SEISHIMA Mitsuru

    Immunology   Vol. 142 ( 4 ) page: 614–623   2014.8

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    Cytotoxic T lymphocytes (CTLs) are thought to be major effectors involved in viral clearance during acute infections, including hepatitis B virus (HBV) infection. A persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which may be reflective of tolerance to HBV. Efficient induction of HBV-specific CTLs leads to the clearance of HBV in patients with a chronic HBV infection. Previously, we
    reported that a-galactosylceramide (a-GalCer), a specific natural killer T (NKT) cell agonist, enhanced the induction of HBV surface antigen (HBsAg)-specific CTLs. In the present study, we found that inhibition of
    indoleamine 2,3-dioxygenase (IDO) activity enhanced the induction of HBsAg-specific CTLs after immunization with HBsAg and a-GalCer. The administration of HBsAg and a-GalCer increased the production of interleukin-2 and interleukin-12b, which are crucial for the induction of HBsAg-specific CTLs. The production of these cytokines was more strongly enhanced in IDO knockout mice compared with wild-type mice. In addition, a-GalCer induced the production of IDO in CD11b+ cells, and these cells inhibited proliferation of HBsAg-specific CTLs. Our results lead to strategies for improving the induction of HBsAg-specific CTLs.

  37. Ursodeoxycholic acid inhibits overexpression of P-glycoprotein induced bydoxorubicin in HepG2 cells. Reviewed

    KOMORI Yuki, ARISAWA Sakiko, TAKAI Miho, YOKOYAMA Kunihiro, HONDA Minako, HAYASHI Kazuhiko, ISHIGAMI Masatoshi, KATANO Yoshiaki, GOTO Hidemi, UEYAMA Jun, ISHIKAWA Tetsuya, WAKUSAWA Shinya.

    European JournalofPharmacology   Vol. 724   page: 161-167   2014.2

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  38. 進行肝細胞癌に対するソラフェニブ投与後2週間以内の発熱と造影CT上の阻血性変化との関係 Reviewed

    葛谷貞二、石上雅敏、新家卓郎、今井則博、阿知波宏一、荒川恭宏、山田恵一、中野聡、石津洋二、本多隆、林和彦、石川哲也、中野功、片野義明、伊藤彰浩、廣岡芳樹、後藤秀実.

    肝臓   Vol. 54 ( 7 ) page: 505-506   2013.7

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  39. 満腹感を伴う便秘症状の原因にvildagliptinの関与が示唆された糖尿病合併末期腎不全の1例 Reviewed

    綾田穣、森弘卓延、加藤ふみ、堀田直樹、黒川剛、中野達徳、石川哲也

    腎と透析   Vol. 74 ( 3 ) page: 470-474   2013.3

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  40. Clinical trial of percutaneous radio frequency ablation therapy by two-step insertion method using VirtuTRAX<sup>TM</sup> instrument navigator Reviewed

    Kuzuya Teiji, Hayashi Kazuhiko, Ishigami Masatoshi, Ishikawa Tetsuya, Nakano Isao, Katano Yoshiaki, Itoh Akihiro, Hirooka Yoshiki, Izumi Namiki, Goto Hidemi, Ishizu Yoji, Niinomi Takurou, Imai Norihiro, Achiwa Kouichi, Arakawa Takahiro, Yamada Keiichi, Nakano Satoshi, Honda Takashi

    Kanzo   Vol. 54 ( 12 ) page: 850 - 853   2013

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    We performed percutaneous radio frequency ablation (RFA) therapy by two-step insertion method using VirtuTRAX<sup>TM</sup> (GE Healthcare, USA) instrument navigator. Subjects were 16 patients (23 nodules) with hepatocellular carcinoma. VirtuTRAX<sup>TM</sup> position sensor was attached to the hilt of 14-gauge outer needle. In all cases, we could perform 17- gauge Cool-tip RFA without the positional gap between the virtual tract and the actual needle which was caused by the deflection of the needle. The reasons without causing the positional gap were that the outer needle was more rigid than Cool-tip needle, and that it was inserted using initial insertion of a 21-gauge guided needle. RFA by two-step insertion method using VirtuTRAX<sup>TM</sup> is suggested to be more safe and effective than conventional RFA.

    DOI: 10.2957/kanzo.54.850

    Scopus

    CiNii Books

    J-GLOBAL

    Other Link: http://search.jamas.or.jp/link/ui/2014089120

  41. Quantum dots conjugated with transferrin for brain tumor cell imaging.

    Yukawa H, Tsukamoto R, Kano A, Okamoto Y, Tokeshi M, Ishikawa T, Mizuno M, Baba Y

    Journal of Cell Science and Therapy   Vol. 4 ( 3 ) page: 1   2013

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  42. Immunoregulation of hepatitis B virus infection -rationale and clinical application- Invited

    ISHIKAWA Tetsuya

    Nagoya J Med Sci   Vol. 74   page: 217-232   2012.8

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    Hepatitis B virus (HBV) is susceptible to the cellular immune responses, especially to the signal of interferon (IFN)-g. The action of IFN-g is pleiotropic, and causes downregulation of HBV in protein, RNA, and possibly DNA levels. Therefore, therapeutic vaccination to induce cellular immune responses to HBV is a promising approach for controlling chronic HBV infection. A number of clinical trials with this approach have been conducted to date, however, they have not been as successful as initially expected. T-cell exhaustion induced by the excessive HBV antigens caused by persistent infection is thought to be one of the main causes of poor responses to therapeutic vaccination. In this review, the mechanisms behind immunoregulation of HBV replication and immunodysfunction during chronic HBV infection are summarized, and novel approaches to improve the efficacy of therapeutic vaccination, from basic research to clinical trials, are introduced.

  43. 機能性胃疾患診療における不安抑うつスコアの有用性と機能性胃疾患の発症および増悪因子としての心配性の関与について

    洪繁、松浦俊博、木村宏之、石川哲也、京兼和宏、山田理

    消化器内科   Vol. 55 ( 1 ) page: 42-49   2012.7

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    HADS(Hospital Anxiety Depression Scale)スコアに本人の主観的性格分類(楽天的か心配性か)を組み合わせて解析することで、機能性胃腸症発症、増悪と心配性の性格の関わりについて解析した。職域検診を受診した健常者の解析からは、心配性の性格とHADSスコアが正に相関していた。更に、機能性胃腸症患者では、うつ病で治療中の患者と同様に心配性の患者の割合が非常に高く、患者の心配性の性格が機能性胃腸症発症及び増悪因子であることが疑われた。機能性胃腸症の診療においては、多くの患者が過度に心配性であり、胃腸症状の出現により更に心配性の度合いが高じていることを考慮し、患者の不安を取り除く診療を行うことが、患者の愁訴を減少させ、治療満足度を向上させる方法であると考えられる。

  44. 瀉血による慢性肝炎の進展予防

    伊東和樹, 石川哲也

    medicina   Vol. 48 ( 7 ) page: 1176-1178   2011.7

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    1-110//2-0//3-石川哲也

  45. 今月の主題 内科疾患の予防戦略 消化器疾患の予防戦略 瀉血による慢性肝炎の進展予防

    伊東 和樹, 石川 哲也

    medicina   Vol. 48 ( 7 ) page: 1176 - 1178   2011.7

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    DOI: 10.11477/mf.1402105262

    CiNii Research

  46. Association of interleukin 28B and mutations in the core and NS5A region of hepatitis C virus with response to peg-interferon and ribavirin therapy. Reviewed

    HAYASHI Kazuhiko, KATANO Yoshiaki, HONDA Takashi, ISHIGAMI Masatoshi, ITOH Akihiro, HIROOKA Yoshiki, ISHIKAWA Tetsuya, NAKANO Isao, YOSHIOKA Kentaro, TOYODA Hidenori, KUMADA Takashi, GOTO Hidemi

    Liver Int     page: 1359-1365   2011.6

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    Background and aims: Mutations in the core and NS5A region of hepatitis C virus (HCV) genotype 1b have been associated with response to interferon (IFN) therapy. Genome-wide association studies have revealed that the singlenucleotide polymorphism (SNP) of interleukin 28B (IL28B) contributes to IFN response. The aim of this study was to investigate whether the SNP of IL28B (rs8099917) and amino acid substitutions in the core and NS5A region affect the response to IFN therapy. Methods: A total of 299 patients (157 men, 142 women; mean age, 55.910.3 years) infected with HCV genotype 1b were studied. The fibrosis stage was diagnosed as F0 (n = 23), F1 (n = 121), F2 (n = 62), F3 (n = 32) and F4 (n = 7) by liver biopsy. Results: Of the 299 patients, 138 achieved sustained virological response (SVR). On univariate analysis, predictors of SVR were age o60 years, male gender, higher platelet count, lack of fibrosis, non-Q at core 70, mutant-type interferon sensitivitydetermining region (ISDR) and IL28B genotype TT. The factors related to SVR on multivariate analysis were IL28B (P = 0.0001), fibrosis (P = 0.0111) and mutations in the core region70 (P = 0.0267) and ISDR (P = 0.0408). The best SVR was achieved in patients with non-Q70, mutant-type ISDR and T allele (74.5%), and the worst was achieved in patients with Q70, wild-type
    ISDR and G allele (8.1%). Conclusions: The SNP of IL28B and mutations in the core region and NS5A are associated with IFN responsiveness. Both host and viral factors might be useful for predicting IFN response.

    DOI: 10.1111/j.1478-3231.2011.02571.x.

  47. バンコマイシン投与によって難治性肝性脳症が改善し肝細胞癌に対する肝動脈化学塞栓療法が可能となった1例

    葛谷 貞二, 竹田 欽一, 宇都宮 節夫, 多賀 雅浩, 川田 登, 池田 誉, 今井 則博, 水谷 佳貴, 広瀬 健, 石川 哲也

    癌と化学療法   Vol. 38 ( 6 ) page: 995 - 1001   2011.6

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    症例は80歳、男性。C型肝硬変、肝細胞癌で通院していた。2007年秋ごろから肝性脳症を繰り返すようになり、頻回の外来通院と入院加療を必要とした。肝予備能の低下により、肝細胞癌に対する治療は不可能となった。肝性脳症に対して緩下剤、ラクツロース、カナマイシン内服などの投与を行ったが、脳症のコントロールは困難であった。血中アンモニア値は130μg/dL前後で、時に200μg/dL以上となった。12月よりバンコマイシン内服(0.5g/回、3日に1回投与)を追加したところ、アンモニア値は速やかに50μg/dL低下となり、意識レベルの正常化、ADL、QOLの改善など著明な効果が得られた。バンコマイシン内服開始3ヵ月後には、Child C(10点)からChild B(7点)と肝予備能も改善、肝細胞癌に対し肝動脈化学塞栓療法が可能となった。(著者抄録)

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J00296&link_issn=&doc_id=20110629470023&doc_link_id=%2Fab8gtkrc%2F2011%2F003806%2F025%2F0995-0997%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2011%2F003806%2F025%2F0995-0997%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  48. Liver stiffness in extrahepatic cholestasis correlates positively with bilirubin and negatively with alanime aminotransferase

    HARATA Masao, HASHIMOTO Senju, KAWABE Naoto, NITTA Yoshifumi, MURAO Michihito, NAKANO Takuji, ARIMA Yuko, SHIMAZAKI Hiroaki, ISHIKAWA Tetsuya, OKUMURA Akihiko, ICHINO Naohiro, OSAKABE Keisuke, NISHIKAWA Toru, YOSHIOKA Kentaro

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 41 ( 5 ) page: 423 - 429   2011.5

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  49. 沈降型B型肝炎ワクチン Invited

    石川哲也

    肝胆膵   Vol. 61 ( 6 ) page: 1088-1094   2010.12

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  50. Hypofractionated stereotactic body radiotherapy for primary and metastatic liver tumors using the novalis image-guided system: preliminary results regarding efficacy and toxicity. Reviewed International journal

    Hiromitsu Iwata, Yuta Shibamoto, Chisa Hashizume, Yoshimasa Mori, Tatsuya Kobayashi, Naoki Hayashi, Katsura Kosaki, Tetsuya Ishikawa, Teiji Kuzuya, Setsuo Utsunomiya

    Technology in cancer research & treatment   Vol. 9 ( 6 ) page: 619 - 27   2010.12

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    www.tcrt.org The purpose of this study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for primary and metastatic liver tumors using the Novalis image-guided radiotherapy system. After preliminarily treating liver tumors using the Novalis system from July 2006, we started a protocol-based study in February 2008. Eighteen patients (6 with primary hepatocellular carcinoma and 12 with metastatic liver tumor) were treated with 55 or 50 Gy, depending upon their planned dose distribution and liver function, delivered in 10 fractions over 2 weeks. Four non-coplanar and three coplanar static beams were used. Patient age ranged from 54 to 84 years (median: 72 years). The Child-Pugh classification was Grade A in 17 patients and Grade B in 1. Tumor diameter ranged from 12 to 35 mm (median: 23 mm). Toxicities were evaluated according to the Common Terminology Criteria of Adverse Events version 4.0, and radiation-induced liver disease (RILD) was defined by Lawrence's criterion. The median follow-up period was 14.5 months. For all patients, the 1-year overall survival and local control rates were 94% and 86%, respectively. A Grade 1 liver enzyme change was observed in 5 patients, but no RILD or chronic liver dysfunction was observed. SBRT using the Novalis image-guided system is safe and effective for treating primary and metastatic liver tumors. Further investigation of SBRT for liver tumors is warranted. In view of the acceptable toxicity observed with this protocol, we have moved to a new protocol to shorten the overall treatment time and escalate the dose.

    PubMed

  51. Ability of IDO to attenuate liver injury in α-galactosylceramide- induced hepatitis model Reviewed

    Hiroyasu Ito, Masato Hoshi, Hirofumi Ohtaki, Ayako Taguchi, Kazuki Ando, Tetsuya Ishikawa, Yosuke Osawa, Akira Hara, Hisataka Moriwaki, Kuniaki Saito, Mitsuru Seishima

    Journal of Immunology   Vol. 185 ( 8 ) page: 4554 - 4560   2010.10

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    IDO converts tryptophan to L-kynurenine, and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, we examined the effect of IDO in α-galactosylceramide (α-GalCer)-induced hepatitis. The increase in IDO expression in the liver of wild-type (WT) mice administered α-GalCer was confirmed by real-time PCR, Western blotting, and IDO immunohistochemical analysis. The serum alanine aminotransferase levels in IDO-knockout (KO) mice after α-GalCer injection significantly increased compared with those in WT mice. 1-Methyl-D-tryptophan also exacerbated liver injury in this murine hepatitis model. In α-GalCer-induced hepatitis models, TNF-α is critical in the development of liver injury. The mRNA expression and protein level of TNF-α in the liver from IDO-KO mice were more enhanced compared with those in WT mice. The phenotypes of intrahepatic lymphocytes from WT mice and IDO-KO mice treated with α-GalCer were analyzed by flow cytometry, and the numbers of CD49b+ and CD11b+ cells were found to have increased in IDO-KO mice. Moreover, as a result of the increase in the number of NK cells and macrophages in the liver of IDO-KO mice injected with α-GalCer, TNF-α secretion in these mice was greater than that in WT mice. Deficiency of IDO exacerbated liver injury in α-GalCer-induced hepatitis. IDO induced by proinflammatory cytokines may decrease the number of TNF-α-producing immune cells in the liver. Thus, IDO may suppress overactive immune response in the α-GalCer-induced hepatitis model. Copyright © 2010 by The American Association of Immunologists, Inc.

    DOI: 10.4049/jimmunol.0904173

    Web of Science

    Scopus

    PubMed

  52. Role of tumor necrosis factor-α in acute hepatitis B virus infection

    Ito Hiroyasu, Ando Kazuki, Ishikawa Tetsuya, SEISHIMA Mitsuru

    炎症・再生 : 日本炎症・再生医学会雑誌 = Inflammation and regeneration   Vol. 30 ( 5 ) page: 445 - 450   2010.9

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  53. PEG後栄養管理中の義歯誤嚥に対しネット鉗子とオーバーチューブを用い安全に異物除去が可能であった1例 Reviewed

    綾田穣, 堀田直樹, 中野達徳, 内村正史, 花井恵美, 伊藤陽子, 徳永有姫, 吉田篤生, 石川哲也, 増子和郎

    在宅医療と内視鏡治療   Vol. 14 ( 1 ) page: 46-51   2010.9

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  54. A case of erythropoietic protoporphyria with severe liver damage Reviewed

    SHIMAZAKI Hiroaki, ARIMA Yuko, NAKANO Takuji, MURAO Michihito, NITTA Yoshifumi, HARATA Masao, KAWABE Naoto, HASHIMOTO Senju, NAGANO Kenichi, ISHIKAWA Tetsuya, OKUMURA Akihiko, HAYASHI Kazuhiko, KATANO Yoshiaki, KURODA Makoto, YOSHIOKA Kentaro

    Kanzo   Vol. 51 ( 4 ) page: 175 - 182   2010.4

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    Case is a 29-yr-old man, whose complaint was abdominal pain. He had photosensitivity since childhood. The paternal grandfather and the younger brother have photosensitivity. In November 2001, he admitted in the other hospital with liver dysfunction and was diagnosed as erythropoietic protoporphyria (EPP). In August 2005, he admitted with abdominal pain and jaundice and recovered with antibiotics. In January 2006, he was referred to our hospital with mild elevation of ALT. In November 2006 and in May 2007, he admitted in our hospital with abdominal pain and jaundice, and recovered with antibiotics. In August 2008, he admitted with the same symptoms. Erythrocyte protoporphyrin and total bilirubin continually elevated. He died from liver failure in November 2008. A small portion of EPP patients suffer from liver failure. The only effective treatment for liver failure of EPP is liver transplantation, which should be considered at appropriate timing of the disease course.<br>

    DOI: 10.2957/kanzo.51.175

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    CiNii Books

    Other Link: http://search.jamas.or.jp/link/ui/2010194025

  55. A case of metastatic pancreatic cancer with a remarkable response to to combination therapy of gemcitabine and adoptive immune cell therapy. Reviewed

      Vol. 37 ( 3 ) page: 527-529   2010.3

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  56. B型肝炎に対する免疫療法 Invited

    石川哲也

    medicina   Vol. 47 ( 3 ) page: 487-490   2010.3

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  57. [A case of metastatic pancreatic cancer with a remarkable response to combination therapy of gemcitabine and adoptive immune cell therapy]. Reviewed

    Norihiro Imai, Kinichi Takeda, Setsuo Utsunomiya, Masahiro Taga, Noboru Kawata, Takashi Ikeda, Yoshitaka Mizutani, Ken Hirose, Tetsuya Ishikawa, Shonen Yoshida

    Gan to kagaku ryoho. Cancer & chemotherapy   Vol. 37 ( 3 ) page: 527 - 9   2010.3

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    A 52-year-old woman with a chief complaint of epigastric distress was diagnosed as having pancreatic cancer with multiple liver metastases. After insertion of a metallic stent for biliary stenosis, combination therapy of gemcitabine (GEM) and adoptive immune cell therapy (AICT) was initiated. GEM 1,000 mg/m2 was administered on day 1, 8 and 15 every 4 weeks, while AICT using MUC1 peptide-pulsed dendritic cells (DC) and anti-CD3-activated T lymphocytes (CAT) was given biweekly. After 6 courses of GEM and 9 courses of DC-CAT, the patient was considered to have a complete response (CR) on CT and MRI examination. CR has still been maintained by the continuous administration of GEM and CAT. The combination therapy of GEM and AICT was suggested to be effective against advanced pancreatic cancer.

    PubMed

  58. Role of tumor necrosis factor-a in acute hepatitis B virus infection.

    ITO Hiroyasu, ANDO Kazuki, ISHIKAWA Tetsuya, SEISHIMA Mitsuru.

    Inflammation and Regeneration   Vol. 30 ( 5 ) page: 445 - 450   2010

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    Access below to see full text:
    http://www.jstage.jst.go.jp/article/inflammregen/30/5/445/_pdf

    DOI: 10.2492/inflammregen.30.445

  59. Interaction between LPS-induced NO production and IDO activity in mouse peritoneal cells in the presence of activated Va14 NKT cells. Reviewed

    Ohtaki H, Ito H, Ando K, Ishikawa T, Hoshi M, Tanaka R, Osawa Y, Yokochi T, Moriwaki H, Saito K, Seishima M.

    Biochem Biophys Res Com   Vol. 389 ( 2 ) page: 229-234   2009.11

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  60. Inflammatory cytokines modulate chemokine production patterns of HepG2 cells toward initially inclined direction. Reviewed

    Ohashi T, Tanabe J, Ishikawa T, Okumura A, Sato K, Ayada M, Hotta N, Kuzuya K, Ito H, Nakao H, Yoneda M, Kakumu S.

    Hepatol Res   Vol. 39 ( 5 ) page: 510-519   2009.5

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  61. V alpha14 NKT cells activated by alpha-galactosylceramide augment lipopolysaccharide-induced nitric oxide production in mouse intra-hepatic lymphocytes. Reviewed

    Ohtaki H, Ito H, Ando K, Ishikawa T, Saito K, Imawari M, Yokochi T, Moriwaki H, Seishima M

    Biochem Biophys Res Com   Vol. 378 ( 3 ) page: 579-583   2009.1

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  62. Role of TNF-alpha produced by nonantigen-specific cells in a fulminant hepatitis mouse model. Reviewed

    Ito H, Ando K, Ishikawa T, Saito K, Takemura M, Imawari M, Moriwaki H, Seishima M.

    J Immunol   Vol. 182 ( 1 ) page: 391-397   2009.1

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  63. Usefulness of radiofrequency ablation with micro-convex probe for hepatocellular carcinoma. Reviewed

    HOTTA Naoki, AYADA Minoru, MATSUMOTO Eiji, OKUMURA Akihiko, ISHIKAWA Tetsuya, SATO Ken, OOHASHI Tomohiko, KAKUMU Shinichi

    Hepato-gastroenterology   Vol. 56 ( 93 ) page: 1127-1132   2009

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    Background/Aims: It was aimed to assess whether a micro-convex probe is superior to the present conventional probe for ultrasonography from the points of safety and efficacy during percutaneous radiofrequency ablation therapy for hepatocellular carcinoma. Methodology: Twenty-one patients with 23 hepatocellular carcinoma lesions who had one or 2 lesions, each 4 cm or less in diameter, and liver function of Child-Pugh class A or B were enrolled. All the patients except for 2 patients were seropositive for hepatitis C virus. Radiofrequency ablation was carried out under a real-time US guidance. The cooled-tip electrodes used were single and clustered. Results: It was possible to perform safe and accurate percutaneous radiofrequency ablation procedure using micro-convex probes for the treatment of all hepatocellular carcinoma nodules. It was also possible to treat hepatocellular carcinoma located in the right subphrenic region without artificial pleural effusion under intercostal ultrasonography guide. Improved clustered needles were successfully applied to treat the nodules more than 3 cm in diameter with less resistance for penetration compared with the conventional needle. The findings of advanced dynamic flow image on ultrasonography to assess the therapeutic efficacy indicated the consistency with those of dynamic CT which was done 3 to 5 days later radiofrequency ablation. Major complication of radiofrequency ablation procedure was noted in none. Conclusions: These results suggest that micro-convex probe with clustered tips is superior to conventional probe for ultrasonography from the points of safety and efficacy during radiofrequency ablation for hepatocellular carcinoma nodule located in the right subphrenic region and for larger sized nodule more than 3 cm.

  64. A patient with Gilbert's syndrome complicated with drug-induced liver injury by the over-the-counter drug and Fluvastatin Sodium: A case report Reviewed

    Minoru Ayada, Tetsuya Ishikawa, Akihiko Okumura, Naoki Hotta, Akinori Hirose, Kazuo Masuko, Shinichi Kakumu

    Acta Hepatologica Japonica   Vol. 50 ( 3 ) page: 139 - 144   2009

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:The Japan Society of Hepatology  

    A 56-year-old female was admitted to our hospital because of epigastralgia, vomiting, hyperbilirubinemia, and abnormalities in the hepatic function tests. After the discontinuation of an over-the-counter drug, her symptoms and the abnormalities in the blood tests were improved. Thus she was diagnosed as drug-induced liver injury by the over-the-counter drug. The second episode of drug-induced liver injury occurred when she took Fluvastatin Sodium for her hyperlipemia. The liver injury was improved by the discontinuation of the drug
    however, only serum indirect bilirubin level remained abnormal. She was suspected to have constitutional jaundice, and diagnosed as Gilbert's syndrome by the analysis of gene polymorphism for UDP-glucuronyl transferase (UGT1A1). The polymorphism of UGT1A1 affects the efficiency of the lipophilic drug metabolism, and the activity of UGT1A1 is known to be low in the patients with Gilbert's syndrome Therefore the present case suggests that the recurrent drug-induced liver injury might be related to the low UGT1A1 activity due to Gilbert's syndrome. We here report the case with Gilbert's syndrome complicated with the recurrent drug-induced liver injuries. © 2009 The Japan Society of Hepatology.

    DOI: 10.2957/kanzo.50.139

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  65. Deficiency of forkhead box P3 and cytotoxic T-lymphocyte-associated antigen-4 gene expressions and impaired suppressor function of CD4+CD25+ T cells in patients with autoimmune hepatitis

    OKUMURA Akihiko, ISHIKAWA Tetsuya, SATO Sayaka, YAMAUCHI Taeko, OSHIMA Hisae, OHASHI Tomohiko, SATO Ken, AYADA Minoru, HOTTA Naoki, KAKUMU Shinichi

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 38 ( 9 ) page: 896 - 903   2008.9

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  66. Deficiency of forkhead box P3 and cytotoxic T-lymphocyte-associated antigen-4 gene expressions and impaired suppressor function of CD4+CD25+ T cells in patients with autoimmune hepatitis. Reviewed

    Okumura A, Ishikawa T, Sato S, Yamauchi T, Oshima H, Ohashi T, Sato K, Ayada M, Hotta N, Kakumu S.

    Hepatol Res   Vol. 38 ( 9 ) page: 896-903   2008.9

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  67. Role of V alpha14+ NKT cells in the development of hepatitis B virus-specific CTL: Activation of V alpha14+ NKT cells promotes the breakage of CTL tolerance. Reviewed

    Ito H, Ando K, Ishikawa T, Nakayama T, Taniguchi M, Saito K, Imawari M, Moriwaki H, Yokochi T, Kakumu S, Seishima M.

    Int Immunol   Vol. 20 ( 7 ) page: 869-879   2008.7

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  68. Use of the Model for End-Stage Liver Disease (MELD) score to predict 1-year survival of Japanese patients with cirrhosis and to determine who will benefit from living donor liver transplantation. Reviewed

    Ishigami M, Honda T, Okumura A, Ishikawa T, Kobayashi M, Katano Y, Fujimoto Y, Kiuchi T, Goto H.

    J Gastroenterol   Vol. 43 ( 5 ) page: 363-368   2008.5

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  69. Upregulation of indoleamine 2,3-dioxygenase in hepatocyte during acute hepatitis caused by hepatitis B virus-specific cytotoxic T lymphocytes in vivo. Reviewed

    Iwamoto N, Ito H, Ando K, Ishikawa T, Hara A, Taguchi A, Saito K, Takemura M, Imawari M, Moriwaki H, Seishima M.

    Liv Int   Vol. 29 ( 2 ) page: 277-283   2008.2

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  70. Use of hepatitis B vaccine for the treatment of chronic hepatitis B

    ISHIKAWA Tetsuya, KAKUMU Shinichi

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 37   page: S347 - S350   2007.10

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  71. Expression of Toll-like receptors in chronic hepatitis C virus infection. Reviewed

    Sato K, Ishikawa T, Okumura A, Yamauchi T, Sato S, Ayada M, Matsumoto E, Hotta N, Ohashi T, Fukuzawa Y, Kakumu S.

    J Gastroenterol Hepatol   Vol. 22 ( 10 ) page: 1627-1632   2007.10

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  72. Use of HB vaccine for the treatment of chronic hepatitis B. Invited

    Ishikawa T, Kakumu S.

    Hepatol Res   Vol. 37 ( S3 ) page: S347-S350   2007.10

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  73. Effect of Vitamin K2 on the recurrence in patients with hepatocellular carcinoma. Reviewed

    Hotta N, Ayada M, Sato K, Ishikawa T, Okumura A, Matsumoto E, Ohashi T, Kakumu S.

    Hepato-gastroenterology   Vol. 54 ( 79 ) page: 2073-2077   2007.10

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  74. 今月の主題 消化器薬の使い方Update 消化器疾患の薬物治療 自己免疫性肝炎(AIH)

    石川 哲也

    medicina   Vol. 44 ( 9 ) page: 1713 - 1715   2007.9

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    DOI: 10.11477/mf.1402102933

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  75. Double filtration plasmapheresis and interferon combination therapy for chronic hepatitis C patients with genotype 1 and high viral load

    FUJIWARA Kenji, KANEKO Shuichi, KAKUMU Shinichi, SATA Michio, HIGE Shuhei, TOMITA Eiichi, MOCHIDA Satoshi, IDE T., NISHIDA H., YOKOYAMA H., YAMASHITA T., MORIWAKI H., NAGAKI M., SUGIHARA J., TAKAHASHI H., ISHIKAWA T., MIYATA M., NISHIKAWA K., NAGOSHI S., SUGAHARA S., YAMAMOTO K., MIZUTA T., ANDO T., TAKEI Y., ENOMOTO N., TSUDA H., SUMINO Y., ISHII K., SAISHO H., YOKOSUKA O., EGUCHI K., HAMASAKI K., SAWADA K., FUKUNAGA K., ARAKAWA Y., MORIYAMA M., IMAWARI M., ITO T.

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 37 ( 9 ) page: 701 - 710   2007.9

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  76. Combination therapy with lamivudine and HB vaccine on chronic hepatitis B

    ISHIKAWA Tetsuya, KAKUMU Shinichi

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 37   page: S62 - S66   2007.7

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  77. Combination thearpy with lamivudine and HB vaccine on chronic heaptitis B. Invited

    Ishikawa T, Kakumu S.

    Hepatol Res   Vol. 37 ( S1 ) page: S62-S66   2007.7

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  78. 今月の主題 ウイルス肝炎 実地診療A to Z 扉

    石川 哲也

    medicina   Vol. 44 ( 5 ) page: 847 - 847   2007.5

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    DOI: 10.11477/mf.1402102722

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  79. 今月の主題 ウイルス肝炎 実地診療A to Z 座談会 外来で診るウイルス肝炎-効果的な病診連携のために

    八橋 弘, 伊東 和樹, 柴田 実, 石川 哲也

    medicina   Vol. 44 ( 5 ) page: 972 - 983   2007.5

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    DOI: 10.11477/mf.1402102753

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  80. 今月の主題 ウイルス肝炎 実地診療A to Z ウイルス肝炎の的確な診断のために 肝障害患者の診断の進め方

    各務 伸一, 石川 哲也

    medicina   Vol. 44 ( 5 ) page: 848 - 851   2007.5

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    DOI: 10.11477/mf.1402102723

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  81. Usefulness of a Bloodflow Diagnosis at Liver Tumors Using Sonazoid

    AYADA Minoru, HOTTA Naoki, OKUMURA Akihiko, ISHIKAWA Tetsuya, KIBA Kumiko, KURODA Yasuko, NIWA Sachiyo, IDO Makoto, KAKUMU Sinichi

      Vol. 34   2007.4

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  82. Four-Dimensional Ultrasonography for Therapeutic Radiofrequency Ablation for Hepatocellular Carcinoma

    HOTTA Naoki, AYADA Minoru, HIJIKATA Yasutaka, OOHASHI Tomohiko, SATO Ken, OKUMURA Akihiko, ISHIKAWA Tetsuya, OONO Nagayuki, KAKUMU Shinichi

      Vol. 34   2007.4

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  83. Usefulness of ultrasonography to Liver Tumor in Live 3D

    HOTTA Naoki, AYADA Minoru, OOHASHI Tomohiko, SATO Ken, OKUMURA Akihiko, ISHIKAWA Tetsuya, KOSAKI Masahiro, KAKUMU Shinichi

      Vol. 34   2007.4

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  84. Effect of vitamin K2 on the recurrence in patients with hepatocellular carcinoma

    Hotta Naoki, Ayada Minoru, Sato Ken, Ishikawa Tetsuya, Ohumura Ahihiko, Matsumoto Eiji, Ohashi Tomohiko, Kakumu Shinichi

    HEPATO-GASTROENTEROLOGY   Vol. 54 ( 79 ) page: 2073 - 2077   2007

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  85. Management of imatinib mesilate (IM)-related hepatic injury by adjusting the dose of the drug in a patient with chronic myelogenous leukemia (CML): A case report

    Ayada Minoru, Ishikawa Tetsuya, Okumura Akihiko, Hotta Naoki, Furuta Keiko, Yamauchi Taeko, Hijikata Yasutaka, Ohashi Tomohiko, Sato Ken, Kakumu Shinichi

    Kanzo   Vol. 48 ( 10 ) page: 505 - 510   2007

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    A 72-year-old female, with chronic myelogenous leukemia (CML) treated successfully with 400mg/day of imatinib mesilate (IM), developed laboratory signs of a cholestatic type of liver injury after one-year administration of IM, and was admitted to our hospital. We decided to stop the administration of IM to the patient. Thereafter the abnormalities in liver function tests recovered to the normal level promptly. However, with a necessity to use IM for preventing the recurrence of CML, we re-started administration of IM at a lower dose, by weighing the risk for liver injury and the benefit for CML in a balance. With careful monitoring of liver function tests, the dose of IM was gradually increased and reached 300mg/d, and the recurrence of liver injury or CML has not been observed. Here, we report the case of IM-related liver injury, controlled well after the re-administration of IM with the lower dose.<br>

    DOI: 10.2957/kanzo.48.505

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  86. A CASE OF HEMORRHAGIC GASTRIC VASCULAR ECTASIA TO BE ACCOMPANIED BY IDIOPATHIC PULMONARY FIBROSIS : SUCCESSFULLY TREATED BY ENDOSCOPIC BAND LIGATION

    AYADA Minoru, NAKANO Tatsunori, HOTTA Naoki, OKUMURA Akihiko, ISHIKAWA Tetsuya, OHASHI Tomohiko, MATSUMOTO Eiji, SATO Ken, YOSIDA Kagumi, KAKUMU Shinichi

    Gastroenterol Endosc   Vol. 48 ( 11 ) page: 2626 - 2631   2006.11

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  87. Role of toll-like receptors in hepatitis C virus-infected chronic liver disease

    Kakumu Shinichi, Okumura Akihiko, Ishikawa Tetsuya, Yamauchi Taeko, Sato Sayaka, Sato Ken, Ohashi Tomohiko, Ayada Minoru, Hotta Naoki, Fukuzawa Yoshitaka

    HEPATOLOGY   Vol. 44 ( 4 ) page: 300A - 300A   2006.10

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  88. Efficacy of non-invasive hepatic fibrosis quantificated-evaluation by liver elasticity measurement in nonalcoholic steatohepatitis (NASH) - Comparison of ultrasonic transient elastography and histopathological diagnosis

    Fukuzawa Yoshitaka, Kizawa Senji, Ohashi Tomohiko, Matsumoto Eiji, Sato Ken, Ayada Minoru, Hotta Naoki, Okumura Akihiko, Ishikawa Tetsuya, Kakumu Shinichi

    HEPATOLOGY   Vol. 44 ( 4 ) page: 649A - 650A   2006.10

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  89. Expression of toll-like receptor family on regulatory T cells in the patients with autoimmune hepatitis

    Okumura Akihiko, Ishikawa Tetsuya, Sato Sayaka, Yamauchi Taeko, Ohashi Tomohiko, Sato Ken, Ayada Minoru, Hotta Naoki, Fukuzawa Yoshitaka, Kakumu Shinichi

    HEPATOLOGY   Vol. 44 ( 4 ) page: 640A - 641A   2006.10

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  90. Four-dimensional ultrasonography for therapeutic radiofrequency ablation for heaptocellular carcinoma. Reviewed

    Hotta N, Maeno T, Ayada M, Sato K, Ishikawa T, Okumura A, Matsumoto E, Fukuzawa Y, Kakumu S.

    Hepato-gastroenterology   Vol. 53 ( 70 ) page: 521-525   2006.7

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  91. TRIALS OF PERCUTANEOUS ENDOSCOPIC GASTROSTOMY BY TRANSNASAL ENDOSCOPY USING A SMALL-CALIBER ENDOSCOPE

    AYADA Minoru, NAKANO Tatsunori, HOTTA Naoki, NAKAE Harumichi, KUNII Shin, YOSHIDA Kagumi, OKUMURA Akihiko, ISHIKAWA Tetsuya, FUKUZAWA Yoshitaka, KAKUMU Shinichi

    GASTROENTEROLOGICAL ENDOSCOPY   Vol. 48 ( 7 ) page: 1425 - 1430   2006.7

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    We performed percutaneous endoscopic gastrostomy (PEG) by transnasal endoscopy using a small-caliber endoscope for the purpose of relieving the pain and stress of gastrointestinal endoscopy and PEG without conscious cedation. The usefulness and safety were compared between cases performed PEG by transnasal endoscopy and those by transoral endoscopy. Cases with dysphagia by neurological diseases were divided into two groups randomly. The pull technique was used for both groups. We observed vital signs etc to compare pain and stress in transnasal insertion group and transoral insertion group. An increase in blood pressure and pulse rate was significantly small during PEG in the transnasal insertion group compared to the transoral group. There was no major complication in the transnasal insertion group as well as the transoral group. Our experience suggested that PEG by transnasal endoscopy using a smallcaliber endoscope is more useful than PEG by transoral endoscopy to relieve the pain and stress, and PEG by transnasal endoscopy is a safe method as well as PEG by transoral endoscopy.

    DOI: 10.11280/gee1973b.48.1425

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  92. Alteration of serum cytokine balances among different phases of chronic hepatitis B virus infection. Reviewed

    Ayada M, Ishikawa T, Okumura A, Tanabe J, Ito H, Ohashi T, Matsumoto E, Sato K, Hotta N, Fukuzawa Y, Kakumu S.

    Hepatol Res   Vol. 34 ( 4 ) page: 214-221   2006.4

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  93. 慢性肝疾患の病態にせまる免疫学的アプローチ 自己免疫性肝炎(AIH)における制御性T細胞(Tr)の機能低下

    奥村 明彦, 石川 哲也, 伊藤 弘康, 佐藤 さやか, 山内 妙子, 大橋 知彦, 松本 英司, 佐藤 顕, 綾田 穣, 堀田 直樹, 福澤 嘉孝, 各務 伸一

    消化器と免疫   Vol. 42 ( 42 ) page: 29 - 32   2006.4

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    自己免疫性肝炎患者の制御性T細胞(Tr)について,Trの機能を調節しているFoxp3,TNF-R-SF18,CTLA-4,CD28の各遺伝子の発現を調べ調べ,自己免疫性肝炎(AIH)患者と健常者のTrのサイトカイン産生能を比較し,TrがAIHの病態に関与している可能性について検討した.AIH 15例,コントロールとしてC型慢性肝炎(CH-C)患者26例と健常人12例を対象とした.AIHではFoxp3,CTLA-4のmRNA量が減少し,TrによるIL-10の産生能が低下していることが明らかとなった.Trの機能異常が病態に関与している可能性が示唆された

  94. Plasma amino acid profiles applied for diagnosis of advanced liver fibrosis in patients with chronic hepatitis C infection. Reviewed

    Zhang Q, Takahashi M, Noguchi Y, Sugimoto T, Kimura T, Okumura A, Ishikawa T, Kakumu S.

    Hepatol Res   Vol. 34 ( 3 ) page: 170-177   2006.3

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  95. The SHAP-hyaluronan complex in serum from patients with chronic liver diseases caused by hepatitis virus infection. Reviewed

    Shen L, Zhuo L, Okumura A, Ishikawa T, Miyachi M, Owa Y, Ishizawa T, Sugiura N, Nagata Y, Nonami T, Kakumu S, Kimata K.

    Hepatol Res   Vol. 34 ( 3 ) page: 178-186   2006.3

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  96. 肝癌局所療法における超音波ドプラ法の新展開 Real Time 4D Ultrasoundを用いた肝細胞癌のラジオ波焼灼療法の有用性-マイクロコンベックスプローブ使用における検討も含めて

    堀田 直樹, 大橋 知彦, 松本 英司, 佐藤 顕, 綾田 穣, 奥村 明彦, 石川 哲也, 福沢 嘉孝, 各務 伸一

    Rad Fan   Vol. 4 ( 3 ) page: 116 - 119   2006.2

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    従来の2D modeのエコーではなく,Real Time 4D Ultrasound systemsを用いて肝細胞癌に対しラジオ波焼灼療法(RFA)を施行し,その有用性について検討した.また,マイクロコンベックスプローブにおいても検討した.肝細胞癌22例25結節を対象とした.RFA施行22例25結節において,全症例Real Time 4D Ultrasound systemにて穿刺可能であった.Real Time 4D Ultrasound使用によるRFAは多方向より針の留置部位を確認することができ,より正確に経皮的治療を施行することができた

  97. Cholestatic hepatic injury related to administration of sodium risedronate hydrate. A case report with distinctive histological findings

    AYADA Minoru, ISHIKAWA Tetsuya, OKUMURA Akihiko, OHASHI Tomohiko, MATSUMOTO Eiji, SATO Ken, HOTTA Naoki, FUKUZAWA Yoshitaka, KAKUMU Shinichi

    Kanzo   Vol. 47 ( 1 ) page: 10 - 15   2006.1

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    A 53-year-old woman was hospitalized because of general fatigue, jaundice, and the elevation of serum hepatic and biliary enzymes. She was suffering from osteoporosis, and had undergone treatment with oral administration of sodium risedronate hydrate (SRH) for 6 months before admission. Liver injury related to SRH was suspected, and the medication was stopped. After cessation of the medication, she recovered from her illness, and the elevated enzymes gradually declined. According to the diagnostic scale for drug-induced hepatic injury at the workshop in Digestive Disease Week-Japan 2004, her liver injury was classified into cholestatic type and judged “highly possible.” Liver biopsy showed the distinctive findings, such as diffuse rosette formations of hepatocytes in liver parenchyma, and strongly supported the diagnosis.<br>Liver biopsy gives us important, sometimes critical information as the present case, thus it should be considered for execution as an auxiliary measure for accurate diagnosis of drug-related liver injury.

    DOI: 10.2957/kanzo.47.10

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  98. Four-dimensional ultrasonography for therapeutic radiofrequency ablation for hepatocellular carcinoma

    Hotta Naoki, Maeno Tadashi, Ayada Minoru, Sato Ken, Ishikawa Tetsuya, Okumura Akihiko, Matsumoto Eiji, Fukuzawa Yoshitaka, Kakumu Shinichi

    HEPATO-GASTROENTEROLOGY   Vol. 53 ( 70 ) page: 521 - 525   2006

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  99. Rebamipide enemas-New effective treatment for patients with corticosteroid dependent or resistant ulcerative colitis-

    Miyata M, Kasugai K, Ishikawa T, Kakumu S, Onishi M, Mori T.

    Dig Dis Sci   Vol. 50 ( S1 ) page: S119-S123   2005.10

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  100. Assessment of hepatic fibrosis in chronic liver disease - Usefulness of the strain rate imaging method

    Hotta N, Okumura A, Ishikawa T, Kakumu S

    HEPATOLOGY   Vol. 42 ( 4 ) page: 342A - 342A   2005.10

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  101. 出血性胃vascular ectasiaに対し内視鏡的結紮術が有効であった2例

    綾田 穣, 堀田 直樹, 石川 哲也, 奥村 明彦, 恒川 明久, 井澤 晋也, 大橋 知彦, 松本 英司, 佐藤 顕, 福沢 嘉孝, 各務 伸一

    Gastroenterological Endoscopy   Vol. 47 ( Suppl.2 ) page: 1971 - 1971   2005.9

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  102. Four-dimensional ultrasonogaraphy for therapeutic radiofrequency ablation for hepatocellular carcinoma

    Hotta N, Okumura A, Ishikawa T, Fukuzawa Y, Kakumu S

    AMERICAN JOURNAL OF GASTROENTEROLOGY   Vol. 100 ( 9 ) page: S106 - S106   2005.9

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  103. 門脈圧亢進症の新しい薬物療法 難治性腹水に対するdocarpamineの有用性と安全性

    綾田 穣, 石川 哲也, 堀田 直樹, 奥村 明彦, 大橋 知彦, 松本 英司, 佐藤 顕, 福沢 嘉孝, 各務 伸一

    日本門脈圧亢進症学会雑誌   Vol. 11 ( 1 ) page: 43 - 43   2005.7

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  104. B型肝炎ウイルス(HBV)関連抗原が肝炎進展過程に与える影響について

    佐藤 顕, 石川 哲也, 田邊 純一, 大橋 知彦, 松本 英司, 前野 禎, 綾田 穣, 堀田 直樹, 宮田 充樹, 奥村 明彦, 福沢 嘉孝, 各務 伸一

    消化器と免疫   Vol. 41 ( 41 ) page: 159 - 162   2005.5

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    標題の影響を明らかにするため,concanavalin A(Con A)を投与されたHBVトランスジェニックマウスの肝臓におけるサイトカイン,ケモカインの発現パターンを解析し,同系正常マウスと比較した.結果,トランスジェニックマウスではCon A投与後2時間から24時間にかけてIL-18,TGF-β,GM-CSF,fractalkineの発現が正常マウスよりも強く,24時間後にはTNF-αとINF-γの発現が強かった.これは,HBV関連抗原が免疫応答を制御あるいは修飾することで何らかの免疫異常を引き起こしている可能性を示すと考えられた

  105. Changes in natural killer T cells subsets during therapy in type C hepatitis and hepatocellular carcinoma. Reviewed

    Okumura A, Ishikawa T, Maeno T, Sato K, Ayada M, Hotta N, Yamauchi T, Fukuzawa Y, Kakumu S.

    Hepatol Res   Vol. 32 ( 4 ) page: 213-217   2005.4

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  106. マイクロコンベックス使用におけるラジオ波焼灼療法の経験

    堀田 直樹, 綾田 穣, 佐藤 顕, 松本 英司, 奥村 明彦, 石川 哲也, 福沢 嘉孝, 高橋 忍, 各務 伸一

    超音波医学   Vol. 32 ( Suppl. ) page: S409 - S409   2005.4

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  107. A CASE OF HEMORRHAGIC DUODENAL VASCULAR ECTASIA : SUCCESSFULLY TREATED BY ENDOSCOPIC VARICEAL LIGATION

    AYADA Minoru, FUKUZAWA Yoshitaka, HOTTA Naoki, MATSUMOTO Eiji, MAENO Tadashi, SATO Ken, OKUMURA Akihiko, ISHIKAWA Tetsuya, KAKUMU Shinichi

    Gastroenterol Endosc   Vol. 47 ( 1 ) page: 15 - 21   2005.1

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  108. Advanced dynamic flow imaging with contrast-enhanced ultrasonography for the evaluation of tumor vascularity in liver tumors. Reviewed

    Hotta N, Tagaya T, Maeno T, Ayata M, Sato K, Ishikawa T, Okumura A, Fukuzawa Y, Kakumu S.

    Clin Imaging   Vol. 29 ( 1 ) page: 34-41   2005.1

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  109. A CASE OF HEMORRHAGIC DUODENAL VASCULAR ECTASIA: SUCCESSFULLY TREATED BY ENDOSCOPIC VARICEAL LIGATION

    AYADA Minoru, FUKUZAWA Yoshitaka, HOTTA Naoki, MATSUMOTO Eiji, MAENO Tadashi, SATO Ken, OKUMURA Akihiko, ISHIKAWA Tetsuya, KAKUMU Shinichi

    GASTROENTEROLOGICAL ENDOSCOPY   Vol. 47 ( 1 ) page: 15 - 21   2005.1

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    A 82-year-old-woman was hospitalized because of the hemorrhagic small intestinal an-giodysplasia with general malaise. On emergent gastrointestinal fiberscopy, we formed a duodenal vascular ectasia with two bleeding spots among several vascular ectasia at the superior duodenal angle. We successfully treated the two hemorrhagic vascular ectasia using a ligating device for endoscopic variceal ligation (EVL). Permanent hemostasis was obtained with one procedure with out side effects. EVL appeared to be useful for small hemorrhagic lesions of small intestine.

    DOI: 10.11280/gee1973b.47.15

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  110. A case of hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) using 4D real-time ultrasound system

    Hotta N, Fukuzawa Y, Ayada M, Sato K, Maeno T, Tagaya T, Okumura A, Ishikawa T, Ito Y, Kakumu S

    HEPATO-GASTROENTEROLOGY   Vol. 52 ( 64 ) page: 1224-1227   2005

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  111. 【内科診療最前線2005 この1年の動向を踏まえて】 肝疾患

    各務 伸一, 福沢 嘉孝, 石川 哲也, 奥村 明彦, 堀田 直樹, 綾田 穣

    内科   Vol. 94 ( 6 ) page: 1030 - 1038   2004.12

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    DOI: 10.15106/j00974.2005057442

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  112. 【内科診療最前線2005 この1年の動向を踏まえて】肝疾患

    各務 伸一, 福沢 嘉孝, 石川 哲也, 奥村 明彦, 堀田 直樹, 綾田 穣

    内科   Vol. 94 ( 6 ) page: 1030 - 1038   2004.12

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  113. Usefulness of contrast-enhanced ultrasonography to evaluate therapeutic effects for hepatocellular carcinoma

    Hotta N, Okumura A, Ishikawa T, Kakumu S

    AMERICAN JOURNAL OF GASTROENTEROLOGY   Vol. 99 ( 10 ) page: S69 - S69   2004.10

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  114. Dynamics of CD8(+)T cells, CD4(+)T cells, and CD4(+)CD25(+) regulatory T cells in the liver with autoimmune hepatitis(AIH) - Analysis using mice model for AIH type 2

    Okumura A, Ishikawa T, Ito H, Sato K, Maeno T, Ayada M, Hotta N, Matsumoto E, Ohashi T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 40 ( 4 ) page: 421A - 421A   2004.10

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  115. Nutrition assessment and management in outpatients with liver cirrhosis caused by HCV (LC-C) - Usefulness of a branched chain amino acid (BCAA)-rich product as late evening snacks (LES)

    Fukuaawa Y, Hotta N, Ayada M, Ohashi T, Matsumoto E, Sato K, Maeno T, Okumura A, Ishikawa T, Kakumu S

    HEPATOLOGY   Vol. 40 ( 4 ) page: 512A - 512A   2004.10

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  116. 2) DFPPによるウイルス除去療法 : DFPPによるC型肝炎ウイルス減量療法の効果(日本アフェレシス学会第13回関東甲信越地方会抄録)

    西川 和裕, 宮田 充樹, 奥村 明彦, 石川 哲也, 各務 伸一

    日本アフェレシス学会雑誌   Vol. 23 ( 3 ) page: 289-290   2004

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  117. 内科診療最前線2005-この1年の動向を踏まえて-非アルコール性脂肪性肝炎 (NASH),アルコール性肝障害 (ALD). Reviewed

    各務伸一, 福沢嘉孝, 石川哲也, 奥村明彦, 堀田直樹, 綾田穣

    内科   Vol. 94   page: 1823 - 1829   2004

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  118. Successful treatment of gastric fundal varices by balloon-occluded retrograde transvenous obliteration (B-RTO) for a patient with Wilson disease Reviewed

    Japanese Journal of Portal Hypertension   Vol. 10 ( 10 ) page: 132 - 136   2004

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    DOI: 10.11423/jsph1999.10.3-4_132

  119. Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic heaptitis C virus infection. Reviewed

    Maeno T, Okumura A, Ishikawa T, Kato K, Sakakibara F, Sato K, Ayada M, Hotta N, Tagaya T, Fukuzawa Y, Kakumu S.

    J Gastroenterol Hepatol   Vol. 18 ( 12 ) page: 1358-1363   2003.12

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  120. 生活習慣病を合併した著明な脂肪肝症例に対して茵ちん蒿湯・防風通聖散併用療法が奏効した1例

    福沢 嘉孝, 堀田 直樹, 佐藤 顕, 前野 禎, 綾田 穣, 多賀谷 恒明, 奥村 明彦, 石川 哲也, 各務 伸一, 加藤 勝久

    漢方医学   Vol. 27 ( 5 ) page: 221 - 224   2003.12

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    53歳女.全身倦怠感,後頭部不快感を主訴とした.身長161cm,体重81kg,普段から暑がりで便秘傾向があり,熱実証,腹壁が厚く弾力があった.臨床データは異常値を示し,臨床データ及び腹部超音波検査より,高脂血症,高血圧,肥満,耐糖能障害(IGT)を合併する著明な脂肪肝と診断した.高血圧にはアンジオテンシンII受容体拮抗薬バルサルタンを投与し,コントロール良好となった.肥満・高脂血症・脂肪肝・IGTに対しては食事・運動療法を開始したが,各種データの改善は乏しかった.その後,生活習慣の乱れによりデータが悪化し,体重も治療前値付近に戻ったため,従来法を継続しながら,茵ちん蒿湯を新たに処方し,強化療法も同時に行った.約5ヵ月後,各種データは改善傾向を示したが,体重は殆ど変化しなかった.患者が減量を切望したこと等より,10月末から防風通聖散を併用した.治療開始から漢方薬併用投与約3.5ヵ月後迄に体重は74kgになり,各種データも改善し,自覚症状も殆ど消失した.現在,大きな副作用は認めず,生活習慣病に対する病識も向上してきた.従来法は継続中である

  121. Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection

    Maeno T, Okumura A, Ishikawa T, Kato K, Sakakibara F, Sato K, Ayada M, Hotta N, Tagaya T, Fukuzawa Y, Kakumu S

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   Vol. 18 ( 12 ) page: 1358 - 1363   2003.12

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  122. Usefulness of contrast-enhanced ultrasonography with dynamic flow imaging to evaluated therapeutic effects for hepatocellular carcinoma. Reviewed

    Hotta N, Tagaya T, Maeno T, Ishikawa T, Okumura A, Fukuzawa Y, Kakumu S.

    Hepato-gastroenterology   Vol. 50 ( 54 ) page: 1867-1871   2003.11

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  123. Combination therapy of lamivudine and HB vaccine for the treatment of chronic hepatitis B.

    Ishikawa T, Okumura A, Maeno T, Sato K, Ayada M, Hotta N, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 38 ( 4 ) page: 717A - 717A   2003.10

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  124. Establishment of a novel mouse model for AIH type 2.

    Okumura A, Ishikawa T, Sato K, Ayada M, Maeno T, Hotta N, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 38 ( 4 ) page: 485A - 485A   2003.10

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  125. Nutrition is more important than Th1-dominated condition for better response in interferon alpha-2b/ribavirin therapy.

    Okumura A, Ishikawa T, Ayada M, Sato K, Maeno T, Hotta N, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 38 ( 4 ) page: 314A - 314A   2003.10

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  126. Involvement of CD4+ CD25+ regulatory T cells as immune modulators in chronic hepatitis C virus (HCV) infection.

    Okumura A, Ishikawa T, Yamauchi T, Maeno T, Sato K, Ayada M, Hotta N, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 38 ( 4 ) page: 463A - 463A   2003.10

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  127. 肝細胞癌におけるFas/Fas Lの発現と浸潤リンパ球との関係

    福澤 嘉孝, 堀田 直樹, 佐藤 顕, 前野 禎, 綾田 穣, 多賀谷 恒明, 奥村 明彦, 石川 哲也, 各務 伸一

    愛知医科大学医学会雑誌   Vol. 31 ( 2 ) page: 106 - 107   2003.6

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  128. Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus. Reviewed

    Arao M, Murase K, Kusakabe A, Yoshioka K, Fukuzawa Y, Ishikawa T, Tagaya T, Yamanouchi K, Ichimiya H, Sameshima Y, Kakumu S.

    J Gastroenterol   Vol. 38 ( 4 ) page: 355-360   2003.4

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  129. Lack of tumor necrosis factor alpha induces impaired proliferation of hepatitis B virus-specific cytotoxic T lymphocytes. Reviewed

    Kasahara S, Ando K, Saito K, Sekikawa K, Ito H, Ishikawa T, Ohnishi H, Seishima M, Kakumu S, Moriwaki H.

    J Virol   Vol. 77 ( 4 ) page: 2469-2476   2003.2

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  130. Levels of SHAP-HA complex in the sera of patients with chronic liver diseases -Usefulness as an indicator for diagnosis of hepatocellular carcinoma-

    Shen L., Zhou L., Okumura A., Ishikawa T., Kakumu S., Kimata K.

    Japan Journal of Molecular Tumor Marker Research   Vol. 19 ( 19 ) page: 70 - 71   2003

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    DOI: 10.11241/jsmtmr.19.70

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  131. Usefulness of contrast-enhanced ultrasonography with dynamic flow imaging to evaluate therapeutic effects for hepatocellular carcinoma

    Hotta N, Tagaya T, Maeno T, Ishikawa T, Okumura A, Fukuzawa Y, Kakumu S

    HEPATO-GASTROENTEROLOGY   Vol. 50 ( 54 ) page: 1867 - 1871   2003

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  132. 3. B型慢性肝炎へのラミブジン+HBワクチン併用療法

    石川 哲也, 奥村 明彦, 各務 伸一

    肝臓   Vol. 43 ( 10 ) page: 470-471   2002.10

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  133. Usefulness of contrast-enhanced ultrasonography with dynamic flow imaging to evaluate therapeutic effects for hepatocelluiar carcinoma.

    Hotta N, Maeno T, Tagaya T, Ayata M, Satoh K, Okumura A, Fukuzawa Y, Ishikawa T, Kakumu S

    HEPATOLOGY   Vol. 36 ( 4 ) page: 687A - 687A   2002.10

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  134. Combination of HB vaccine with lamivudine for the treatment of chronic hepatitis B.

    Ishikawa T, Okumura A, Maeno T, Sato K, Ayada Y, Hotta N, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 36 ( 4 ) page: 643A - 643A   2002.10

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  135. Different distribution of antigenic B cell and T cell epitopes within HBV core region

    Okumura A, Ishikawa T, Sato K, Maeno T, Ayada M, Hotta N, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 36 ( 4 ) page: 620A - 620A   2002.10

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  136. Expression of glypican-3 (GPC 3) and its significance as a novel marker of the degree of dedifferentiation in hepatocellular carcinoma

    Fukuzawa Y, Furuta K, Tagaya T, Sato K, Maeno T, Ayada M, Hotta N, Okumura A, Ishikawa T, Kakumu S

    HEPATOLOGY   Vol. 36 ( 4 ) page: 691A - 691A   2002.10

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  137. 慢性肝疾患と免疫 B型慢性肝炎患者におけるHBc抗原領域のエピトープの同定とそれに対する免疫応答の質的解析

    石川 哲也, 田邊 純一, 佐藤 顕, 前野 禎, 綾田 穣, 堀田 直樹, 多賀谷 恒明, 奥村 明彦, 福沢 嘉孝, 各務 伸一

    消化器と免疫   ( 38 ) page: 20 - 23   2002.3

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    B型慢性肝炎患者(B-CH)におけるHBc抗原特異的免疫応答の標的部位の解析,免疫応答の質的評価を行った.B-CH患者23例を対象に,HBc抗原領域をカバーする13〜15merのペプタイドを作製し,患者末梢血単核球を刺激後,細胞内サイトカイン/ケモカイン発現パターンをflow cytometry(FACS)及びRT-PCRにて解析した.FACS解析では,HBc91-105(p19)での刺激時に,FN-γ+細胞,IL-4+細胞とも有意な増加がみられた.また,RT-PCRを用いた解析ではp19による刺激で11例中8例で,多くの場合,同時に複数のサイトカイン/ケモカインの発現増強がみられた.これらのことから,B-CH患者においてはp19に主要なエピトープが存在している可能性が示唆された

  138. Expression of Fas/Fas ligand (FasL) and its involvement in infiltrating lymphocytes in hepatocellular carcinoma (HCC)

    FUKUZAWA Yoshitaka, TAKAHASHI Kiyoshi, FURUTA Keiko, TAGAYA Tsuneaki, ISHIKAWA Tetsuya, WADA Kaori, OMOTO Yasukazu, KOJI Takehiko, KAKUMU Shinichi

    Journal of gastroenterology   Vol. 36 ( 10 ) page: 681 - 688   2001.10

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  139. Expression of Fas/Fas ligand (FasL) and its involvement in infiltrating lymphocytes in hepatocellular carcinoma (HCC). Reviewed

    Fukuzawa Y, Takahashi K, Furuta K, Tagaya T, Ishikawa T, Wada K, Omoto Y, Koji T, Kakumu S.

    J Gastroenterol   Vol. 36 ( 10 ) page: 178-186   2001.10

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  140. Expression of Fas/Fas ligand (FasL) and its involvement in infiltrating lymphocytes in hepatocellular carcinoma (HCC) Reviewed

    Y Fukuzawa, K Takahashi, K Furuta, T Tagaya, T Ishikawa, K Wada, Y Omoto, T Koji, S Kakumu

    JOURNAL OF GASTROENTEROLOGY   Vol. 36 ( 10 ) page: 681 - 688   2001.10

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    Background. This study was conducted to examine the expression of Fas/Fas ligand (FasL), to elucidate its relationship with tumor-infiltrating lymphocytes (TILs), and to detect possible gene mutation of Fas/FasL in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Methods. Indirect immunohistochemical staining was performed on formalin-fixed, paraffin-embedded sections of liver biopsy and surgery specimens from five normal livers, and from the livers of 30 patients with HCC. Fas/FasL mRNA-expressing cells and apoptotic cells were detected by in situ hybridization and DNA nick end labeling (TUNEL), respectively. We also performed polymerase chain reaction (PCR) -amplifying and direct sequencing for the Fas/FasL gene. Results. Fas/FasL and its mRNA were localized on the, membrane or in the cytoplasm in some HCC cells, as well as hepatocytes. Their expression was enhanced in areas with infiltrating inflammatory cells in the noncancerous regions of liver tissue and on the margins of the cancerous tissue. The positivity rate for TUNEL was elevated along these margins. The labeling index of Fas/FasL was lower in the cancerous liver tissue than in the surrounding noncancerous region (P &lt; 0.01), and tended to decrease in proportion to the malignancy of tumor cells; Fas/FasL expression was not found on poorly differentiated type cancer cells. Fas(-)/FasL(+), FasL-mRNA(+) HCC cells were seen in one specimen of moderately differentiated type. Some CD8+T lymphocytes were TUNEL-positive around the cancerous region. In this study, cancerous and noncancerous tissues in HCC revealed no genetic mutations in any exons of Fas/FasL. Conclusions. These findings suggest that Fas/FasL expression was decreased in proportion to the malignancy of tumor cells, and that infiltrating CD8+T lymphocytes play a role in apoptosis in HCC. The apoptosis in HCC could be regulated by the suppression of Fas/FasL expression, or, sometimes, by the enhancement of FasL expression.

    DOI: 10.1007/s005350170031

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  141. Expression of Fas/Fas ligand (FasL) and its involvement in infiltrating lymphocytes in hepatocellular carcinoma (HCC)

    Fukuzawa Y, Takahashi K, Furuta K, Tagaya T, Ishikawa T, Wada K, Omoto Y, Koji T, Kakumu S

    JOURNAL OF GASTROENTEROLOGY   Vol. 36 ( 10 ) page: 681 - 688   2001.10

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  142. Identification of highly immunogenic T cell epitope within HBV core region and immune response triggered by the activation of HBV core specific T cells.

    Ishikawa T, Tanabe J, Okumura A, Maeno T, Yamamoto K, Hotta N, Yoshida K, Ito M, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 34 ( 4 ) page: 312A - 312A   2001.10

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  143. Crosstalk between oxidative stress and apoptosis in hepatocellular carcinoma (HCC).

    Fukuzawa Y, Hotta N, Furuta K, Maeno T, Yamamoto K, Yoshida K, Ito M, Tagaya T, Okumura A, Ishikawa T, Kakumu S

    HEPATOLOGY   Vol. 34 ( 4 ) page: 515A - 515A   2001.10

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  144. Experimental autoimmune hepatitis in mice following immunization with cytochrome P450IID6.

    Ishikawa T, Tanabe JC, Okumura A, Ito M, Maeno T, Yamamoto K, Yoshida K, Hotta N, Tagaya T, Fukuzawa Y, Miyakawa H, Kakumu S

    HEPATOLOGY   Vol. 34 ( 4 ) page: 286A - 286A   2001.10

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  145. Increased insulin resistance in the patients with chronic HCV infection is mediated by elevated serum TNF alpha.

    Maeno T, Okumura A, Ishikawa T, Yamamoto K, Hotta N, Yoshida K, Ito M, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 34 ( 4 ) page: 552A - 552A   2001.10

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  146. Impaired function of peripheral blood dendritic cell subsets of hepatitis C virus-infected patients.

    Sobue S, Nomura T, Nakao H, Okumura A, Ishikawa T, Kakumu S, Itoh M

    HEPATOLOGY   Vol. 34 ( 4 ) page: 482A - 482A   2001.10

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  147. Th1/Th2 cytokine profiles and their relationship to clinical features in patients with chronic hepatitis C virus infection. Reviewed

    Sobue S, Nomura T, Ishikawa T, Ito S, Saso K, Ohara H, Joh T, Itoh M, Kakumu S.

    J Gastroenterol   Vol. 36 ( 8 ) page: 544-551   2001.8

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  148. 消化器疾患の病態とTh1/Th2バランス 肝細胞のケモカイン産生とTh1/Th2バランスへの影響

    石川 哲也, 田邊 純一, 伊東 正道, 奥村 明彦, 多賀谷 恒明, 福澤 嘉孝, 各務 伸一

    消化器と免疫   ( 37 ) page: 5 - 8   2001.7

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    肝細胞の炎症及びTh1/Th2 cytokine刺激に対する反応,その後のTh1/Th2バランスに与える影響を,肝細胞のchemokine産生を測定することにより検討した.肝細胞はIFN-γ(Th1)刺激により,更にTh1反応を促進する方向に働くこと,IL-4(Th2)刺激によりTh1反応を抑制し,Th2反応を間接的に促進する方向に働くことがわかった.IL-1O(Th2)刺激はTh2反応を間接的に促進する方向に働いた.肝炎においては肝細胞自身が免疫応答の方向性を制御している可能性が示された

  149. Apoptosis is induced by caspase activation and cytochrome c release in photodynamic therapy (PDT) of human hepatocellular carcinoma cells.

    Okumura A, Hamblin MR, Hasan T, Ishikawa T, Kakumu S, Takahashi H

    GASTROENTEROLOGY   Vol. 120 ( 5 ) page: A363 - A363   2001.4

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  150. 最近の癌の動向 当科における肝癌患者の実態

    福沢 嘉孝, 堀田 直樹, 前野 禎, 山本 賢一, 吉田 香果, 吉田 篤生, 伊東 正道, 多賀谷 恒明, 奥村 明彦, 石川 哲也

    愛知医科大学医学会雑誌   Vol. 29 ( 2 ) page: 148 - 150   2001.3

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  151. Mutation at codon 130 in hepatitis B virus (HBV) core region increases markedly during acute exacerbation of hepatitis in chronic HBV carriers. Reviewed

    Okumura A, Ishikawa T, Yoshioka K, Yuasa R, Fukuzawa Y, Kakumu S.

    J Gastroenterol   Vol. 36 ( 2 ) page: 103-110   2001.2

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  152. Update of liver disease related to chronic hepatitis B virus infection. Invited

    Ishikawa T, Kakumu S.

    Int Med   Vol. 40 ( 2 ) page: 178-179   2001.2

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  153. Symposium on Clinical Aspects in Hepatitis Virus Infection, Update of Liver Disease Related to Chronic Hepatitis B Virus Infection

    ISHIKAWA Tetsuya, KAKUMU Shinichi

    Internal medicine   Vol. 40 ( 2 ) page: 178 - 179   2001.2

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    DOI: 10.2169/internalmedicine.40.178

  154. 学会記”肝臓学会” Reviewed

    各務伸一, 福沢嘉孝, 石川哲也, 奥村明彦

    日本醫亊新報   ( 4033 ) page: 40 - 42   2001

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  155. Randomized controlled trial of twice-a-day administration of natural interferon β for chronic hepatitis C

    YOSHIOKA Kentaro, YANO Motoyoshi, HIROFUJI Hideo, ARAO Motohiro, KUSAKABE Atsuhiko, SAMESHIMA Yoichi, KURIKI Junsuke, KUROKAWA Susumu, MURASE Kenichi, ISHIKAWA Tetsuya, KAKUMU Shinichi

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 18 ( 3 ) page: 310 - 319   2000.11

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    Publishing type:Research paper (scientific journal)  

  156. Randomized controlled trial of twice-a-day administration of natural interferon beta for chronic hepatitis C. Reviewed

    Yoshioka K, Yano M, hirohuji H, Arao M, Kusakabe A, Sameshima Y, Kuriki J, Kurokawa S, Murase K, Ishikawa T, Kakumu S, IFN Treatment Group of Affiliated Hospitals of Third Department of Internal Medicine at Nagoya University School of Medicine.

    Hepatol Res   Vol. 18 ( 3 ) page: 310-319   2000.11

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  157. Roles of hepatocytes in regulating inflammatory reactions.

    Tanabe J, Ishikawa T, Ito M, Maeno T, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 32 ( 4 ) page: 202A - 202A   2000.10

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    Web of Science

  158. Association of chronic HCV infection and diabetes mellitus among Japanese populations.

    Kakumu S, Tagaya T, Fukuzawa Y, Ishikawa T, Arao M, Murase K, Kusakabe A, Yoshioka K

    HEPATOLOGY   Vol. 32 ( 4 ) page: 543A - 543A   2000.10

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    Web of Science

  159. Comparison of serum cytokine levels between type C cirrhotic patients with and without hepatocellular carcinoma.

    Ito M, Ishikawa T, Tanabe J, Hotta N, Yoshida K, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 32 ( 4 ) page: 620A - 620A   2000.10

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    Web of Science

  160. Influence of hepatitis B core protein and its defective mutants on growth and gene expression of hepatocytes.

    Tanabe J, Ishikawa T, Ito M, Yoshida A, Tagaya T, Fukuzawa Y, Kakumu S

    HEPATOLOGY   Vol. 32 ( 4 ) page: 393A - 393A   2000.10

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    Web of Science

  161. Decreased function of peripheral blood dendritic cell in patients with hepatocellular carcinoma with hepatitis B and C virus infection. Reviewed

    Kakumu S, Ito S, Ishikawa T, Mita Y, Tagaya T, Fukuzawa Y, Yoshioka K.

    J Gastroenterol Hepatol   Vol. 61 ( 1 ) page: 23-28   2000.5

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  162. Properties of hepatitis B virus genome recovered from Vietnamese patients with fulminant hepatitis in comparison with those from acute hepatitis. Reviewed

    Yuasa R, Takahashi K, Dien BV, Binh NH, Morishita T, Sato K, Yamamoto N, Isomura S, Yoshioka K, Ishikawa T, Mishiro S, Kakumu S.

    J Med Virol   Vol. 61 ( 1 ) page: 23-28   2000.5

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  163. Properties of hepatitis B virus genome recovered from Vietnamese patients with fulminant hepatitis in comparison with those of acute hepatitis

    Yuasa R, Takahashi B, Dien BV, Binh NH, Morishita T, Sato K, Yamamoto N, Isomura S, Yoshioka K, Ishikawa T, Mishiro S, Kakumu S

    JOURNAL OF MEDICAL VIROLOGY   Vol. 61 ( 1 ) page: 23 - 28   2000.5

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    Web of Science

  164. Decreased function of peripheral blood dendritic cells in patients with hepatocellular carcinoma with hepatitis B and C virus infection

    Kakumu S, Ito S, Ishikawa T, Mita Y, Tagaya T, Fukuzawa Y, Yoshioka K

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   Vol. 15 ( 4 ) page: 431 - 436   2000.4

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    Web of Science

  165. 肝炎ウイルスの臨床  3 B型慢性肝疾患の話題

    石川 哲也, 各務 伸一

    日本内科学会雑誌   Vol. 89 ( 9 ) page: 1845 - 1849   2000

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    DOI: 10.2169/naika.89.1845

    PubMed

    CiNii Research

  166. Elevated intracellular IFN-gamma levels in circulating CD8+ lymphocytes in patients with fulminant hepatitis. Reviewed

    Kimura K, Ando K, Ohnishi H, Tomita E, Muto Y, Moriwaki H, Ishikawa T, Kakumu S.

    J Hepatol   Vol. 31 ( 4 ) page: 579-583   1999.10

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  167. Immuno-pathogenesis of hepatic fibrosis in chronic liver injury induced by repeatedly administered concanavalin A. Reviewed

    Kimura K, Ando K, Ohnishi H, Takemura M, Muto Y, Moriwaki H, Ishikawa T, Kakumu S.

    Int Immunol   Vol. 11 ( 9 ) page: 1491-1500   1999.9

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  168. Gene mutation of transforming growth factor beta1 type II receptor in hepatocellular carcinoma. Reviewed

    Furuta K, Misao S, Takahashi K, Tagaya T, Fukuzawa Y, Ishikawa T, Yoshioka K, Kakumu S.

    Int J Cancer   Vol. 81 ( 6 ) page: 851-853   1999.6

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  169. Polyclonality and multispecificity of the CTL response to a single viral epitope. Reviewed

    Ishikawa T, Kakumu S, Kono D, Chung J, Fowler P, Theofilopoulos A, Chisari FV.

    J Immunol   Vol. 161 ( 11 ) page: 5842-5850   1998.12

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  170. Different constitution of hepatitis C virus population in peripheral blood mononuclear cells and plasma in patients with type C chronic liver disease. Reviewed

    Okumura A, Yoshioka K, Aiyama T, Takayanagi M, Iwata K, Ishikawa T, Kakumu S.

    Dig Dis Sci   Vol. 43 ( 2 ) page: 377-383   1998.2

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  171. Serum levels of IL-10, IL-15 and soluble tumor necrosis factor-alpha (TNF-alpha) receptors in type C chronic liver disease. Reviewed

    Kakumu S, Okumura A, Ishikawa T, Yano M, Enomoto A, Nishimura H, Yoshioka K, Yoshikai Y.

    Clin Exp Immunol   Vol. 109 ( 3 ) page: 458-463   1997.9

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  172. Serial quantitation of serum core protein and viral RNA of hepatitis C virus after interferon therapy: Increase in viral load in biochemical responders. Reviewed

    Yoshioka K, Aiyama T, Iwata K, Yano M, Okumura A, Ishikawa T, Kakumu S.

    Am J Gastroenterol   Vol. 92 ( 8 ) page: 1305-1309   1997.8

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  173. Interleukin 2 and gamma/delta T-cell receptors in peripheral blood of patients with chronic hepatitis C virus infection. Reviewed

    Kakumu S, Ishikawa T, Okumura A, Yoshioka K.

    Hepatol Res   Vol. 7 ( 2 ) page: 83-93   1997.6

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  174. Earlier loss of hepatitis C virus RNA in interferon therapy can predict a long-term response in chronic hepatitis C. Reviewed

    Kakumu S, Aiyama T, Okumura A, Iwata K, Ishikawa T, Yoshioka K.

    J Gastroenterol Hepatol   Vol. 12 ( 6 ) page: 468-472   1997.6

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  175. Production of interleukins 10 and 12 by peripheral blood mononuclear cells (PBMC) in chronic hepatitis C virus (HCV) infection. Reviewed

    Kakumu S, Okumura A, Ishikawa T, Iwata K, Yano M, Yoshioka K.

    Clin Exp Immunol   Vol. 108 ( 1 ) page: 138-143   1997.4

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  176. Humoral immune response to the hypervariable region of hepatitis C virus differs between genotype 1b and 2a. Reviewed

    Yoshioka K, Aiyama T, Okumura A, Takayanagi M, Iwata K, Ishikawa T, Nagai Y, Kakumu S.

    J Infect Dis   Vol. 175 ( 3 ) page: 505-510   1997.3

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  177. Cyclosporine therapy affects amino-transferase activity but not hepatitis C virus RNA levels in chronic hepatitis C. Reviewed

    Kakumu S, Takayanagi M, Iwata K, Okumura A, Aiyama T, Ishikawa T, Nadai M, Yoshioka K.

    J Gastroenterol Hepatol   Vol. 12 ( 1 ) page: 62-66   1997.1

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  178. Hypervariable region sequence in cryoglobulin-associated hepatitis C virus in sera of patients with chronic hepatitis C: relationship to antibody response against hypervariable region genome. Reviewed

    Aiyama T, Yoshioka K, Okumura A, Takayanagi M, Iwata K, Ishikawa T, Kakumu S.

    Hepatology   Vol. 24 ( 6 ) page: 1346-1350   1996.12

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  179. Sequence analysis of hypervariable region of hepatitis C virus (HCV) associated with immune complex in patients with chronic HCV infection. Reviewed

    Aiyama T, Yoshioka K, Okumura A, Takayanagi M, Iwata K, Ishikawa T, Kakumu S.

    J Infect Dis   Vol. 174 ( 6 ) page: 1316-1320   1996.12

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  180. Serial analysis of hepatitis B virus core nucleotide sequence of patients with acute exacerbation during chronic infection. Reviewed

    Okumura A, Takayanagi M, Aiyama T, Iwata K, Wakita T, Ishikawa T, Yoshioka K, Kakumu S.

    J Med Virol   Vol. 49 ( 2 ) page: 103-109   1996.6

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  181. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Reviewed

    Guidotti LG, Ishikawa T, Hobbs MV, Matzke B, Schreiber RD, Chisari FV.

    Immunity   Vol. 4 ( 1 ) page: 25-36   1996.1

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  182. Posttranscriptional clearance of hepatitis B virus RNA by cytotoxic T lymphocyte-activated hepatocytes. Reviewed

    Tsui LV, Guidotti LG, Ishikawa T, Chisari FV.

    Proc Natl Acad Sci USA   Vol. 92 ( 26 ) page: 12398-12402   1995.12

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  183. CTL access to tissue antigen is restricted in vivo. Reviewed

    Ando K, Guidotti LG, Cerny A, Ishikawa T, Chisari FV.

    J Immunol   Vol. 153 ( 2 ) page: 482-488   1994.7

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  184. ClassⅠrestricted cytotoxic T lymphocytes are directly cytopathic for their target cells in vivo. Reviewed

    Ando K, Guidotti LG, Wirth S, Ishikawa T, Missale G, Moriyama T, Schreiber RD, Schricht HJ, Huang S, Chisari FV.

    J Immunol   Vol. 152 ( 7 ) page: 3245-3253   1994.4

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  185. Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. Reviewed

    Guidotti LG, Ando K, Hobbs MV, Ishikawa T, Runkel RD, Schreiber RD, Chisari FV.

    Proc Natl Acad Sci USA   Vol. 91 ( 9 ) page: 3764-3768   1994.4

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  186. Hepatitis C virus genotypes are not responsible for development of serious liver disease. Reviewed

    Yamada M, Kakumu S, Yoshioka K, Higashi Y, Tanaka K, Ishikawa T, Takayanagi M.

    Dig Dis Sci   Vol. 39 ( 2 ) page: 234-239   1994.2

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  187. Interferon-gamma production specific for hepatitis B virus antigen by intrahepatic T lymphocytes in patients with acute and chronic hepatitis B. Reviewed

    Kakumu S, Ishikawa T, Wakita T, Yoshioka K, Takayanagi M, Tahara H, Kusakabe A.

    Am J Gastroenterol   Vol. 89 ( 1 ) page: 92-96   1994.1

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  188. Dynamics of genome change in the E2/NS1 region of hepatitis C virus in vivo. Reviewed

    Higashi Y, Kakumu S, Yoshioka K, Wakita T, Mizokami M, Ohba K, Ito Y, Ishikawa T, Takayanagi M, Nagai Y.

    Virology   Vol. 197 ( 2 ) page: 659-668   1993.12

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  189. Cytotoxic T lymphocyte activity to hepatitis B virus DNA-transfected HepG2 cells in patients with chronic hepatitis B. Reviewed

    Ito Y, Kakumu S, Yoshioka K, Wakita T, Ishikawa T, Koike K.

    J Gastroenterol   Vol. 28 ( 5 ) page: 657-665   1993.10

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  190. Relative immunogenicity of hepatitis B virus-encoded antigens as targets for cytotoxic T cell response. Reviewed

    Ishikawa T, Kakumu S, Yoshioka K, Yamada Y, Tanaka K, Higashi Y, Takayanagi M, Okumura A, Kojima A, Tamura S.

    Immunology   Vol. 80 ( 2 ) page: 313-318   1993.10

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  191. Comparison of envelope and precore/core variants of hepatitis B virus (HBV) during chronic HBV infection. Reviewed

    Takayanagi M, Kakumu S, Wakita T, Ishikawa T, Yoshioka Y, Higashi Y.

    Virology   Vol. 196 ( 1 ) page: 138-145   1993.9

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  192. A pilot study of ribavirin and interferon beta for the treatment of chronic hepatitis C. Reviewed

    Kakumu S, Yoshioka K, Wakita T, Ishikawa T, Takayanagi M, Higashi Y.

    Gastroenterology   Vol. 105 ( 2 ) page: 507-512   1993.8

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  193. Pilot study of ribavirin and interferon-beta for chronic hepatitis B. Reviewed

    Kakumu S, Yoshioka K, Wakita T, Ishikawa T, Takayanagi M, Higashi Y.

    Hepatology   Vol. 18 ( 2 ) page: 258-263   1993.8

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  194. Effects of interferon-alpha treatment on hepatitis B virus antigen-specific immunologic responses in patients with chronic hepatitis B. Reviewed

    Ishikawa T, Kakumu S, Yoshioka K, Kurokawa S, Kusakabe A, Tahara H, Hirofuji H, Kawabe M.

    Liver   Vol. 13 ( 2 ) page: 95-101   1993.4

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  195. Effect of recombinant human transforming growth factor beta1 on immune responses in patients with chronic hepatitis B. Reviewed

    Kakumu S, Ito Y, Takayanagi M, Yoshioka K, Wakita T, Ishikawa T, Higashi Y, Yang ZQ.

    Liver   Vol. 13 ( 2 ) page: 62-68   1993.4

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  196. Effects of transforming growth factor-beta1 against the inhibitory action of interferon on DNA synthesis and viral replication in hepatitis B virus DNA-transfected cells. Reviewed

    Kakumu S, Ito Y, Wakita T, Yoshioka K, Ishikawa T, Tkayanagi M, Higashi Y, Yang ZQ.

    J Med Virol   Vol. 38 ( 1 ) page: 62-66   1992.9

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  197. Detection of hepatitis C virus by polymerase chain reaction and response to interferon-alpha therapy: Relation to genotype of hepatitis C virus. Reviewed

    Yoshioka K, Kakumu S, Wakita T, Ishikawa T, Ito Y, Takayanagi M, Higashi Y, Shibata M, Morishima T.

    Hepatology   Vol. 16 ( 2 ) page: 293-299   1992.8

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  198. Cellular immune response of peripheral blood mononuclear cells to HBV antigens during chronic and acute HBV infection. Reviewed

    Wakita T, Kakumu S, Yoshioka K, Ishikawa T, Ito Y, Shinagawa T.

    Digestion   Vol. 52 ( 1 ) page: 26-33   1992.5

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  199. Immune response of peripheral blood mononuclear cells to antigenic determinants within hepatitis B core antigen in HB virus-infected man. Reviewed

    Ishikawa T, Kakumu S, Yoshioka K, Wakita T, Takayanagi M, Orido E.

    Liver   Vol. 12 ( 2 ) page: 100-105   1992.4

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  200. Interleukin 6 production by peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection and primary biliary cirrhosis. Reviewed

    Kakumu S, Shinagawa T, Ishikawa T, Yoshioka K, Wakita T, Ida N.

    J Gastroenterol   Vol. 28 ( 1 ) page: 18-24   1992.2

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  201. Detection of pre-C and core region mutants of hepatitis B virus (HBV) in chronic HBV carriers. Reviewed

    Wakita T, Kakumu S, Shibata M, Yoshioka K, Ito Y, Shinagawa T, Ishikawa T, Takayanagi M, Morishima T.

    J Clin Invest   Vol. 88 ( 6 ) page: 1793-1801   1991.12

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  202. Serum interleukin 6 levels in patients with chronic hepatitis B. Reviewed

    Kakumu S, Shinagawa T, Ishikawa T, Yoshioka K, Wakita T, Ito Y, Takayanagi M, Ida N.

    Am J Gastroenterol   Vol. 86 ( 12 ) page: 1804-1808   1991.12

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  203. Apoptosis in cultured rat hepatocytes: The effects of tumor necrosis factor alpha and interferon gamma. Reviewed

    Shinagawa T, Yoshioka K, Kakumu S, Wakita T, Ishikawa T, Ito Y, Takayanagi M.

    J Pathol   Vol. 165 ( 3 ) page: 247-253   1991.11

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  204. Anti-hepatitis C antibodies in patients with chronic non-A, non-B hepatitis: relation to disease progression and effect of interferon alpha. Reviewed

    Yoshioka K, Kakumu S, Hayashi H, Shinagawa T, Wakita T, Ishikawa T, Ito Y, Takayanagi M.

    Am J Gastroenterol   Vol. 86 ( 10 ) page: 1495-1499   1991.10

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  205. Treatment with human gamma interferon of chronic hepatitis B: Comparative study with alpha interferon. Reviewed

    Kakumu S, Ishikawa T, Mizokami M, Orido E, Yoshioka K, Wakita T, Yamamoto M.

    J Med Virol   Vol. 35 ( 1 ) page: 32-37   1991.9

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  206. Effect of sizofiran, a polysaccharide, on interferon gamma, antibody and lymphocyte proliferation specific for hepatitis B virus antigen in patients with chronic hepatitis B. Reviewed

    Kakumu S, Ishikawa T, Wakita T, Yoshioka K, Ito Y, Shinagawa T.

    Int J Immunopharm   Vol. 13 ( 7 ) page: 969-976   1991.7

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  207. In vitro production of anti-mitochondrial antibody by peripheral blood mononuclear cells in patients with primary biliary cirrhosis. Reviewed

    Ishikawa T, Kakumu S, Wakita T, Takayanagi M, Yoshioka K.

    J Clin Lab Immunol   Vol. 35 ( 1 ) page: 17-25   1991.5

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  208. T cell lines reactive with hepatitis B core and e antigens in patients with chronic hepatitis B. Reviewed

    Ishikawa T, Kakumu S, Yoshioka K, Wakita T, Shinagawa T, Ito Y.

    J Clin Lab Immunol   Vol. 34 ( 4 ) page: 151-156   1991.4

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  209. Effects of TJ-9 Sho-saiko-to (Kampo Medicine) on interferon gamma and antibody production specific for hepatitis B virus antigen in patients with type B chronic hepatitis. Reviewed

    Kakumu S, Yoshioka K, Wakita T, Ishikawa T.

    Int J Immunopharm   Vol. 13 ( 2/3 ) page: 141-146   1991.2

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  210. Comparison of peripheral blood and hepatic lymphocyte subpopulations and interferon production in chronic viral hepatitis. Reviewed

    Kakumu S, Yoshioka K, Wakita T, Ishikawa T, Murase A, Kusakabe A, Kurokawa S.

    J Clin Lab Immunol   Vol. 33 ( 1 )   1990.9

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  211. Immunohistochemical studies of intrahepatic tumor necrosis factor alpha in chronic liver disease. Reviewed

    Yoshioka K, Kakumu S, Arao M, Tsutsumi Y, Inoue M, Wakita T, Ishikawa T, Mizokami M.

    J Clin Pathol   Vol. 43 ( 4 ) page: 298-302   1990.4

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  212. In vitro production of antibody to hepatitis B core and e antigen by prepheral blood mononuclear cells in patients with chronic hepatitis B virus infection. Reviewed

    Tsutsumi Y, Kakumu S, Wakita T, Yoshioka K, Ishikawa T.

    J Immunol   Vol. 144 ( 6 ) page: 2389-2393   1990.3

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▼display all

Books 46

  1. 必ず役立つ! 肝炎診療バイブル

    三田英治、平松直樹 他( Role: Contributor ,  アルコール性肝障害の診断と治療)

    メディカ出版  2021.7  ( ISBN:978-4840475679

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    Total pages:384   Responsible for pages:196 - 205   Language:Japanese Book type:Textbook, survey, introduction

  2. B型肝炎ワクチンとアジュバント 「次世代アジュバント開発のためのメカニズム解明と安全性」

    伊藤弘康、石川哲也

    シーエムシー出版  2017 

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    Responsible for pages:309-315   Language:Japanese

  3. 血液検査:免疫学的検査、一般検査 「ここまできた肝臓病診療」

    石川哲也( Role: Contributor)

    中山書店  2017 

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    Responsible for pages:114-120   Language:Japanese

  4. ウイルス肝炎の発症機序肝臓専門医テキスト 改訂第2版(日本肝臓学会編)

    石川哲也( Role: Contributor)

    南江堂  2016 

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    Responsible for pages:36-39   Language:Japanese

  5. C型肝炎治療の現状について

    石川哲也( Role: Contributor)

    明日の臨床  2015 

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    Responsible for pages:29 - 34   Language:Japanese

  6. B型肝炎 病態 B型肝炎の発症機序と病態

    石川哲也( Role: Contributor)

    日本臨床  2015 

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    Responsible for pages:429 - 433   Language:Japanese

  7. ウイルス肝炎の発症機序 「肝臓専門医テキスト 日本肝臓学会編」

    石川哲也( Role: Sole author)

    南江堂  2013.3  ( ISBN:978-4-524-26812-2

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    Language:Japanese

  8. B型肝炎についての最近の話題

    石川哲也( Role: Sole author)

    健康文化振興財団  2012.10 

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    Language:Japanese

  9. B型慢性肝炎 「肝疾患レジデントマニュアル」

    石川哲也( Role: Sole author)

    医学書院  2008.10 

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    Language:Japanese

  10. 画像検査所見、病理検査所見 「重篤副作用疾患別対応マニュアル 第2集」

    石川哲也( Role: Sole author)

    日本医薬情報センター  2008.7 

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    Language:Japanese

  11. 肝疾患レジデントマニュアル

    柴田 実, 八橋 弘, 石川 哲也, 伊東 和樹( Role: Joint author)

    医学書院  2008  ( ISBN:9784260006408

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  12. C型急性肝炎 「消化器疾患最新の治療2007-2008」

    石川哲也( Role: Sole author)

    南江堂  2007.3 

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    Language:Japanese

  13. HCVキャリアの指導、管理および院内感染事故対策 「今日の治療指針 2007年度版」

    石川哲也( Role: Sole author)

    医学書院  2007.1 

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    Language:Japanese

  14. B型肝炎 -急性肝炎- 「肝臓病学」

    各務伸一,石川哲也( Role: Joint author)

    朝倉書店  2006.8 

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    Language:Japanese

  15. 慢性肝炎 「ガイドライン外来診療2006」

    石川哲也( Role: Sole author)

    日経メディカル開発  2006.3 

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    Language:Japanese

  16. HBVキャリアの指導、管理および院内感染事故対策 「今日の治療指針 2006年度版」

    石川哲也( Role: Sole author)

    医学書院  2006.1 

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    Language:Japanese

  17. 概説-肝疾患- 「中高年・疾病予防(健康づくり)のための運動の実際」

    石川哲也( Role: Sole author)

    全日本病院出版会  2005.10 

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  18. 急性ウイルス肝炎:B型肝炎 「臨床消化器病学」

    各務伸一,石川哲也( Role: Joint author)

    朝倉書店  2005.9 

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  19. 慢性ウイルス肝炎:B型肝炎 「臨床消化器病学」

    各務伸一,石川哲也( Role: Joint author)

    朝倉書店  2005.9 

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  20. B型肝炎 「肝疾患と免疫」

    石川哲也( Role: Sole author)

    医薬ジャーナル社  2005.3 

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  21. B型肝炎の発症機序とHBV持続感染 「ウイルス性肝炎 消化器3」

    石川哲也,各務伸一( Role: Joint author)

    最新医学社  2005.2 

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  22. B型肝炎:ウイルス、病態、診断 「Annual Review 消化器2005」

    各務伸一,奥村明彦,石川哲也( Role: Joint author)

    中外医薬社  2005.1 

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  23. ラミブジンとHBワクチン併用療法の効果と問題点 「ウイルス性肝炎 下- 基礎・臨床研究の進歩-」

    石川哲也,各務伸一( Role: Joint author)

    日本臨床社  2004.8 

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  24. B型慢性肝炎 「消化器病診療 -良きインフォームド・コンセントに向けて-」

    各務伸一,石川哲也,奥村明彦( Role: Joint author)

    医学書院  2004.5 

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  25. B型肝炎 免疫療法 「コンセンサス 肝疾患 治療 2004」

    石川哲也( Role: Sole author)

    アークメディア  2003.12 

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  26. 慢性肝炎,肝硬変の治療;ワクチン治療 「消化器病セミナー91 -ウイルス肝炎の治療はどのように変わったか-」

    石川哲也,各務伸一( Role: Joint author)

    へるす出版  2003.6 

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  27. 肝細胞のケモカイン産生が炎症の方向性に与える影響について 「再生・増殖・分化と消化器病」

    田邊純一,石川哲也,奥村明彦,前野禎,佐藤顕,綾田穣,堀田直樹,多賀谷恒明,福沢義孝,吉岡健太郎.各務伸( Role: Joint author)

    アークメディア  2002.10 

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  28. B型慢性肝炎におけるラミブジンとワクチンの併用療法 「B型・C型肝炎治療の新しい展開」

    各務伸一,石川哲也( Role: Joint author)

    犬山シンポジウム記録刊行会、アークメディア  2002.10 

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  29. B型肝炎 病態 「コンセンサス肝疾患2002 診断・治療と病態」

    石川哲也( Role: Sole author)

    日本メディカルセンター  2002.3 

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  30. 肝と免疫 「Annual Review 消化器2002」

    各務伸一,奥村明彦,石川哲也( Role: Joint author)

    中外医薬社  2002.1 

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  31. The mechanism of liver injury in hepatitis B virus infection. “Molecular Biology and Immunology in Hepatology-Advances in the Treatment of Intractable Liver Diseases-“

    Ishikawa T, Kakumu S.( Role: Joint author)

    Elsevier Science B.V.  2002 

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  32. B型肝炎の免疫学的治療の検討-HBVトランスジェニックマウスを用いて- 「肝臓フォーラム '01記録集」

    石川哲也( Role: Sole author)

    2002 

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  33. B型慢性肝炎に対するワクチン+ラミブジン併用療法 「B型肝炎の新しい展開」

    各務伸一,石川哲也( Role: Joint author)

    犬山シンポジウム記録刊行会、アークメディア  2001.10 

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  34. ウイルス肝炎:B型 「消化器疾患の分子医学」

    石川哲也,各務伸一( Role: Joint author)

    日本メディカルセンター  2001.5 

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  35. B型肝炎とは 「慢性肝疾患診療マニュアル」

    石川哲也,各務伸一( Role: Joint author)

    2001.5 

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  36. 肝細胞のケモカイン産生に対するサイトカインの影響 「肝の生化学」

    石川哲也,田邊純一,各務伸一( Role: Joint author)

    箱根シンポジウム記録刊行会  2000.7 

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  37. The mechanism of liver injury and viral clearance in hepatitis B virus infection. “Progress in Hepatology”

    Ishikawa T, Kakumu S( Role: Joint author)

    Elsevier Science B.V.  1999.12 

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  38. ウイルス抗原に対する免疫応答の多様性と変異によるウイルス逃避の可能性について 「消化器疾患と細胞内情報伝達」

    石川哲也( Role: Sole author)

    アークメディア  1999.10 

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  39. B型肝炎 「医学のあゆみ 消化器疾患 Ver.2 II. 肝・胆・膵」

    石川哲也,各務伸一( Role: Joint author)

    1999.6 

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  40. 肝炎慢性化におけるcostimulatory moleculeの関与 -CD8+細胞障害性Tリンパ球(CTL)の機能に与える影響について- 「肝免疫の最前線」

    石川哲也,景山正之,奥村明彦,各務伸一( Role: Joint author)

    マイライフ社  1999 

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  41. 発症機序と診断(B型肝炎) 「肝臓病 今日の診断と最新の治療」

    各務伸一,石川哲也( Role: Joint author)

    国際医書出版  1997.12 

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  42. Role of immune response on liver cell injury and regulation of the virus.“Frontier in Hepatology '97”

    Ishikawa T, Chisari FV, Kakumu S.( Role: Joint author)

    Axel Springer Japan Publishing Inc.  1997.7 

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  43. マウスHBs抗原特異的CTLのレパトア解析とその意義 「肝臓病学の最前線 1997」

    各務伸一,石川哲也( Role: Joint author)

    中外医薬社  1997.7 

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  44. ウイルソン病 「肝臓病の原因と治療」

    石川哲也( Role: Sole author)

    PHP研究所  1997.3 

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  45. B型肝炎 -肝細胞障害のメカニズム-「消化器診療プラクティス 14 自己免疫性肝炎」

    石川哲也,各務伸一( Role: Joint author)

    文光堂  1996.8 

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  46. B型肝炎 「肝と免疫」

    石川哲也( Role: Sole author)

    医薬ジャーナル社  1996.8 

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▼display all

MISC 70

  1. 肝細胞キメラマウス作製系における移植肝細胞の生着、拒絶の動態と拒絶回避のための治療について

    玉置 優貴, 堀 純子, 名仁澤 英里, 林 由美, 石川 哲也

    臨床病理   Vol. 68 ( 補冊 ) page: 193 - 193   2020.10

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    Language:Japanese   Publisher:(一社)日本臨床検査医学会  

  2. 非肝癌症例と肝発癌症例の違いに関与する腸内細菌の検討

    本多 隆, 石上 雅敏, 山本 崇文, 犬飼 庸介, 杉山 由晃, 吉岡 直輝, 水野 和幸, 武藤 久哲, 横山 晋也, 田中 卓, 山本 健太, 伊藤 隆徳, 石津 洋二, 葛谷 貞二, 石川 哲也, 藤城 光弘

    肝臓   Vol. 61 ( Suppl.2 ) page: A701 - A701   2020.9

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  3. 腫瘍肝占拠率50%以上の高度進行肝細胞癌に対する分子標的治療薬の治療効果の検討~ソラフェニブとレンバチニブの比較~

    武藤久哲, 葛谷貞二, 杉山由晃, 吉岡直輝, 水野和幸, 横山晋也, 田中卓, 山本健太, 伊藤隆徳, 石津洋二, 本多隆, 石川哲也, 石上雅敏, 藤城光弘

    肝臓   Vol. 61 ( Supplement 1 ) page: A371 - A371   2020

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    J-GLOBAL

  4. 肝細胞キメラマウス作製系を用いたアロ肝細胞に対する免疫拒絶反応の解析

    玉置優貴, 名仁澤英里, 宮下凛太朗, 園玲華, 林由美, 石川哲也

    臨床病理   Vol. 67 ( 補冊 ) page: 166 - 166   2019

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    J-GLOBAL

  5. B型肝炎ウイルスの生活環におけるエンドサイトーシス経路の役割

    宮下凜太郎, 名仁澤英里, 園玲華, 玉置優貴, 林由美, 石川哲也

    臨床病理   Vol. 67 ( 補冊 ) page: 257 - 257   2019

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    J-GLOBAL

  6. B型肝炎ウイルストランスジェニックマウスにおける肝細胞の小胞体ストレスと肝障害重症化機序

    園玲華, 石川哲也, 林由美, 名仁澤英里, 玉置優貴, 宮下凛太郎

    臨床病理   Vol. 67 ( 補冊 ) page: 258 - 258   2019

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    J-GLOBAL

  7. 新規HBV感染マウスモデル作製と宿主免疫応答の解析

    神戸歩, 伊藤弘康, 石川哲也

    肝臓   Vol. 60 ( Supplement 1 )   2019

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  8. マウス肝障害モデルにおけるトロンボモジュリン遺伝子導入脂肪由来幹細胞の炎症軽減効果について

    山本 万智, 名仁澤 英里, 今井田 藍, 山崎 花那子, 園 玲華, 玉置 優貴, 宮下 凛太郎, 林 由美, 石川 哲也

    臨床病理   Vol. 66 ( 補冊 ) page: 233 - 233   2018.10

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  9. B型肝炎ウイルス粒子の蛍光ラベルによる可視化と細胞内取込み機構の解析

    山崎 花那子, 今井田 藍, 名仁澤 英里, 山本 万智, 宮下 凛太郎, 玉置 優貴, 園 玲華, 林 由美, 石川 哲也

    臨床病理   Vol. 66 ( 補冊 ) page: 251 - 251   2018.10

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  10. B型肝炎ウイルス粒子可視化技術を用いたウイルス生活環の解析

    今井田 藍, 山崎 花那子, 山本 万智, 名仁澤 英里, 玉置 優貴, 宮下 凛太郎, 園 玲華, 林 由美, 石川 哲也

    臨床病理   Vol. 66 ( 補冊 ) page: 251 - 251   2018.10

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  11. 量子ドットを用いた移植幹細胞・免疫細胞間interaction蛍光イメージング

    北村 晃大, 湯川 博, 佐藤 和秀, 有本 知子, 小野島 大介, 石川 哲也, 馬場 嘉信

    バイオイメージング   Vol. 27 ( 2 ) page: 83 - 83   2018.8

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  12. 探針エレクトロスプレーイオン化タンデム質量分析(PESI/MS/MS)を用いたin vivoリアルタイム・モニタリングシステムの構築

    林 由美, 財津 桂, 村田 匡, 土橋 均, 石井 晃, 緒方 是嗣, 石川 哲也

    JSBMS Letters   Vol. 43 ( Suppl. ) page: 144 - 144   2018.8

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  13. 量子ドットによる移植幹細胞・免疫細胞間インターラクションin vivo蛍光イメージング

    北村 晃大, 湯川 博, 佐藤 和秀, 有本 知子, 小野島 大介, 石川 哲也, 馬場 嘉信

    日本DDS学会学術集会プログラム予稿集   Vol. 34回 ( 2 ) page: 156 - 156   2018.5

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  14. 進行肝細胞癌に対するソラフェニブ投与後の肝予備能推移 初回画像PD判定時にレゴラフェニブへの切り替え条件を満たすかにも着目して

    葛谷 貞二, 石上 雅敏, 武藤 久哲, 横山 晋也, 田中 卓, 山本 健太, 安藤 祐資, 伊藤 隆徳, 安田 諭, 石津 洋二, 本多 隆, 林 和彦, 石川 哲也, 廣岡 芳樹, 後藤 秀実

    日本消化器病学会雑誌   Vol. 115 ( 臨増総会 ) page: A283 - A283   2018.3

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  15. 肝硬変患者におけるサルコペニアと栄養状態・QOLとの関連性

    安藤 祐資, 石上 雅敏, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石川 哲也, 廣岡 芳樹, 後藤 秀実

    日本消化器病学会雑誌   Vol. 115 ( 臨増総会 ) page: A297 - A297   2018.3

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  16. C型慢性肝炎・肝硬変患者に対するDAAs治療が血球数に与える影響

    石津 洋二, 石上 雅敏, 武藤 久哲, 横山 晋也, 田中 卓, 山本 健太, 安藤 祐資, 伊藤 隆徳, 安田 諭, 葛谷 貞二, 本多 隆, 林 和彦, 廣岡 芳樹, 石川 哲也, 後藤 秀実

    日本消化器病学会雑誌   Vol. 115 ( 臨増総会 ) page: A313 - A313   2018.3

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  17. 進行肝細胞癌に対するレゴラフェニブの投与後早期(6週間以内)の治療成績-ソラフェニブ導入時との比較-

    葛谷貞二, 石上雅敏, 武藤久哲, 横山晋也, 田中卓, 山本健太, 安藤祐資, 伊藤隆徳, 安田諭, 石津洋二, 本多隆, 林和彦, 石川哲也, 廣岡芳樹, 後藤秀実

    肝臓   Vol. 59 ( Supplement 1 ) page: A509 - A509   2018

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    J-GLOBAL

  18. 探針エレクトロスプレーイオン化タンデム質量分析(PESI/MS/MS)とScheduled SRM法を用いた生体組織のインタクト・メタボロミクス法の構築

    近藤健太, 林由美, 林由美, 村田匡, 土屋弥月, 大原倫美, 石川哲也, 緒方是嗣, 土橋均, 石井晃, 財津桂, 財津桂

    JSBMS Letters   Vol. 43 ( Supplement ) page: 143 - 143   2018

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    J-GLOBAL

  19. 3年半ぶりのソラフェニブ増量にて完全奏功が得られた進行肝細胞癌の1例

    武藤久哲, 葛谷貞二, 横山晋也, 田中卓, 山本健太, 安藤祐資, 伊藤隆徳, 安田諭, 石津洋二, 本多隆, 林和彦, 石上雅敏, 石川哲也, 廣岡芳樹, 後藤秀実

    Liver Cancer Journal   ( Suppl.1 ) page: 52 - 53   2018

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    J-GLOBAL

  20. 量子ドットイメージング技術を用いた移植幹細胞に対する細胞間interaction機構解明(一般研究発表用)

    北村晃大, 湯川博, 湯川博, 佐藤和秀, 有本知子, 小野島大介, 小野島大介, 石川哲也, 馬場嘉信, 馬場嘉信, 馬場嘉信, 馬場嘉信

    中部化学関係学協会支部連合秋季大会講演予稿集   Vol. 49th   2018

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  21. 分子動力学法を用いたpregenome RNAを内包したB型肝炎ウイルスの物性解明

    山口陽平, 今井甫, 藤本和士, 浦野諒, 篠田渉, 尾曲克己, 田中靖人, 石川哲也, 中川敦史, 岡崎進

    分子シミュレーション討論会講演要旨集   Vol. 32nd   2018

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  22. 量子ドットイメージング技術を用いた移植幹細胞と免疫細胞のinteraction機構解明

    北村晃大, 湯川博, 佐藤和秀, 有本知子, 小野島大介, 小野島大介, 石川哲也, 馬場嘉信, 馬場嘉信, 馬場嘉信, 馬場嘉信

    日本再生医療学会総会(Web)   Vol. 17th   2018

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  23. 量子ドットによる移植幹細胞・免疫細胞間インターラクションin vivo蛍光イメージング

    北村晃大, 湯川博, 佐藤和秀, 有本知子, 小野島大介, 小野島大介, 石川哲也, 馬場嘉信, 馬場嘉信, 馬場嘉信, 馬場嘉信

    日本化学会春季年会講演予稿集(CD-ROM)   Vol. 98th   2018

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  24. 進行肝細胞癌に対するソラフェニブ投与後の肝予備能推移-初回画像PD判定時にレゴラフェニブへの切り替え条件を満たすかにも着目して-

    葛谷貞二, 石上雅敏, 武藤久哲, 横山晋也, 田中卓, 山本健太, 安藤祐資, 伊藤隆徳, 安田諭, 石津洋二, 本多隆, 林和彦, 石川哲也, 廣岡芳樹, 後藤秀実

    日本消化器病学会雑誌(Web)   Vol. 115   2018

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  25. 肝硬変患者におけるサルコペニアと栄養状態・QOLとの関連性

    安藤祐資, 石上雅敏, 石津洋二, 葛谷貞二, 本多隆, 林和彦, 石川哲也, 廣岡芳樹, 後藤秀実

    日本消化器病学会雑誌(Web)   Vol. 115   2018

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  26. 探針エレクトロスプレータンデム質量分析(PESI/MS/MS)を用いた簡便かつ超迅速な血中シアン化物スクリーニング法の構築

    久恒一晃, 久恒一晃, 林由美, 林由美, 村田匡, 大原倫美, 肥田宗政, 土橋均, 石川哲也, 石井晃, 緒方是嗣, 財津桂, 財津桂

    日本法科学技術学会誌   Vol. 23 ( Supplement )   2018

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  27. 量子ドットによる増殖癌細胞・免疫細胞in vivo蛍光イメージング技術の構築

    北村 晃大, 湯川 博, 佐藤 和秀, 有本 知子, 小野島 大介, 石川 哲也, 馬場 嘉信

    Organ Biology   Vol. 24 ( 3 ) page: 93 - 93   2017.11

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  28. 線維化進展例におけるIFNフリー抗HCV治療の効果 IFN時代と比較して何が変わったか?

    石上 雅敏, 安藤 祐資, 林 和彦, 本多 隆, 葛谷 貞二, 石津 洋二, 伊藤 隆徳, 安田 諭, 山本 健太, 田中 卓, 横山 晋也, 中野 功, 石川 哲也, 後藤 秀実

    肝臓   Vol. 58 ( Suppl.2 ) page: A628 - A628   2017.9

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  29. 好酸球増多症を合併したBudd Chiari症候群の1例

    石津 洋二, 石上 雅敏, 横山 晋也, 田中 卓, 安藤 祐資, 伊藤 隆徳, 安田 諭, 野村 彩, 葛谷 貞二, 本多 隆, 林 和彦, 廣岡 芳樹, 石川 哲也, 後藤 秀実

    日本門脈圧亢進症学会雑誌   Vol. 23 ( 3 ) page: 135 - 135   2017.8

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  30. 量子・磁気ナノハイブリッド粒子による幹細胞イメージングおよびハイパーサーミア効果

    小林 香央里, 湯川 博, 村田 勇樹, 城 潤一郎, 小野島 大介, 山本 雅哉, 石川 哲也, 田畑 泰彦, 馬場 嘉信

    日本DDS学会学術集会プログラム予稿集   Vol. 33回   page: 235 - 235   2017.6

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  31. セロトニン症候群モデルラットにおける筋肉の異常収縮と血漿メタボローム・プロファイルの関連性

    財津 桂, 野田 沙樹, 林 由美, 大原 倫美, 井口 亮, 草野 麻衣子, 佐藤 貴子, 土橋 均, 石川 哲也, 鈴木 廣一, 石井 晃

    The Journal of Toxicological Sciences   Vol. 42 ( Suppl. ) page: S197 - S197   2017.6

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  32. 細胞トレーシングのためのDDS 量子ドットによる移植幹細胞in vivo蛍光イメージング

    湯川 博, 石川 哲也, 田畑 泰彦, 馬場 嘉信

    日本DDS学会学術集会プログラム予稿集   Vol. 33回   page: 90 - 90   2017.6

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  33. 門脈腫瘍栓を伴う進行肝細胞癌に対するソラフェニブの治療成績 6週PD判定の有無に着目して

    葛谷 貞二, 石上 雅敏, 横山 晋也, 田中 卓, 山本 健太, 安藤 祐資, 伊藤 隆徳, 安田 諭, 野村 彩, 石津 洋二, 本多 隆, 林 和彦, 石川 哲也, 廣岡 芳樹, 後藤 秀実

    肝臓   Vol. 58 ( Suppl.1 ) page: A275 - A275   2017.4

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  34. 慢性肝疾患患者における生活習慣による腸内細菌への影響

    山本 健太, 石上 雅敏, 田中 卓, 安藤 祐資, 伊藤 隆徳, 安田 諭, 野村 彩, 加藤 幸一郎, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 廣岡 芳樹, 石川 哲也, 後藤 秀実

    肝臓   Vol. 58 ( Suppl.1 ) page: A237 - A237   2017.4

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  35. 歯髄幹細胞無血清培養上清による難治性肝疾患での有用性の検討 急性・慢性肝炎動物モデルにおける効果発現メカニズムの違いに着目して

    伊藤 隆徳, 田中 卓, 山本 健太, 安藤 祐資, 安田 諭, 野村 彩, 加藤 幸一郎, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石上 雅敏, 廣岡 芳樹, 石川 哲也, 後藤 秀実

    肝臓   Vol. 58 ( Suppl.1 ) page: A256 - A256   2017.4

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  36. C型慢性肝炎における線維化進展例(Fib4 index≧3.25)におけるウイルス消失後の肝予備能の変化

    石上 雅敏, 林 和彦, 本多 隆, 葛谷 貞二, 石津 洋二, 野村 彩, 伊藤 隆徳, 安田 諭, 安藤 祐資, 山本 健太, 田中 卓, 横山 晋也, 石川 哲也, 中野 功, 廣岡 芳樹, 後藤 秀実

    肝臓   Vol. 58 ( Suppl.1 ) page: A311 - A311   2017.4

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  37. メタボロミクスによる妊娠期DEHP曝露における胎児低生存率の解析

    林 由美, 財津 桂, 名仁澤 英里, 平野 文香, 大原 倫美, 野田 沙樹, 石井 晃, 伊藤 由起, 那須 民江, 石川 哲也

    日本衛生学雑誌   Vol. 72 ( Suppl. ) page: S198 - S198   2017.3

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  38. BIOINDUSTRY・NIR-II近赤外領域における移植幹細胞in vivo蛍光イメージング

    BIOINDUSTRY・NIR-II近赤外領域における移植幹細胞in vivo蛍光イメージング   Vol. 34 ( 1 ) page: 27 - 34   2017.1

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  39. DDS・イメージング 量子ドットによる移植幹細胞in vivo蛍光イメージング手法の構築

    湯川 博, 石川 哲也, 馬場 嘉信

    日本バイオマテリアル学会大会予稿集   Vol. シンポジウム2016   page: 215 - 215   2016.11

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  40. 再生医療 いま見えてきた課題 量子ドットによる移植幹細胞in vivo蛍光リアルタイムイメージング

    湯川 博, 有本 知子, 吉住 寧真, 荻原 裕佑, 石川 哲也, 馬場 嘉信

    Organ Biology   Vol. 23 ( 3 ) page: 60 - 60   2016.10

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  41. 肝臓特異的UBXD8ノックアウトは脂質負荷・コリン欠乏に対し線維化形成を促進する

    今井 則博, 山本 健太, 安藤 祐資, 伊藤 隆徳, 安田 諭, 野村 彩, 加藤 幸一郎, 新家 卓郎, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石上 雅敏, 廣岡 芳樹, 石川 哲也, 後藤 秀実

    肝臓   Vol. 57 ( Suppl.2 ) page: A553 - A553   2016.9

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  42. 新規M2マクロファージ誘導因子を用いた難治性肝疾患治療法の開発

    伊藤 隆徳, 山本 朗仁, 山本 健太, 安藤 祐資, 安田 諭, 野村 彩, 加藤 幸一郎, 新家 卓郎, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石上 雅敏, 廣岡 芳樹, 石川 哲也, 日比 英晴, 後藤 秀実

    肝臓   Vol. 57 ( Suppl.2 ) page: A550 - A550   2016.9

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  43. 肝硬変患者におけるpresarcopeniaが推算糸球体濾過量(eGFR)に与える影響

    石津 洋二, 石上 雅敏, 山本 健太, 安藤 祐資, 伊藤 隆徳, 安田 諭, 野村 彩, 加藤 幸一郎, 新家 卓郎, 葛谷 貞二, 本多 隆, 林 和彦, 廣岡 芳樹, 石川 哲也, 後藤 秀実

    肝臓   Vol. 57 ( Suppl.2 ) page: A607 - A607   2016.9

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  44. B型慢性肝炎におけるインターフェロン治療によるCoreI97の変化と肝炎沈静化

    本多 隆, 石上 雅敏, 山本 健太, 安藤 佑資, 安田 諭, 伊藤 隆徳, 野村 彩, 加藤 幸一郎, 新家 卓郎, 石津 洋二, 葛谷 貞二, 林 和彦, 廣岡 芳樹, 石川 哲也, 中野 功, 後藤 秀実

    肝臓   Vol. 57 ( Suppl.2 ) page: A530 - A530   2016.9

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  45. 脂質メディエーターとメタボローム解析によるPPARαノックアウトマウスを用いたコカイン誘発性肝障害の解析

    篠田 諭, 林 由美, 財津 桂, 酒井 佑一朗, 山中 麻友美, 那須 民江, 石川 哲也, 吉本 高士, 草野 麻衣子, 土橋 均, 石井 晃

    The Journal of Toxicological Sciences   Vol. 41 ( Suppl. ) page: S258 - S258   2016.6

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  46. ダクラタスビル+アスナプレビル治療症例におけるHCV抗原特異的免疫応答の変化について

    加藤 幸一郎, 石川 哲也, 石津 洋二, 荒川 恭宏, 安藤 祐資, 伊藤 隆徳, 安田 諭, 川口 彩, 新家 卓郎, 今井 則博, 葛谷 貞二, 本多 隆, 林 和彦, 石上 雅敏, 後藤 秀実

    肝臓   Vol. 57 ( Suppl.1 ) page: A324 - A324   2016.4

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  47. B型肝炎研究のUp-To-Date B型肝炎ウイルス粒子可視化による細胞内侵入機構の解析

    石川 哲也, 湯川 博

    肝臓   Vol. 57 ( Suppl.1 ) page: A25 - A25   2016.4

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  48. 肝細胞癌合併血友病患者に対するラジオ波焼灼術の安全性についての検討

    石津 洋二, 石上 雅敏, 安藤 祐資, 伊藤 隆徳, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 葛谷 貞二, 本多 隆, 林 和彦, 廣岡 芳樹, 石川 哲也, 後藤 秀実

    日本消化器病学会雑誌   Vol. 113 ( 臨増総会 ) page: A272 - A272   2016.3

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  49. HBs抗原消失がみられI97L変異の長期観察ができた症例の検討

    本多 隆, 石上 雅敏, 安藤 祐資, 安田 諭, 伊藤 隆徳, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 石津 洋二, 葛谷 貞二, 林 和彦, 中野 功, 石川 哲也, 後藤 秀実

    日本消化器病学会雑誌   Vol. 113 ( 臨増総会 ) page: A392 - A392   2016.3

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  50. 【新ウイルス性肝炎学-最新の基礎・臨床研究情報-】B型肝炎 病態 B型肝炎の発症機序と病態

    石川 哲也

    日本臨床   Vol. 73 ( 増刊9 新ウイルス性肝炎学 ) page: 429 - 433   2015.12

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  51. 高齢者C型慢性肝炎におけるDaclatasvir/Asunaprevir併用療法の早期反応と治療効果

    本多 隆, 石上 雅敏, 安藤 祐資, 安田 諭, 伊藤 隆徳, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 石津 洋二, 葛谷 貞二, 林 和彦, 石川 哲也, 中野 功, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.3 ) page: A1046 - A1046   2015.11

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  52. ダクラタスビル+アスナプレビル治療中のHCV抗原特異的免疫応答の変化について

    加藤 幸一郎, 荒川 恭宏, 石川 哲也, 安藤 祐資, 伊藤 隆徳, 安田 諭, 川口 彩, 新家 卓郎, 今井 則博, 阿知波 宏一, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石上 雅敏, 脇田 隆字, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.3 ) page: A995 - A995   2015.11

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  53. バルーン閉塞下逆行性経静脈的塞栓術後の肝予備能の変化と肝臓体積の関連性

    石津 祥二, 石上 雅敏, 安藤 祐資, 伊藤 隆徳, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 葛谷 貞二, 本多 隆, 林 和彦, 廣岡 芳樹, 石川 哲也, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.3 ) page: A1031 - A1031   2015.11

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  54. 超低毒性量子ドットによる幹細胞標識及び3D in vivoイメージング

    荻原 裕佑, 湯川 博, 小野島 大介, 亀山 達也, 林 由美, 鳥本 司, 石川 哲也, 馬場 嘉信

    日本バイオマテリアル学会大会予稿集   Vol. 37回   page: 338 - 338   2015.11

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  55. CA19-9高値で見つかった進行肝細胞癌に対しソラフェニブが奏功した一例

    安田 諭, 葛谷 貞二, 安藤 祐資, 伊藤 隆徳, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 石津 洋二, 本多 隆, 林 和彦, 石上 雅敏, 廣岡 芳樹, 石川 哲也, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.3 ) page: A1051 - A1051   2015.11

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  56. M2マクロファージ誘導因子を用いた肝細胞保護効果の検討

    伊藤 隆徳, 松下 嘉泰, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石上 雅敏, 廣岡 芳樹, 石川 哲也, 山本 朗仁, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.3 ) page: A930 - A930   2015.11

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  57. 脂肪由来幹細胞が細胞傷害性Tリンパ球機能に与える影響について

    中切 健太, 大原 倫美, 平野 文香, 名仁澤 英里, 林 由美, 石川 哲也

    臨床病理   Vol. 63 ( 補冊 ) page: 216 - 216   2015.10

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  58. レプチンが脂肪由来幹細胞の分化能に与える影響について

    大原 倫美, 中切 健太, 名仁澤 英里, 平野 文香, 林 由美, 石川 哲也

    臨床病理   Vol. 63 ( 補冊 ) page: 215 - 215   2015.10

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  59. 進行肝細胞癌に対するソラフェニブ投与後早期のPIVKA-2値の推移と抗腫瘍効果との関係

    葛谷 貞二, 石上 雅敏, 伊藤 隆徳, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 石津 洋二, 本多 隆, 林 和彦, 石川 哲也, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.2 ) page: A748 - A748   2015.9

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  60. バイポーラ電極針を用いたラジオ波焼灼術におけるDexmedetomidineを用いた鎮静法の検討

    石津 洋二, 石上 雅敏, 伊藤 隆徳, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 葛谷 貞二, 本多 隆, 林 和彦, 石川 哲也, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.2 ) page: A740 - A740   2015.9

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  61. 肝再生 基礎から臨床 マウス急性肝障害モデルにおける移植後脂肪由来幹細胞の生体内動態解析

    石川 哲也, 吉住 寧真, 湯川 博

    肝臓   Vol. 56 ( Suppl.2 ) page: A653 - A653   2015.9

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    Language:Japanese   Publisher:(一社)日本肝臓学会  

  62. 進行肝細胞癌に対するソラフェニブ不応後TACEを組み合わせた症例の治療成績

    葛谷 貞二, 石上 雅敏, 伊藤 隆徳, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 石津 洋二, 本多 隆, 林 和彦, 石川 哲也, 後藤 秀実

    日本消化器病学会雑誌   Vol. 112 ( 臨増大会 ) page: A871 - A871   2015.9

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  63. DC beadを用いたTACEの臨床的検討 cTACEとの比較

    今井 則博, 石上 雅敏, 伊藤 隆徳, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 阿知波 宏一, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石川 哲也, 廣岡 芳樹, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.2 ) page: A737 - A737   2015.9

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  64. 探針エレクトロスプレー/タンデム質量分析(PESI/MS/MS)によるマウス肝臓内のメタボローム直接分析法(インタクト・メタボローム分析法)の構築

    林 由美, 財津 桂, 村田 匡, 大原 倫美, 中切 健太, 草野 麻衣子, 那須 民江, 中島 宏樹, 石川 哲也, 土橋 均, 石井 晃

    JSBMS Letters   Vol. 40 ( Suppl. ) page: 65 - 65   2015.8

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    Language:Japanese   Publisher:(一社)日本医用マススペクトル学会  

  65. C型肝炎治療の現状について

    石川 哲也

    明日の臨床   Vol. 27 ( 1 ) page: 29 - 34   2015.6

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    Language:Japanese   Publisher:愛知県保険医協会  

  66. 高齢者C型肝炎におけるDaclatasvir・Asunaprevir併用療法の治療早期の効果

    本多 隆, 石上 雅敏, 伊藤 隆徳, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 石津 洋二, 葛谷 貞二, 林 和彦, 中野 功, 石川 哲也, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.1 ) page: A504 - A504   2015.4

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  67. 当院におけるDC Beadの初期使用経験

    今井 則博, 石上 雅敏, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 阿知波 宏一, 山田 恵一, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石川 哲也, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.1 ) page: A533 - A533   2015.4

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  68. 超音波による放射線治療・化学療法の効果判定 当院での進行肝細胞癌に対するソラフェニブ治療における造影超音波検査の現状と役割

    葛谷 貞二, 石上 雅敏, 石津 洋二, 本多 隆, 林 和彦, 石川 哲也, 後藤 秀実

    超音波医学   Vol. 42 ( Suppl. ) page: S277 - S277   2015.4

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    Language:Japanese   Publisher:(公社)日本超音波医学会  

  69. コリン欠乏高脂肪食によるNASHマウスモデルにおける高血糖を伴わない脂質、分岐鎖アミノ酸代謝の検討

    本多 隆, 石上 雅敏, 馬 凌云, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, Luo Fangqiong, 山田 恵一, 石津 洋二, 葛谷 貞二, 林 和彦, 中野 功, 石川 哲也, 後藤 秀実

    糖尿病   Vol. 58 ( Suppl.1 ) page: S - 481   2015.4

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  70. 消化管ホルモンの役割を見直す 摂食行動と栄養代謝調節 高齢者食欲不振の病態における食欲関連ホルモン炎症・免疫応答の役割について

    石川 哲也, 林 由美, 松浦 俊博

    日本消化器病学会雑誌   Vol. 112 ( 臨増総会 ) page: A98 - A98   2015.3

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Presentations 120

  1. 肝再生不全マウスに対する肝細胞移植後の肝内環境変化と肝再生との関連について

    玉置優貴、堀純子、内藤沙妃、柴田ゆりあ、池田悠馬、名仁澤英里、林由美、石川哲也

    第68回日本臨床検査医学会学術集会  2021.11.12 

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    Event date: 2021.11

    Language:Japanese   Presentation type:Poster presentation  

    Venue:富山   Country:Japan  

  2. HBs抗原のヒト肝細胞への取込み機序とその意義について

    堀純子、玉置優貴、内藤沙妃、柴田ゆりあ、池田悠馬、名仁澤英里、林由美、石川哲也

    第68回日本臨床検査医学会学術集会  2021.11.12 

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    Event date: 2021.11

    Language:Japanese   Presentation type:Poster presentation  

    Venue:富山   Country:Japan  

  3. 食餌性因子が肝内の免疫・ストレス応答と肝障害感受性に及ぼす影響について

    内藤沙妃、玉置優貴、堀純子、柴田ゆりあ、池田悠馬、名仁澤英里、林由美、石川哲也

    第68回日本臨床検査医学会学術集会  2021.11.12 

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    Event date: 2021.11

    Language:Japanese   Presentation type:Poster presentation  

    Venue:富山   Country:Japan  

  4. SA-5, a novel oral agonist of Toll-like receptor (TLR) 7, induces HBs antigen specific immune reaction in chronic HBV infection model mice.

    Takayasu Ideta, Hiroyasu Ito, Tetsuya Ishikawa.

    2021.11.4 

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    Event date: 2021.11

    Language:English   Presentation type:Symposium, workshop panel (public)  

    Country:Japan  

  5. 肝細胞移植後の肝再生過程における肝内環境変化とその役割について

    玉置優貴、林由美、石川哲也

    第42回日本炎症・再生医学会  2021.7.7 

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    Event date: 2021.7

    Language:Japanese   Presentation type:Poster presentation  

    Venue:オンライン   Country:Japan  

  6. 核酸アナログ治療中止後可能予測因子とHBVコア変異との関係

    本多隆、石上雅敏、山本崇文、犬飼庸介、杉山由晃、吉岡直輝、水野和幸、武藤久哲、横山晋也、山本健太、伊藤隆徳、今井則博、石津洋二、石川哲也、藤城光弘

    第57回日本肝臓学会総会  2021.6.17 

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    Event date: 2021.6

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:札幌   Country:Japan  

  7. 肝細胞キメラマウス作製系における移植肝細胞の生着、拒絶の動態と拒絶回避のための治療について

    玉置 優貴, 堀 純子, 名仁澤 英里, 林 由美, 石川 哲也

    第67回日本臨床検査医学会学術集会  2020.11.20  日本臨床検査医学会

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    Event date: 2020.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:岩手(オンライン)   Country:Japan  

  8. B型肝炎症例におけるテノホビルジソプロキシルフマル酸塩への切替えによるHBV DNA,HBs抗原,ALT値の変化に関する検討

    本多隆, 石上雅敏, 山本崇文, 犬飼庸介, 吉岡直輝, 水野和幸, 武藤久哲, 横山晋也, 田中卓, 山本健太, 伊藤隆徳, 石津洋二, 葛谷貞二, 石川哲也, 藤城光弘

    第56回日本肝臓学会総会  2020.8.28  日本肝臓学会

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    Event date: 2020.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:大阪   Country:Japan  

  9. 非肝癌症例と肝発癌症例の違いに関与する腸内細菌の検討

    本多 隆, 石上 雅敏, 山本 崇文, 犬飼 庸介, 杉山 由晃, 吉岡 直輝, 水野 和幸, 武藤 久哲, 横山 晋也, 田中 卓, 山本 健太, 伊藤 隆徳, 石津 洋二, 葛谷 貞二, 石川 哲也, 藤城 光弘

    第56回日本肝臓学会総会  2020.8.28  日本肝臓学会

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    Event date: 2020.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:大阪   Country:Japan  

  10. 腫瘍肝占拠率50%以上の高度進行肝細胞癌に対する分子標的治療薬の治療効果の検討~ソラフェニブとレンバチニブの比較~ International conference

    武藤久哲, 葛谷貞二, 杉山由晃, 吉岡直輝, 水野和幸, 横山晋也, 田中卓, 山本健太, 伊藤隆徳, 石津洋二, 本多隆, 石川哲也, 石上雅敏, 藤城光弘

    第56回日本肝臓学会総会  2020.8.28 

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    Event date: 2020.8

    Language:Japanese   Presentation type:Oral presentation (general)  

  11. 肝細胞移植後の肝再生過程における肝内環境変化とその役割について

    玉置優貴, 林由美, 石川哲也

    第42回日本炎症・再生医学会  2020.7.8 

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    Event date: 2020.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京(オンライン)   Country:Japan  

  12. 高脂肪食負荷マウスにおける肝障害重症化機序についての解析

    名仁澤英里、玉置優貴、宮下凛太郎、園玲華、鈴木博子、林由美、神戸歩、伊藤弘康、石川哲也

    第59回日本臨床検査医学会 東海・北陸支部総会、第340回日本臨床化学会東海・北陸支部例会  2020.2.23  日本臨床検査医学会 東海・北陸支部、日本臨床化学会東海・北陸支部

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    Event date: 2020.2

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:岐阜   Country:Japan  

  13. 肝細胞キメラマウス作製系における細胞移植後の免疫拒絶応答の解析

    玉置優貴、名仁澤英里、宮下凛太郎、園玲華、鈴木博子、林由美、神戸歩、伊藤弘康、石川哲也

    第59回日本臨床検査医学会 東海・北陸支部総会、第340回日本臨床化学会東海・北陸支部例会  2020.2.23  日本臨床検査医学会 東海・北陸支部、日本臨床化学会東海・北陸支部

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    Event date: 2020.2

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:岐阜   Country:Japan  

  14. B型肝炎ウイルスの生活環におけるエンドサイトーシス経路の役割

    宮下凛太郎、名仁澤英里、園玲華、玉置優貴、林由美、石川哲也

    第66回日本臨床検査医学会学術集会  2019.11.24  日本臨床検査医学会

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    Event date: 2019.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:岡山   Country:Japan  

  15. 肝細胞キメラマウス作製系を用いたアロ肝細胞に対する免疫拒絶反応の解析 International conference

    玉置優貴, 名仁澤英里, 宮下凛太郎, 園玲華, 林由美, 石川哲也

    第66回日本臨床検査医学会学術集会  2019.11.22 

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    Event date: 2019.11

    Language:Japanese   Presentation type:Oral presentation (general)  

  16. 新規HBV感染マウスモデル作製と宿主免疫応答の解析

    神戸歩、伊藤弘康、石川哲也

    第55回日本肝臓学会総会  2019.5.30  日本肝臓学会

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    Event date: 2019.5

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:東京   Country:Japan  

  17. HBVキャリアマウスを用いた核酸製剤による治療的ワクチン療法の開発

    伊藤弘康、石川哲也

    第105回日本消化器病学会総会  2019.5.10  日本消化器病学会

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    Event date: 2019.5

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:金沢   Country:Japan  

  18. Hepatic intracellular stress responsible for the development of HBV-related fulminant hepatitis. International conference

    Nanizawa E, Tamaki Y, Sono R, Miyashita R, Hayashi Y, Ishikawa T.

    APASL Single Topic Conference on Liver Immunology and Genetics  2019.4.19  Asian Pacific Association for the Study of the Liver

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    Event date: 2019.4

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  19. マウス肝障害モデルにおけるトロンボモジュリン遺伝子導入脂肪由来肝細胞の炎症軽減効果について

    山本万智、名仁澤英里、今井田藍、山崎花那子、園玲華、玉置優貴、宮下凛太郎、林由美、石川哲也

    第65回日本臨床検査医学会学術集会  2018.11.17  日本臨床検査医学会

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    Event date: 2018.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  20. B型肝炎ウイルス粒子可視化技術を用いたウイルス生活環の解析

    今井田藍、山崎花那子、山本万智、名仁澤英里、玉置優貴、宮下凛太郎、園玲華、林由美、石川哲也

    第65回日本臨床検査医学会学術集会  2018.11.18  日本臨床検査医学会

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    Event date: 2018.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  21. B型肝炎ウイルス粒子の蛍光ラベルによる可視化と細胞内取込み機構の解析

    山崎花那子、今井田藍、名仁澤英里、山本万智、宮下凛太郎、玉置優貴、園玲華、林由美、石川哲也

    第65回日本臨床検査医学会学術集会  2018.11.18  日本臨床検査医学会

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    Event date: 2018.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  22. 探針エレクトロスプレーイオン化タンデム質量分析(PESI/MS/MS)とScheduled SRM法を用いた生体組織のインタクト・メタボロミクス法の構築

    近藤健太、林由美、村田匡、土屋弥月、大原倫美、石川哲也、緒方是嗣、土橋均、石井晃、財津桂

    第43回日本医用マススペクトル学会年会  2018.9.6  日本医用マススペクトル学会

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    Event date: 2018.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:札幌   Country:Japan  

  23. 探針エレクトロスプレーイオン化タンデム質量分析(PESI/MS/MS)を用いたin vivoリアルタイム・モニタリングシステムの構築

    林由美、財津桂、村田匡、土橋均,石井晃、緒方是嗣、石川哲也

    第43回日本医用マススペクトル学会年会  2018.9.6  日本医用マススペクトル学会

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    Event date: 2018.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:札幌   Country:Japan  

  24. 量子ドットイメージング技術を用いた移植幹細胞と免疫細胞のinteraction 機構解明

    北村晃大、湯川博、佐藤和秀、有本知子、小野島大介、石川哲也、馬場嘉信

    第39回日本炎症・再生医学会  2018.7.11 

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    Event date: 2018.7

    Language:Japanese   Presentation type:Poster presentation  

    Venue:東京   Country:Japan  

  25. iPS細胞由来肝様細胞に対する量子ドットを用いたラベル化手法の確立と移植後のin vivoイメージング

    名仁澤英里、林由美、湯川博、石川哲也

    第39回日本炎症・再生医学会  2018.7.11  日本炎症・再生医学会

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    Event date: 2018.7

    Language:Japanese   Presentation type:Poster presentation  

    Venue:東京  

  26. 進行肝細胞癌に対するレゴラフェニブ投与後早期(6週間以内)の治療成績 -ソラフェニブ導入時との比較- International conference

    葛谷貞二, 石上雅敏, 武藤久哲, 横山晋也, 田中卓, 山本健太, 安藤祐資, 伊藤隆徳, 安田諭, 石津洋二, 本多隆, 林和彦, 石川哲也, 廣岡芳樹, 後藤秀実

    第54回日本肝臓学会総会  2018.6.15 

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    Event date: 2018.6

    Language:Japanese   Presentation type:Poster presentation  

  27. 進行肝細胞癌に対するソラフェニブ投与後の肝予備能推移 -初回画像PD判定時にレゴラフェニへの切り替え条件を満たすかにも注目して- International conference

    葛谷貞二, 石上雅敏, 武藤久哲, 横山晋也, 田中卓, 山本健太, 安藤祐資, 伊藤隆徳, 安田諭, 石津洋二, 本多隆, 林和彦, 石川哲也, 廣岡芳樹, 後藤秀実

    第104回日本消化器病学会総会  2018.4.19 

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    Event date: 2018.4

    Language:Japanese   Presentation type:Oral presentation (general)  

  28. 線維化進展例におけるIFNフリー抗HCV治療の効果-IFN時代と比較して何が変わったか? International conference

    石上雅敏, 安藤祐資, 林和彦, 本多隆, 葛谷貞二, 石津洋二, 伊藤隆徳, 安田諭, 山本健太, 田中卓, 横山晋也, 中野功, 石川哲也, 後藤秀実

    第21回日本肝臓学会大会  2017.10.13 

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    Event date: 2017.10

    Language:Japanese   Presentation type:Poster presentation  

  29. Rapid-fire direct metabolome analysis by probe electrospray ionization/tandem mass spectrometry: its preclinical applications to validate the methods. International conference

    Hayashi Y, Zaitsu K, Murata T, Ohara T, Kondo K, Kusano M, Ogata K, Tsuchihashi H, Tanihata H, Ishii A, Ishikawa T.

    The 4th Annual European Congress of the Association for Mass Spectrometry: Application to the Clinical Lab  2017.9.10  European Congress of the Association for Mass Spectrometry

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    Event date: 2017.9

    Language:English   Presentation type:Poster presentation  

    Venue:Salzburg   Country:Austria  

  30. 門脈腫瘍栓を伴う進行肝細胞癌に対するソラフェニブの治療成績-6週PD判定の有無に着目して- International conference

    葛谷貞二, 石上雅敏, 横山晋也, 田中卓, 山本健太, 安藤祐資, 伊藤隆徳, 安田諭, 野村彩, 石津洋二, 本多隆, 林和彦, 石川哲也, 廣岡芳樹, 後藤秀実

    第53回日本肝臓学会総会  2017.6.8 

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    Event date: 2017.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  31. マウスモデルを使用した慢性B型肝炎に対する治療用ワクチン開発の試み

    伊藤弘康、清島満、石川哲也

    第53回日本肝臓学会総会  2017.6.9  日本肝臓学会

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    Event date: 2017.6

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:広島   Country:Japan  

  32. C型慢性肝炎における線維化進展例(Fib4 index≧3.25)におけるウイルス焼失後の肝予備能の変化 International conference

    石上雅敏, 林和彦, 本多隆, 葛谷貞二, 石津洋二, 野村彩, 伊藤隆徳, 安田諭, 安藤祐資, 山本健太, 田中卓, 横山晋也, 石川哲也, 中野功, 廣岡芳樹, 後藤秀実

    第53回日本肝臓学会総会  2017.6.9 

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    Event date: 2017.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  33. マウスモデルを使用した慢性B型肝炎に対する治療用ワクチン開発の試み International conference

    伊藤弘康, 清島満, 石川哲也

    第53回日本肝臓学会総会  2017.6.9 

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    Event date: 2017.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  34. 歯髄幹細胞無血清培養上清による難治性肝疾患での有用性の検討-急性・慢性肝炎動物モデルにおける効果発現メカニズムの違いに着目して International conference

    伊藤隆徳, 田中卓, 山本健太, 安藤祐資, 安田諭, 野村彩, 加藤幸一郎, 石津洋二, 葛谷貞二, 本多隆, 林和彦, 石上雅敏, 廣岡芳樹, 石川哲也, 後藤秀実

    第53回日本肝臓学会総会  2017.6.8 

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    Event date: 2017.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  35. 慢性肝疾患患者における生活習慣による腸内細菌への影響 International conference

    山本健太, 石上雅敏, 田中卓, 安藤祐資, 伊藤隆徳, 安田諭, 野村彩, 加藤幸一郎, 石津洋二, 葛谷貞二, 本多隆, 林和彦, 廣岡芳樹, 石川哲也, 後藤秀実

    第53回日本肝臓学会総会  2017.6.8 

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    Event date: 2017.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  36. High-throughput Intact Metabolome Analysis of Mouse Biological Specimens by Probe Electrospray Ionization/Tandem Mass Spectrometry (PESI/MS/MS).

    Hayashi Y, Zaitsu K, Murata T, Baba S, Ohara T, Moreau S, Kusano K, Nakajima H, Tanihata H, Tsuchihashi H, Ishii A, Ishikawa T.

    65th Conference of American Society for Mass Spectrometry.  2017.6.5  American Society for Mass Spectrometry

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    Event date: 2017.6

    Language:English   Presentation type:Poster presentation  

    Venue:Indianapolis, Indiana   Country:United States  

  37. Development of an in vivo real-time monitoring system using probe electrospray ionization/tandem mass spectrometry (PESI/MS/MS) and its preliminary applications. International conference

    Zaitsu K, Hayashi Y, Murata T, Ohara T, Moreau S, Kusano M, Nakajima H, Tanihata H, Tsuchihashi H, Ishikawa T, Ishii A.

    65th Conference of American Society for Mass Spectrometry.  2017.6.5  American Society for Mass Spectrometry

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    Event date: 2017.6

    Language:English   Presentation type:Poster presentation  

    Venue:Indianapolis, Indiana   Country:United States  

  38. 量子ドットによる移植幹細胞in vivo蛍光リアルタイムイメージング

    湯川博、吉住寧真、有本知子、石川哲也、馬場嘉信

    第16回日本再生医療学会総会  2017.3.7  日本再生医療学会

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    Event date: 2017.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:仙台   Country:Japan  

  39. 量子・磁気ナノハイブリッド材料を用いた幹細胞イメージングおよびハイパーサーミア効果

    小林香央里、湯川博、村田勇樹、城潤一郎、小野島大介、山本雅哉、石川哲也、田畑泰彦、馬場嘉信

    第16回日本再生医療学会総会  2017.3.8  日本再生医療学会

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    Event date: 2017.3

    Language:Japanese   Presentation type:Poster presentation  

    Venue:仙台   Country:Japan  

  40. Direct drug analysis in serum by probe electrospray ionization/tandem mass spectrometry and its preliminary application to a real-time metabolism study.

    Zaitsu K, Hayashi Y, Kusano M, Hisatsune K, Ohara T, Murata T, Nakajima H, Tanihata H, Tsuchihashi H, Ishikawa T, Ishii A.

    The 9th Annual European Congress of the Association for Mass Spectrometry: Application to the Clinical Lab  2017.1.22  European Congress of the Association for Mass Spectrometry

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    Event date: 2017.1

    Language:English   Presentation type:Poster presentation  

    Venue:Palm Springs, CA   Country:United States  

  41. 量子ドットを用いた移植肝細胞の蛍光イメージング

    奥村啓樹、名仁澤英里、中西杏菜、坡下真大、湯川博、馬場嘉信、石川哲也、松永民秀

    第39回日本分子生物学会年会  2016.11.29  日本分子生物学会

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    Event date: 2016.11

    Language:Japanese   Presentation type:Poster presentation  

    Venue:横浜   Country:Japan  

  42. Analysis of cellular intrution mechanism of hepatitis B virus using novel method of viral paticle labeling. International conference

    FumikaHirano, Eri Nanizawa, Yumi Hayashi, Hiroshi Yukawa, Yoshinobu Baba, Tetsuya Ishikawa.

    2016 Nagoya-Yonsei University Research Exchange Meeting on Health Sciences  2016.11.3  Nagoya University, Yonsei University

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    Event date: 2016.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  43. CpG oligonucleotides complexed with dectin-1 ligand enhances humoral and cellular immune response to HBV vaccine

    Hiroyasu Ito, Motohiro Nakamura, Hidekazu Ishida, Kouji Kobiyama, Takuya Yamamoto, Ken J. Ishii, Mitsuru Seishima, Tetsuya Ishikawa.

    23rd International Symposium on Hepatitis C Virus and Related Viruses  2016.10.13 

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    Event date: 2016.10

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  44. Real-time monitoring of glutamic acid in mouse brain by direct coupling of microdialysis to tandem MS with the newly developed on-line desalting system International conference

    Kei Zaitsu, Yumi Hayashi, Hiroaki Kanayama, Ryosuke Takagi, Saki Noda, Maiko Kusano, Toshikazu Minohata, Jun-ichi Azuma, Nobuhiro Kanayama, Tetsuya Ishikawa, Hitoshi Tsuchihashi, Akira Ishii

    The 3rd Annual European Congress of the Association for Mass Spectrometry: Application to the Clinical Lab  2016.9.12  Association for Mass Spectrometry

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    Event date: 2016.9

    Language:English   Presentation type:Poster presentation  

    Country:Austria  

  45. Application of intact metabolome analysis by probe electrospray ionization (PESI)/MS/MS to local distribution analysis and in vivo real-time monitoring. International conference

    Hayashi Y, Zaitsu K, Murata T, Nakajima H, Kusano M, Tsuchihashi H, Ishii A, Ishikawa T.

    The 3rd Annual European Congress of the Association for Mass Spectrometry: Application to the Clinical Lab  2016.9.12  Association for Mass Spectrometry

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    Event date: 2016.9

    Language:English   Presentation type:Poster presentation  

    Venue:Salzburg   Country:Austria  

  46. 新規磁性ナノ粒子による幹細胞in vivoイメージング技術の確立

    名仁澤英里、湯川博、荻原裕祐、平野文香、林由美、齋藤弘明、加藤一郎、石川哲也、馬場嘉信

    第40回日本鉄バイオサイエンス学会学術集会  2016.9.10  日本鉄バイオサイエンス学会

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    Event date: 2016.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋   Country:Japan  

  47. Intact metabolome analysis of mice biological tissues by probe electrospray ionization- tandem mass spectrometry (PESI-MS/MS) and its application to real-time analysis International conference

    Yumi Hayashi, Kei Zaitsu, TasukuMurata, Hiroki Nakajima, Maiko Kusano, Hitoshi Tsuchihashi, Akira Ishii, Tetsuya Ishikawa

    Royal Society of Chemistry Tokyo International Conference 2016  2016.9.8 

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    Event date: 2016.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  48. Anorexia in the elderly and its association with latent inflammation. The roles of inflammatory cytokines and appetite-related hormones in the pathogenesis of anorexia of aging. International conference

    Fumika Hirano, Eri Nanizawa, Yumi Hayashi, Toshihiro Matsuura, Tetsuya Ishikawa

    The 32nd World Congress of Biomedical Laboratory Sciences  2016.9.2 

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    Event date: 2016.8 - 2016.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  49. C型肝炎ウイルスの構造と複製および病原性発現機構 Invited

    石川哲也

    第39回東海薬物治療研究会  2016.7.16  東海薬物治療研究会

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    Event date: 2016.7

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:名古屋  

  50. B型肝炎ウイルス粒子の可視化による細胞内侵入機構の解析

    第23回肝細胞研究会  2016.7.8  肝細胞研究会

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    Event date: 2016.7

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:大阪   Country:Japan  

  51. マウス急性肝障害モデルにおける脂肪由来幹細胞移植後の生体内動態解析

    名仁澤英里、吉住寧真、平野文香、林由美、湯川博、馬場嘉信、石川哲也

    第37回日本炎症・再生医学会  2016.6.17 

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    Event date: 2016.6

    Language:Japanese   Presentation type:Poster presentation  

    Venue:京都   Country:Japan  

  52. 量子ドットによる高効率幹細胞ラベリング手法の構築

    湯川博、石川哲也、馬場嘉信

    第37回日本炎症・再生医学会  2016.6.17  日本炎症・再生医学会

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    Event date: 2016.6

    Language:Japanese   Presentation type:Poster presentation  

    Venue:京都   Country:Japan  

  53. The changes of hepatitis C virus-specific immune responses during daclatasvir and asunaprevir therapy. International conference

    Koichiro Kato, Masatoshi Ishigami, Yoji Ishizu, Tetsuya Ishikawa, Takaji Wakita, Hidemi Goto

    2016 APASL Single Topic Conference on Hepatitis C  2016.6.11  Asian Pacific Association for the Study of the Liver

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    Event date: 2016.6

    Language:English   Presentation type:Oral presentation (general)  

    Venue:Kaohsiung   Country:Taiwan, Province of China  

  54. Intact metabolome analysis of mice biological tissues by probe electrospray ionization-tandem mass spectrometry and its preliminary application to real-time analysis. International conference

    Zaitsu K, Hayashi Y, Murata T, Nakajima H, Ishikawa T, Kusano M, Tsuchihashi H, Ishii A.

    64th Conference of American Society for Mass Spectrometry  2016.6.7  American Society for Mass Spectrometry

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    Event date: 2016.6

    Language:English   Presentation type:Oral presentation (general)  

    Venue:San Antonio, TX   Country:United States  

  55. B型肝炎ウイルス粒子可視化による細胞内侵入機構の解析

    石川哲也、湯川博

    第52回日本肝臓学会総会  2016.5.19  日本肝臓学会

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    Event date: 2016.5

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:千葉   Country:Japan  

  56. ダクラタスビル+アスナプレビル治療症例におけるHCV抗原特異的免疫応答の変化について

    加藤幸一郎、石川哲也、石津洋二、荒川恭宏、安藤祐資、伊藤隆徳、安田諭、川口彩、新家卓郎、今井則博、葛谷貞二、本多隆、林和彦、石上雅敏、後藤秀実

    第52回日本肝臓学会総会  2016.5.20  日本肝臓学会

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    Event date: 2016.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:千葉   Country:Japan  

  57. 新規CpG ODNアジュバンドを用いたHBV 持続感染症に対するワクチン療法の開発

    伊藤弘康、石川哲也

    第26回抗ウイルス療法学会  2016.5.15  抗ウイルス療法学会

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    Event date: 2016.5

    Language:Japanese  

    Venue:名古屋   Country:Japan  

  58. 薬物性肝障害 Invited

    石川哲也

    日本消化器病学会・ポストグラデュエイトコース  2016.4.23  日本消化器病学会

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    Event date: 2016.4

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:東京   Country:Japan  

  59. 新規CpG ODNアジュバンドによるHBV 特異的免疫誘導能の検討

    伊藤弘康、石川哲也、清島満

    第102回日本消化器病学会総会  2016.4.21  日本消化器病学会

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    Event date: 2016.4

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:東京   Country:Japan  

  60. NIR-II近赤外領域における移植幹細胞in vivoイメージング

    湯川博、小野島大介、新岡宏彦、三宅淳、石川哲也、馬場嘉信

    第15回日本再生医療学会総会  2016.3.18  日本再生医療学会

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    Event date: 2016.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:大阪   Country:Japan  

  61. 最先端量子技術に基づく移植幹細胞in vivo蛍光リアルタイムイメージング

    湯川博、吉住寧真、大原倫美、石川哲也、馬場嘉信

    第15回日本再生医療学会総会  2016.3.18  日本再生医療学会

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    Event date: 2016.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:大阪   Country:Japan  

  62. Adipose-derived stem cell administration for cytotoxic T lymphocyte-mediated liver injury in mice. International coauthorship International conference

    Kenta Nakagiri, Tomomi Ohara, Fumika Hirano, Eri Nanizawa, Yumi Hayashi, Masatoshi Ishigami, Hiroshi Yukawa, Tetsuya Ishikawa

    25th Conference of the Asian Pacific Association for the Study of the Liver  2016.2.21  Asian Pacific Association for the Study of the Liver

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    Event date: 2016.2

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  63. Therapeutic effects of ghrelin and leptin on experimental acute liver injury in mice.

    Tomomi Ohara, Kenta Nakagiri, Eri Nanizawa, Fumika Hirano, Yumi Hayashi, Hiroshi Yukawa, Tetsuya Ishikawa

    25th Conference of the Asian Pacific Association for the Study of the Liver  2016.2.23  Asian Pacific Association for the Study of the Liver

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    Event date: 2016.2

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  64. ダクラタスビル+アスナプレビル治療中のHCV抗原特異的免疫応答の変化について

    加藤幸一郎、荒川恭弘、石川哲也、安藤祐資、伊藤隆徳、安田諭、川口彩、新家卓郎、今井則博、阿知波宏一、石津洋二、葛谷貞二、本多隆、林和彦、石上雅敏、脇田隆字、後藤秀実

    第41回日本肝臓学会西部会  2015.12.3  日本肝臓学会

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    Event date: 2015.12

    Language:Japanese  

    Venue:名古屋   Country:Japan  

  65. 脂肪由来幹細胞が細胞傷害性Tリンパ球機能に与える影響について

    中切健太、大原倫美、平野文香、名仁澤英里、林由美、石川哲也

    第62回日本臨床検査医学会学術集会  2015.11.21  日本臨床検査医学会

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    Event date: 2015.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京  

  66. レプチンが脂肪由来幹細胞の分化能に与える影響について

    大原倫美、中切健太、平野文香、名仁澤英里、林由美、石川哲也

    第62回日本臨床検査医学会学術集会  2015.11.21  日本臨床検査医学会

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    Event date: 2015.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  67. NIR-II近赤外領域における移植幹細胞in vivo 蛍光イメージング

    湯川 博、小野島大介、新岡宏彦、竹内 司、大谷敬亨、大谷敬亨、大谷敬亨、大谷敬亨、大谷敬亨、三宅 淳、石川哲也、馬場嘉信

    第37回バイオマテリアル学会  2015.11.9  バイオマテリアル学会

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    Event date: 2015.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:京都   Country:Japan  

  68. Influence of adipose-derived stem cell administration on cytotoxic T lymphocyte-mediated liver injury in mice International conference

    Kenta Nakagiri, Tomomi Ohara, Eri Nanizawa, Fumika Hirano, Yumi Hayashi, Tetsuya Ishikawa.  2015.11.6  Nagoya University, Yonsei University

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    Event date: 2015.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Korea, Republic of  

  69. マウス急性肝障害モデルにおける移植後脂肪由来幹細胞の生体内動態解析

    石川哲也、吉住寧真、湯川博

    第19回肝臓学会大会  2015.10.8  日本肝臓学会

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    Event date: 2015.10

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:東京   Country:Japan  

  70. 探針エレクトロスプレー/タンデム質量分析(PESI/MS/MS)によるマウス肝臓内のメタボローム直接分析法(インタクト・メタボローム分析法)の構築

    林 由美、財津 桂、村田 匡、大原 倫美、中切 健太、草野 麻衣子、那須 民江、中島 宏樹、石川 哲也、土橋 均、石井 晃

    第40回日本医用マススペクトル学会年会  2015.9.17  日本医用マススペクトル学会

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    Event date: 2015.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:浜松   Country:Japan  

  71. Intact metabolome analysis of mice liver by probe electrospray ionization-tandem mass spectrometry (PESI-MS/MS). International conference

    Hayashi Y, Zaitsu K, Murata T, Nakajima H, Nakajima T, Tsuchihashi H, Ishii A, Ishikawa T.

    63rd ASMS Conference on Mass Spectrometry and Allied Topics  2015.6.4 

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    Event date: 2015.6

    Language:English   Presentation type:Poster presentation  

    Venue:St. Louis, Missouri   Country:United States  

  72. 高齢者食欲不振の病態における食欲関連ホルモン、炎症・免疫応答の役割について

    石川哲也、林由美、松浦俊博

    第101回日本消化器病学会総会  2015.4.23  日本消化器病学会

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    Event date: 2015.4

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:仙台   Country:Japan  

  73. NRI-IIイメージングシステムによる移植幹細胞in vivoイメージング

    湯川博、大林桃子、中川伸吾、吉住寧真、小野島大介、新岡宏彦、竹内司、大谷敬亨、三宅淳、石川哲也、馬場嘉信

    第14回日本再生医療学会総会 

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    Event date: 2015.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:横浜   Country:Japan  

  74. カドミウムフリー量子ドットを用いた幹細胞ラベリングの評価とin vivoイメージング

    荻原裕祐、湯川博、石神裕二郎、吉住寧真、中川伸吾、大原倫美、亀山達矢、小野島大介、島本司、石川哲也、馬場嘉信

    第14回日本再生医療学会総会 

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    Event date: 2015.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:横浜   Country:Japan  

  75. 新規磁性ナノ粒子による量子ドット幹細胞ラベリング手法の構築と移植幹細胞マルチモーダルイメージング

    湯川博、荻原裕祐、筒井陽子、中川伸吾、吉住寧真、小野島大介、斎藤弘明、加藤一郎、石川哲也、馬場嘉信

    第14回日本再生医療学会総会 

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    Event date: 2015.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:横浜   Country:Japan  

  76. マウス急性肝障害モデルにおけるグレリンの炎症軽減効果について

    中川伸吾、吉住寧真、中切健太、大原倫美、松浦俊博、石川哲也

    第61回日本臨床検査医学会学術集会 

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    Event date: 2014.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:福岡   Country:Japan  

  77. The decrease of alpha-fetoprotein and/or the decrease of tumor stain on contrast enhanced CT images after 2 weeks of sorafenib treatment predict prognosis in patients with advanced hepatocellular carcinoma. International conference

    KUZUYA Teiji, ISHIGAMI Masatoshi, ISHIZU Yoji, HONDA Takashi, HAYASHI Kazuhiko, ISHIKAWA Tetsuya, GOTO Hidemi

    The 65th Annual Meeting of American association for the Study of the Liver Diseases 

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    Event date: 2014.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  78. C型肝炎の最新の治療法について Invited

    石川哲也

    愛知県保険医協会 内科臨床研究会  2014.11.1  愛知県医師会

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    Event date: 2014.11

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:名古屋   Country:Japan  

  79. マウスNASHモデルに対してDSS投与による線維化と発癌モデル作成の試み

    阿知波宏一、本多隆、F. Luo、加藤幸一郎、新家卓郎、今井則博、山田恵一、荒川恭宏、石津洋二、葛谷貞二、林和彦、石上雅敏、石川哲也、後藤秀実

    第18回日本肝臓学会大会 

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    Event date: 2014.10

    Language:Japanese   Presentation type:Poster presentation  

    Venue:神戸   Country:Japan  

  80. 高齢者C型慢性肝炎におけるPegIFN・Ribavirin・Simeprevir 3剤併用療法の治療効果

    本多隆、石上雅敏、加藤幸一郎、新家卓郎、今井則博、阿知波宏一、荒川恭宏、山田恵一、石津洋二、葛谷貞二、林和彦、中野功、石川哲也、後藤秀実

    第18回日本肝臓学会大会 

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    Event date: 2014.10

    Language:Japanese   Presentation type:Poster presentation  

    Venue:神戸   Country:Japan  

  81. 知っておきたいB型肝炎のこと Invited

    石川哲也

    中日健康フェア2014  2014.9.7  中日新聞社

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    Event date: 2014.9

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:名古屋   Country:Japan  

  82. 当院においてIsoniazidにより発症した薬物性肝障害の現状

    綾田穣、石川哲也、堀田直樹

    日本消化器病学会東海支部第120回例会 

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    Event date: 2014.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:岐阜   Country:Japan  

  83. 初診時IgM-HA抗体が陰性であったA型重症肝炎の一例

    今井則博、石上雅敏、加藤幸一郎、阿知波宏一、荒川恭宏、山田恵一、石津洋二、葛谷貞二、本多隆、林和彦、石川哲也、後藤秀実

    日本消化器病学会東海支部第120回例会 

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    Event date: 2014.6

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:岐阜   Country:Japan  

  84. C型慢性肝炎難治例におけるPegIFN・Ribavirin・Telaprevir 3剤併用療法の治療効果

    本多隆、石上雅敏、新家卓郎、今井則博、阿知波宏一、荒川恭宏、山田恵一、中野聡、石津洋二、葛谷貞二、林和彦、中野功、石川哲也、片野義明、後藤秀実

    第50回日本肝臓学会総会 

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    Event date: 2014.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  85. C型慢性肝炎患者に対するペグインターフェロンα2b・リバビリン療法無効例におけるcore、NS3、NS5A領域のアミノ酸変異の変化について

    林和彦、石上雅敏、新家卓郎、今井則博、阿知波宏一、荒川恭宏、山田恵一、中野聡、石津洋二、葛谷貞二、本多隆、石川哲也、片野義明、後藤秀実

    第50回日本肝臓学会総会 

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    Event date: 2014.5

    Language:Japanese   Presentation type:Poster presentation  

    Venue:東京   Country:Japan  

  86. 卵巣摘出NASHマウスに対するRaloxifeneの効果

    Fangqiong LUO、石上雅敏、新家卓郎、今井則博、阿知波宏一、荒川恭宏、山田恵一、中野聡、石津洋二、葛谷貞二、本多隆、林和彦、中野功、石川哲也、後藤秀実

    第50回日本肝臓学会総会 

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    Event date: 2014.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  87. 肝臓特異的UBXD8ノックアウトマウス表現型の検討

    今井則博、鈴木倫毅、新家卓郎、阿知波宏一、荒川恭宏、山田恵一、中野聡、石津洋二、葛谷貞二、本多隆、林和彦、石上雅敏、石川哲也、藤本豊士、後藤秀実

    第50回日本肝臓学会総会 

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    Event date: 2014.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  88. マウス急性肝障害モデルにおける脂肪由来幹細胞(ASC)の炎症制御効果について

    吉住寧真、加納由貴、加納綾乃、中川伸吾、山田達也、湯川博、石川哲也

    第13回日本再生医療学会総会 

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    Event date: 2014.3

    Language:Japanese   Presentation type:Poster presentation  

    Venue:京都   Country:Japan  

  89. 薬物性肝障害の基礎と臨床 Invited

    石川哲也

    平成25年度日本肝臓学会後期教育講演会プログラム  2013.12.7  日本肝臓学会

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    Event date: 2013.12

    Language:Japanese  

    Venue:岐阜   Country:Japan  

  90. Effect of adipose-derived stromal cells on concanavalin A-induced acute liver injury in mice. International conference

    YOSHIZUMI Yasuma, KANO Yuki, KANO Ayano, IWAKI Ryoji, FUJINAKA Sanae, ISHIKAWA Tetsuya

    2013 Yonsei-Nagoya University Research Exchange Meeting on Health Sciences 

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    Event date: 2013.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

    We evaluated therapeutic effect of murine adipose-derived stromal cells (ASC) on concanavalin A (Con A)-induced acute liver injury in mice, which is the model of fulminant hepatic failure (FHF). ASC therapy reduced ALT levels in the treated mice, and is suggested to have great potential in FHF treatment. More detailed analyses are necessary to elucidate the mechanisms of effect of ASC on immunomodulation.

  91. ヒト肝癌細胞株間での各種炎症刺激に対するケモカイン産生能の比較

    山田達也、中川伸吾、吉住寧真、加納由貴、加納綾乃、石川哲也

    第60回日本臨床検査医学会学術集会 

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    Event date: 2013.10 - 2013.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:神戸   Country:Japan  

    ヒト肝細胞の代替として3種類のヒト肝癌細胞株を用い、各種サイトカイン刺激時に惹起されるについて炎症・免疫応答についてケモカイン産生を中心に比較検討し、同種の実験系におけるヒト肝癌細胞株の有用性について検証した。各細胞株で、細胞自身が炎症を増幅する方向に作用していた。ただし、刺激時の発現増強パターンなどには差も認めた。同種の実験系へのヒト肝癌細胞株の使用は有用であるものの、複数の細胞株で同様の検証を行うなど、反応の普遍性について注意深く検討する必要があると考えられた。

  92. 高齢者食欲不振と免疫・ホルモン環境の変化との関連について

    加納綾乃、吉住寧真、中川伸吾、加納由貴、山田達也、松浦俊博、石川哲也

    第60回日本臨床検査医学会学術集会 

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    Event date: 2013.10 - 2013.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:神戸   Country:Japan  

    高齢者食欲不振の原因究明を目的として、高齢者から得られた血液中のサイトカイン、ケモカインに加え、摂食関連ホルモンなどを測定し、臨床データを含めて、食欲不振・低栄養状態の原因となる因子についての解析を行った。解析結果より、食欲不振と炎症性サイトカインであるTNF-αとの関連が示され、高齢者の食欲不振が何らかの慢性炎症を基盤とした病態であることが示唆された。

  93. グレリン、レプチンによる炎症応答制御について

    加納由貴、中川伸吾、吉住寧真、加納綾乃、山田達也、松浦俊博、石川哲也

    第60回日本臨床検査医学会学術集会 

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    Event date: 2013.10 - 2013.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:神戸   Country:Japan  

    グレリン、レプチンの炎症応答への関わりを明確にする目的で、マウス急性肝障害モデルにおいてグレリンとレプチンによる炎症応答制御効果を比較した。グレリンは炎症性サイトカインであるTNF-αなどの産生を抑制し、抗炎症性に働くことで肝障害を軽減した。レプチンは炎症促進作用があると考えられているが、本研究ではレプチンにはグレリンと異なる経路の炎症抑制作用が存在することが示唆された。

  94. インドールアミン酸素添加酵素の発現抑制を用いたHBV特異的細胞障害性T細胞誘導効果の検討

    伊藤弘康、安藤達也、石川哲也、清島満

    第60回日本臨床検査医学会学術集会  2013.11.1  日本臨床検査医学会

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    Event date: 2013.10 - 2013.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:神戸   Country:Japan  

  95. RFAにおける肝癌支援アプリケーションVirtu TRAXの有用性 -とくに2ステップ法によるRFAにおいて-

    葛谷貞二、石上雅敏、今井則博、阿知波宏一、荒川恭弘、山田恵一、中野聡、石津洋二、本多隆、林和彦、石川哲也、後藤秀実

    第49回日本肝癌研究会 

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    Event date: 2013.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋(国際会議場)   Country:Japan  

  96. 肝癌支援アプリケーションVirtu TRAXを用いた経皮的ラジオ波焼灼療術の有用性 -とくに2ステップ法において-

    葛谷貞二、石上雅敏、新家卓郎、今井則博、阿知波宏一、荒川恭弘、山田恵一、中野聡、石津洋二、本多隆、林和彦、石川哲也、後藤秀実

    日本消化器病学会東海支部第118回例会 

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    Event date: 2013.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:浜松   Country:Japan  

  97. 当院におけるDDW-J 2004薬物性肝障害診断基準案を用いた慢性腎臓病合併の有無による薬物性肝障害の検討

    綾田穣、石川哲也、堀田直樹、中野達徳、黒川剛

    日本消化器病学会東海支部第118回例会  2013.6.15  日本消化器病学会東海支部

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    Event date: 2013.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:浜松   Country:Japan  

  98. 当院における薬物性肝障害の現況

    綾田穣、堀田直樹、石川哲也

    第49回日本肝臓学会総会 

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    Event date: 2013.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:東京   Country:Japan  

  99. 高齢(75歳以上)進行肝細胞癌患者に対するソラフェニブ治療の成績

    葛谷貞二、片野義明、今井則博、阿知波宏一、荒川恭弘、山田恵一、中野聡、石津洋二、本多隆、林和彦、石上雅敏、石川哲也、後藤秀実

    第49回日本肝臓学会総会 

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    Event date: 2013.6

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  100. マウスB型急性肝炎モデルにおけるインドールアミン酸素添加酵素の解析

    伊藤弘康、大瀧博文、安藤達也、安藤量基、石川哲也、森脇久隆、清島満

    第49回日本肝臓学会総会 

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    Event date: 2013.6

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

    [目的]急性肝炎はウイルス感染などが原因であり、その一部は劇症化し肝機能不全や意識障害を引き起こす。中でもB型肝炎ウイルスは、劇症化することが他の原因に比べ多いことが知られている。インドールアミン酸素添加酵素 (IDO)は、トリプトファン代謝の律速酵素であり、リンパ球の活性化を抑制し宿主免疫応答を制御していると考えられている。今回、我々はB型肝炎ウイルスタンパクを恒常的に発現するHBVトランスジェニックマウス(HBV-Tg)とIDO欠損マウス(IDO-KO)を掛け合わせHBV-Tg/IDO-KOマウスを樹立し、HBV特異的細胞障害性T細胞(CTL)により誘発される急性肝炎モデルおいてIDOの及ぼす影響について検討した。[方法]HBV特異的CTLをHBV-Tg/IDO-WTマウスおよびHBV-Tg/IDO-KOマウスに経静脈的に投与し肝障害を誘導した。肝障害の評価は、血清中のALT値の測定と病理学的検討にて行った。CTL投与後の肝内でのサイトカインとケモカインのmRNAの発現をリアルタイムPCRを用いて解析した。また、IDO阻害薬である1-メチルトリプトファン(1-MT)やトリプトファンの代謝産物であるキヌレニンの肝障害に及ぼす影響も合わせて検討した。[成績]HBV特異的CTL移入後のHBV-Tg/IDO- WT とHBV-Tg/IDO-KOマウスのALT値を比較すると、HBV-Tg/IDO-KOマウスにてALT値が減少していた。病理学的検討においてもHBV-Tg/IDO- WTマウスにて高度な炎症像が確認された。1-MTを投与することで、CTLによる肝障害が減弱された。サイトカイン及びケモカインのmRNA発現は、HBV-Tg/IDO-KOマウスと比較しHBV-Tg/IDO-WTマウスで増加していた。HBV-Tg/IDO-KOマウスにトリプトファンの代謝産物であるキヌレニンとHBV特異的 CTLを経静脈的に投与したところ肝障害の増悪が認められた。また、IFN-γとキヌレニンをHBV-Tg/IDO-KOマウスに投与したところ、単独の投与では軽度の肝障害のみであったが、同時に投与することにより強い肝障害が誘導された。[考案]HBV-Tg/IDO-KOマウスでは、HBV-Tg/IDO-WTマウスに比べCTL投与による肝障害が減弱することや1-MT投与により肝障害が軽度になることから、IDOの活性化は肝障害を増強していると推測される。今回用いた急性肝炎モデルでは、大量のINF-γを産生することが知られており、産生されたIFN-γとキヌレニンが、肝細胞に直接的に働くことにより、肝障害の悪化が誘発されると考えられた。[結論]今回のマウス急性肝炎モデルでは、IDO活性化は肝障害をより悪化させる可能性があり、IDO活性の阻害はHBV起因性の急性肝障害において有用な治療法の一つになり得ると考えられた。

  101. 当院における薬物性肝障害の現況

    綾田穣、堀田直樹、石川哲也

    第49回日本肝臓学会総会  2013.6.7  日本肝臓学会

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    Event date: 2013.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:東京   Country:Japan  

  102. 進行膵癌に対する活性化リンパ球療法、樹状細胞ワクチン療法の効果ついて

    進行膵癌に対する活性化リンパ球療法、樹状細胞ワクチン療法の効果ついて

    第25回日本バイオセラピィ学会学術集会総会 

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    Event date: 2012.12

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:倉敷   Country:Japan  

    【目的】進行膵癌に対して、ペプチドワクチン療法、樹状細胞ワクチン(DC)療法などの免疫療法が施行されているが、その効果は未だに明確にされていない。我々は、活性化リンパ球(CD3-LAK)療法、CD3-LAK +DC併用療法などの免疫細胞療法を施行された進行膵癌患者を対象に、その治療効果、治療が生存期間に与える影響などについてretrospectiveに解析した。【対象・方法】2004年4月~2012年3月にCD3-LAK療法あるいはCD3-LAK+DC併用療法を施行されたstage 4膵癌患者85例を対象とした。CD3-LAK療法は、末梢血よりリンパ球を分離、固相化抗CD3抗体とrIL-2を加え2週間培養したものを、1あるいは2週間ごと点滴投与した。DC療法は、アフェレーシスによって採取した単球分画に、IL-4、GM-CSF添加(day 1)、TNF-添加(day 5)を行い7日間培養の後、抗原ペプチド(MUC1、CEA、MAGEなど)をパルスしたものを2週間ごとに鼠径部に皮内投与した。累積生存率はKaplan-Meier法を用いて解析した。【成績】CD3-LAK療法を施行されたのは72例、うち2週毎投与67例(LAK-2wk群)、1週毎投与5例(LAK-1wk群)であった。CD3-LAK+DC併用療法は13例(LAK-DC群)に施行された。全85例の平均生存期間(MST)は15か月、1年生存率(1生率) 58.4%、2年生存率(2生率) 24.2%であった。治療法別では、LAK-2wk群:MST 14か月、1生率 55.9%、2生率 18.0%、LAK-DC群:MST 18か月、1生率 75.2%、2生率 37.6%であった。LAK-1wk群は症例数が少なく、1生率のみが評価可能であった(60.0%)。有意差は認めなかったものの、全体との比較で、LAK-DC群での生存率が高い傾向を認めた(p=0.136)。対象患者は、標準化学療法とされるゲムシタビン(GEM)やS-1が投与されたものばかりではなく、化学療法がなされなかった症例も含まれているが、各群におけるMSTは、GEST試験で報告されたGEM投与群の8.8か月、GEM+S-1投与群の10.1か月を上回っていた。【結論】免疫細胞療法は、進行膵癌患者における生命予後の改善に寄与することが示唆された。CD3-LAK +DC併用療法が最も効果が高いこと、ただし、CD3-LAK療法のみでもある程度の生命予後改善効果が得られることが示唆された。

  103. 進行膵癌に対する活性化リンパ球療法、樹状細胞ワクチン療法の効果について

    石川哲也、岩城諒士、藤中沙奈恵、栗本拓也 、吉田松年

    第25回日本バイオセラピィ学会学術集会総会  2012.12.13  日本バイオセラピィ学会

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    Event date: 2012.12

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

  104. 細胞傷害性T細胞により誘発されるマウス劇症肝炎モデルにおけるindoleamine 2,3-dioxygenaseの解析

    安藤達也、大瀧博文、伊藤弘康、星雅人、石川哲也、斉藤邦明、清島満

    第59回日本臨床検査医学会学術集会 

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    Event date: 2012.11 - 2012.12

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:京都   Country:Japan  

    目的:劇症肝炎は、ウイルス感染などが原因となり発生し、急速に進行し肝機能不全や意識障害を引き起こす。なかでも、B型肝炎ウイルスは、劇症肝炎と深い関係があることが知られており、劇症肝炎のみならず、慢性化や肝臓癌に至るまで、重篤な肝疾患に関与している。Indoleamine 2, 3-dioxygenase (IDO)は、トリプトファン代謝の律速酵素であり、その代謝産物であるキヌレニンは、リンパ球の活性化を抑制し、宿主免疫応答を制御していると考えられている。今回、私たちは、B型肝炎ウイルスタンパクを恒常的に発現するHBVトランスジェニックマウス(HBV-Tg)とIDO欠損マウス(IDO-KO)を掛け合わせHBV-Tg/IDO-KOマウスを樹立し、HBV特異的細胞障害性T細胞(HBV-specific CTL)により誘発される劇症肝炎モデルにおけるIDOの及ぼす影響について検討した。
    方法:HBV特異的細胞障害性T細胞(HBV-specific CTL)を、1×106個HBV-Tg/IDO-WTマウスおよびHBV-Tg/IDO-KOマウスそれぞれに経静脈的に接種することにより肝障害を誘導した。肝障害の評価は、血清中のALT濃度と病理学的な検討にて行った。CTLを接種後0、1、2、7日後の肝臓におけるTNF-α、IL-6、IL-10、MCP-1、MIP-2のmRNAの発現は、リアルタイムPCR(Light Cycler 480 system)を用いて、評価した。
    結果:HBV-Tg/IDO- WTマウスに、HBV-specific CTLを投与し、リアルタイムPCRやウエスタンブロットでIDO活性を評価したところ、IDO発現の増加とともに、著しい肝障害が認められた。しかし、HBV-Tg/IDO-KOマウスの血漿中のALT濃度は、減少していることを確認した。さらにIDO阻害剤(1-methyl-D-tryptophan:1-MT)を用い、HBV-specific CTLに及ぼす影響を確認したところ、1-MTを投与することで、CTLによる肝障害が減弱していることを確認できた。また、サイトカイン及びケモカインのmRNA発現は、HBV-Tg/IDO-KOマウスと比較し、HBV-Tg/IDO-WTマウスで増加していた。

  105. ウイルス肝炎治療の現状と展望

    石川哲也

    日本消化器病学会北陸支部 第27回教育講演会 

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    Event date: 2012.6

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:福井   Country:Japan  

    2004年にペグインターフェロンとリバビリンの併用療法が保険収載され、C型慢性肝炎治療の奏功率は大幅に向上した。2011年11月より使用可能となったNS3-4Aプロテアーゼ阻害剤、テラプレビルの併用によりさらに治療効率は向上し、現在、治験が行われているNS3-4Aプロテアーゼ阻害剤とNS5A阻害剤の併用療法の導入により、C型慢性肝炎の撲滅も視野に入るようになった。
    B型慢性肝炎においても、核酸アナログ製剤の導入により、その治療法は劇的に変化した。2000年のラミブジンの保険収載の後、現在までに、アデホビル、エンテカビルの計3剤の核酸アナログ製剤が使用可能となっている。核酸アナログ製剤はB型肝炎ウイルス(HBV)の増殖を強力に抑制し、多くの患者において肝炎の鎮静化、肝病変の進行阻止という効果をもたらす。当初、ラミブジン投与例において、高頻度の耐性株出現が問題となったが、アデホビル、エンテカビルの認可により、状況は大幅に改善された。しかし、投与中止後のウイルスの再増殖、肝炎の再燃という問題は、今も未解決のままである。一旦、核酸アナログ治療を導入すれば明確な中止基準はなく、多くの例で生涯にわたる投与継続を余儀なくされる。核酸アナログ製剤の中止基準の作成が試みられているものの、それを満たす例も少ないと予測される。B型慢性肝炎では、2011年9月にペグインターフェロンの使用も追加承認された。インターフェロンには免疫賦活作用があり、治療が奏功すれば、それによってもたらされるセロコンバージョン、HBV増殖抑制などの効果が長期間にわたって持続するが、ペグインターフェロンを用いた場合でも、そのような効果が得られる確率は必ずしも高くない。HBVの持続感染者の約9割が自然経過でのセロコンバージョン後、healthyキャリアに移行することからもわかるように、HBVの持続的増殖抑制は、宿主免疫応答の活性化によって可能となる。主に、免疫応答賦活を利用した治療法を中心として、今後のB型慢性肝炎治療の展望について論じる。

  106. ウイルス肝炎治療の現状と展望 Invited

    石川哲也

    日本消化器病学会北陸支部 第27回教育講演会  2012.6.17  日本消化器病学会北陸支部

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    Event date: 2012.6

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:福井   Country:Japan  

  107. 当院における多剤薬物併用症例に発症した薬物性肝障害の検討

    綾田穣、堀田直樹、石川哲也

    第48回日本肝臓学会総会 

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    Event date: 2012.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:金沢   Country:Japan  

  108. 進行肝細胞癌に対するソラフェニブ投与後早期の画像上の変化(阻血性変化)と腫瘍マーカーの変化との関連

    葛谷貞二、片野義明、中野聡、増田寛子、及部祐加子、石津洋二、舘佳彦、本多隆、林和彦、石上雅敏、中野功、石川哲也、後藤秀実

    第48回日本肝臓学会総会 

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    Event date: 2012.6

    Language:Japanese   Presentation type:Poster presentation  

    Venue:金沢   Country:Japan  

  109. Late responderに対するペグインターフェロンα2b・リバビリン72週投与の治療効果とcoreとISDR変異、IL-28B一塩基多型の関連についての検討

    土居崎正雄、片野義明、本多隆、林和彦、石上雅敏、石川哲也、中野功、浦野文博、吉岡健太郎、豊田秀徳、熊田卓、山口丈夫、春田純一、後藤秀実

    第48回日本肝臓学会総会 

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    Event date: 2012.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:金沢   Country:Japan  

  110. C型肝炎線維化進展例におけるペグインターフェロン/リバビリン併用療法の発癌抑制効果

    本多隆、片野義明、中野聡、増田寛子、及部祐加子、石津洋二、葛谷貞二、舘佳彦、林和彦、石上雅敏、中野功、石川哲也、後藤秀実

    第48回日本肝臓学会総会 

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    Event date: 2012.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:金沢   Country:Japan  

  111. 進行癌に対するCD3-LAK療法の治療効果関連因子についての検討

    岩城諒士,藤中沙奈恵,山田登美子,石川哲也,吉田松年

    第24回日本バイオセラピィ学会 

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    Event date: 2011.12

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:和歌山   Country:Japan  

    【目的】CD3-LAK療法は種々の進行癌において施行されているものの、その効果は報告によって差があり、治療効果を規定する因子についての解析も十分になされていない。今回、我々は、CD3-LAK療法を施行された進行癌患者において、治療効果(腫瘍縮小効果)について検討し、治療効果に関連する因子の解析を行った。【対象・方法】2008年4月から2010年10月にCD3-LAK療法を施行された進行癌患者81例を対象とした。癌腫の内訳は、肺癌 15例、膵癌 12例、胃癌 11例、肝細胞癌 11例、大腸癌 8例など。Stage分類では、stage 1~3が17名、stage 4が64名。化学療法併用が51名、非併用が30名であった。CD3-LAK療法は、2週間ごとに施行し、6回を1クールとした。1回の治療につき約30mlの末梢血よりリンパ球を分離、KBM540培地に固相化抗CD3抗体とrIL-2(300IU/ml)を加え2週間培養し、3-10x109個の活性化リンパ球を回収、洗浄の後、点滴投与した。1クール前後においてCT検査(胸部・腹部・骨盤部)、血液・血清生化学検査、flow cytometerによる末梢血・培養液中の細胞分画検査、ELISAによる血清サイトカイン測定(TNF-a, IL-6, VEGF, MIC-1)を行った。治療効果(腫瘍縮小効果)はCT画像よりRECIST基準に基づいて判定した。統計解析はSPSS ver.11.0Jを用いて行った。【成績】RECIST基準に基づいた治療効果判定により、SD~PRの49例を治療効果あり群(あり群)、PDの32例を治療効果なし群(なし群)に分類した。次に、治療効果の有無を従属変数とし、年齢、性別、化学療法の有無、stageのほか、各検査値を独立変数とした多変量解析(ロジスティック回帰分析)を行った。治療開始前の検査値を用いた解析では、末梢血リンパ球比率(OR:1.063, 95% CI:1.014-1.115, p=0.011)、血清IFN-濃度(OR:1.040, 95%CI:0.993-1.089, p=0.094)が治療効果に関連していた。治療終了時検査値での解析では、末梢血リンパ球比率(OR:1.068, 95%CI:1.015-1.123, p=0.011)、培養液中CD3-CD56+細胞比率(OR:1.470, 95% CI:0.928-2.329 , p=0.101)が治療効果に関連していた。治療前後の検査値の差を用いた解析では、血清VEGF濃度(OR:0.967, 95% CI:0.936-1.000, p=0.047)と治療効果との関連を認めた。化学療法の有無と治療効果との関連は認めなかった。【結論】高度進行癌患者を中心とした今回の解析では、CD3-LAK療法が治療効果の発現に寄与していることが示唆された。末梢血リンパ球比率はCD3-LAK療法の治療効果に関連する因子であり、治療効果予測に有用である可能性が示された。

  112. 進行癌に対するCD3-LAK療法の治療効果関連因子についての検討

    岩城諒士、藤中沙奈恵、山田登美子、石川哲也、吉田松年

    第24回日本バイオセラピィ学会  2011.12.1  日本バイオセラピィ学会

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    Event date: 2011.12

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:和歌山   Country:Japan  

  113. CD3-LAK療法が進行癌患者のQOLに与える影響についての検討

    藤中沙奈恵、岩城諒士、山田登美子、石川哲也、吉田松年

    第24回日本バイオセラピィ学会  2011.12.1  日本バイオセラピィ学会

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    Event date: 2011.12

    Presentation type:Oral presentation (general)  

    Venue:和歌山   Country:Japan  

  114. CD3-LAK療法が進行癌患者のQOLに与える影響についての検討

    藤中沙奈恵,岩城諒士,山田登美子,石川哲也,吉田松年

    第24回日本バイオセラピィ学会 

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    Event date: 2011.12

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:和歌山   Country:Japan  

    【目的】近年、患者のQOLを考慮した癌治療が推奨されるようになり、QOLを温存する様々な工夫が報告されている。CD3-LAK療法などの免疫療法がQOLの維持、改善に寄与するという報告もあるが、正確なQOL評価に基づく報告は少ない。今回、我々はCD3-LAK療法が患者QOLに与える影響についての解析を行った。【対象・方法】2008年4月から2010年10月にCD3-LAK療法を施行された進行癌患者81例を対象とした。化学療法併用は51名、非併用は30名であった。CD3-LAK療法は2週間ごと、計6回を1クールとして施行した。1クール前後においてCT検査、血液・血清生化学検査、flow cytometerによる末梢血・培養液中の細胞分画検査、ELISAによる血清サイトカイン測定(TNF-, IL-6, VEGF, MIC-1)を行った。治療効果(腫瘍縮小効果)はCT画像よりRECIST基準に基づいて判定し、SD~PRの49例を治療効果あり群(あり群)、PDの32例を治療効果なし群(なし群)に分類した。QOL評価は、EORTC QLQ-C30質問表を用いて行った。統計解析はSPSS ver.11.0Jを用いた。【成績】EORTC QLQ-C30質問表の回答を点数化し、その平均値をとって治療前後の値を比較したところ、global QOLは治療後に改善していたが、呼吸困難は治療後に悪化していた。その他のQOL尺度は治療前後で有意な変化を認めなかった。治療効果の有無による比較では、個々のQOL尺度のうち身体機能、疲労感、嘔吐、疼痛、呼吸困難、不眠、食欲が、あり群で有意に改善していた。次に、各QOL尺度の改善・悪化に関与する因子について多変量解析(ロジスティック回帰分析)を行ったところ、VEGFの上昇が身体機能、疲労感の悪化に関連し、MIC-1の上昇が疲労感、疼痛、食欲不振、不眠の悪化に関連するなど、免疫関連因子がQOLを規定する因子として作用していることが示唆された。化学療法は、身体機能の悪化、嘔吐、疼痛の改善に関与していた。【結論】CD3-LAK療法は進行癌患者のQOL維持に有用である可能性が示された。また、QOL尺度のうち症状尺度の多くは治療効果による影響を受けること、個々のQOL尺度を規定する因子に免疫関連因子が比較的多く含まれることが示された。

  115. DDW-J2004薬物性肝障害診断基準案を用いた慢性腎臓病合併の有無による薬物性肝障害の検討

    綾田穣、堀田直樹、黒川剛、広瀬昭憲、増子和郎、石川哲也

    第47回日本肝臓学会総会 

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    Event date: 2011.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:東京   Country:Japan  

  116. ペグインターフェロン、リバビリン併用療法における凝固因子の検討

    本多隆、片野義明、林寛子、及部祐加子、小野幸矢、石津洋二、清水潤一、土居崎正雄、舘佳彦、林和彦、石上雅敏、中野功、石川哲也、後藤秀実

    第47回日本肝臓学会総会 

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    Event date: 2011.6

    Language:Japanese   Presentation type:Poster presentation  

    Venue:東京   Country:Japan  

  117. 活性化自己リンパ球療法は肺癌脳転移に対するガンマナイフ治療後の生存期間を延長させる -第二報-

    吉田松年, 石川哲也, 北野ゆかり, 山田登美子, 小林達也, 森美雅, 高橋宏, 鳥山高伸

    第23回日本バイオセラピィ学会学術集会総会 

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    Event date: 2010.12

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  118. 胸腔-静脈シャント(denver shunt)が有効だった、肝硬変由来の難治性右胸水の1例

    小野幸矢, 片野義明, 林寛子, 及部祐加子, 石津洋二, 清水潤一, 土居崎正雄, 舘佳彦, 本多隆, 林和彦, 石上雅敏, 中野功, 石川哲也, 後藤秀実

    第113回日本消化器病学会東海支部例会 

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    Event date: 2010.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  119. 透析患者のC型慢性肝炎に対するPEG-IFNa-2a単独投与の治療成績 International conference

    多賀雅浩, 竹田欽一, 宇都宮節夫, 川田登, 池田誉, 水谷佳貴, 広瀬健, 葛谷貞二, 石川哲也

    第14回日本肝臓学会大会 

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    Event date: 2010.10

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  120. インドールアミン酸素添加酵素による肝炎制御機構

    伊藤弘康, 石川哲也, 安藤量基, 森脇久隆, 清島満

    第46回日本肝臓学会総会 

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    Event date: 2010.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

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Research Project for Joint Research, Competitive Funding, etc. 7

  1. Development of a Novel Targeted Therapy for Chronic Hepatitis B to Regulate both Virus and Carcinogenesis

    Grant number:20fk0210077s0101, 21fk0210077s0102  2020.4 - 2023.3

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\6760000 ( Direct Cost: \5200000 、 Indirect Cost:\1560000 )

  2. イムノ・オミクス研究を基盤としたB型肝炎に対する治療法の開発

    Grant number:17fk0310106h0001, 18fk0310106h0002, 19fk0310106s0603, 20fk0310106s0604, 21fk0310106s0605  2017.4 - 2022.3

    肝炎等克服実用化研究事業 B型肝炎創薬実用化等研究事業  

    石川哲也

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\36950000 ( Direct Cost: \28423078 、 Indirect Cost:\8526922 )

  3. 獲得免疫反応の賦活化により核内HBV cccDNAを排除する手法の開発

    Grant number:17fk0310116h0001, 18fk0310116h0002, 19fk0310116s0103  2017.4 - 2020.3

    肝炎等克服実用化研究事業 B型肝炎創薬実用化等研究事業  

    石川哲也

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\5700000 ( Direct Cost: \4384617 、 Indirect Cost:\1315383 )

  4. iPS細胞分化・がん化の量子スイッチング in vivo Theranostics

    2013.8 - 2018.3

    再生医療実現拠点ネットワークプログラム 

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    Grant type:Competitive

    iPS細胞などの幹細胞に対して超低毒性な量子ドット、磁性ナノ粒子を創製し、これらをカプセル化する生体適合性材料開発により量子スイッチング能を有する新規量子・磁気ナノハイブリッド材料を創製することを目的とする。

  5. B型肝炎ウイルスの持続感染を再現する効率的な培養細胞 評価系の開発に関する研究

    2012.7 - 2017.3

    AMED-B型肝炎創薬実用化等研究事業 

    田中靖人

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    Grant type:Competitive

    HBV根絶を目指したB型肝炎創薬実用化研究を効率良く推進するために、HBV持続感染を再現する培養細胞評価系を開発し、HBV感染感受性・増殖機構から病態メカニズムの解明、レセプターの同定、薬剤スクリーニング等を効率的に実施できる簡便なシステムを構築する。

  6. HBV cccDNAの制御と排除を目指す新規免疫治療薬の開発

    2012.7 - 2017.3

    AMED-B型肝炎創薬実用化等研究事業 

    金子周一

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    Grant type:Competitive

    B型慢性肝炎の治療においては、肝炎ウイルスの増殖を低下させ、cccDNAを中心とするHBVの再活性化機構を制御することが重要である。本研究では、最先端の免疫学技術を用いて、cccDNAの制御と排除を行う新規治療薬の開発をめざす。

  7. 高齢者の食欲不振、低栄養状態の原因の解明に関する研究

    2011.4 - 2014.3

    長寿医療研究開発費 

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    Grant type:Competitive

    高齢者、特にパーキンソン病などの神経疾患を有する患者では、悪性疾患などの基礎疾患の合併がないにもかかわらず、食欲不振となり、その結果として体重減少、さらには低栄養状態といたる場合が少なくない。また、これらの患者においては、低栄養状態がなかなか改善しないことが原因で、しばしば低免疫状態となりを容易に肺炎などの感染症を併発したり、低栄養状態によるサルコペニアに進行していくと考えられる。
     この食欲不振に至る要因としては、加齢による消化管の運動機能の低下、消化管における吸収能の低下、食欲をつかさどる消化管ホルモンおよび免疫環境の変化などの関与が報告されてきた。しかしながら、いずれの要因が、高齢者の食欲不振、低栄養状態に関与しているかに関しては未だ完全に解明されてはおらず、改善策も乏しいのが現状である。
     本研究の目的は、消化管運動機能、消化管ホルモンや免疫機能、ピロリ菌感染の有無の面から検討して、高齢者の食欲不振、低栄養状態の一端を解明して、その対策(薬剤、生活習慣など)を立てることである。

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KAKENHI (Grants-in-Aid for Scientific Research) 17

  1. Establishment of a liver regeneration treatment model based on cell transplantation and development of a new treatment against immune rejection.

    Grant number:21K07959  2021.4 - 2024.3

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

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

  2. HBs抗原陰性化に関わるB型肝炎ウイルス変異と腸内細菌叢が及ぼす免疫応答の解明

    Grant number:20K08382  2020.4 - 2023.3

    日本学術振興会  科学研究費助成事業 基盤研究(C) 

    本多 隆

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\300000 ( Direct Cost: \300000 )

    B型肝炎ウイルス(HBV)排除は現在困難でありHBs抗原が陰性化する機能的治癒(Functional Cure: FC)が治療目標となる。一方自然経過でFCが得られる症例も存在するが、FCに関与する因子と詳しいメカニズムは不明である。申請者はHBVコアI97の変異症例では肝炎沈静化及びFC率が高いことを見出しているが、コア変異が起こる機序は不明である。本研究ではB型肝炎の肝炎沈静化及びFCに関連する因子について、コア変異を含むウイルス変異、免疫応答、腸内細菌叢、miRNAの解析を含め、多面的に調べることにより、コア変異と免疫応答の関係、腸内細菌叢を介した免疫応答とFCの関連などを明らかにする。

  3. 新規HBV感染症モデルを用いた治療的ワクチン療法の開発

    Grant number:19K08440  2019.4 - 2022.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    伊藤 弘康, 石川 哲也

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    HBV感染症は、急性肝炎・慢性肝炎・肝硬変・肝臓がんと進行性の肝疾患の原因となる。したがって、早期のHBV排除が必要となるが、現在HBVを完全に排除する治療法は確立されていない。申請者らは新規HBVマウスモデルの作製(基盤研究(C)2016.4~2019.3)を行っており、本モデルマウスを使用することにより、従来までの小動物HBV感染モデルでは困難であった宿主免疫応答の解析が可能となり治療的ワクチン療法の評価ができる。本研究では、最近開発された強力なアジュバンド効果を有するCpG-SPGを主に使用し、免疫チェックポイント阻害剤との併用を考慮しながら、新規治療的ワクチン療法の開発を行う。
    本年度は、1)新規HBV感染モデルマウスを用いて、HBs抗原およびcGAMPによる治療的ワクチン療法の効果についての検証、2)HVBトランスジェニック(HBVTg)マウスを用いて、治療的ワクチン療法におけるポリアミンの効果の検証 以上の2つの課題について主に検討した。新規HBV感染モデルマウスおよびHBVTgマウスともに治療的ワクチン(HBs抗原及びK3SPGまたはcGAMPによるワクチン療法)により液性免疫および細胞性免疫の増強がみられた。しかしながら、野生型マウスの比べまだ免疫能の十分な誘導は難しいと考えられた。ポリアミンの1種であるスペルミジンのアジュバンド効果増強作用の検証を行った。HBVTgマウスのみの準備実験の検討ではあるが、スペルミジンの投与がK3SPGやcGAMPのアジュバンド効果を増強させうることが示唆された。
    本年度は、申請者の異動のため新規マウスモデルの作製が十分であったとはいえない状況であった。しかしながら、以下の実験は遂行することができた。
    1)新規HBV感染マウスモデルに対して、HBs抗原とcGAMPによるワクチン療法を行い液性免疫および細胞性免疫の評価を行った。液性免疫能の評価のため血清中のHBs抗体を測定した。モデルマウスにてもHBs抗原とcGAMPによるワクチン療法により血清HBs抗体は増加したが、その増加は野生型マウスに比べ軽微であった。細胞性免疫に関しては脾細胞を用いたHBV関連抗原に対するIFN-γ産生能にて解析を行った。モデルマウスでは約50%マウスで抗原特異的IFN-γ産生がみられた。
    2)HVBトランスジェニック(HBVTg)マウスを用いて、治療的ワクチン療法におけるポリアミンの効果を予備実験として検討した。HBs抗原とアジュバンドとしてK3SPGまたはcGAMPにてワクチン療法をHBVTgマウスで行った。同時にポリアミンの1種であるスペルミジンを経口投与し、液性免疫と細胞性免疫の評価を行った。スペルミジンの投与はHBVTgマウスにおいて、K3SPGまたはcGAMPのアジュバンド投与時に液性免疫並びに細胞性免疫の増強を促進した。
    本年度は、研究代表者の異動により新規HBV感染モデルマウスでの検討が十分だったとは言い難い。本年度行った予備実験により、スペルミジンがK3SPGやcGAMPのアジュバンド効果を増強させることが示唆されるため、スペルミジンを加えた治療的ワクチン療法の効果について新規HBV感染モデルマウスにて検証を行う。現在、新規HBV感染モデルマウスが安定的に作製できるように環境を整備しつつあるが、安定的にモデルマウスが供給できないときのことも考えて、HBVTgマウスでの治療的ワクチン療法の検討も行っていく予定である。

  4. Monitoring of transplanted hepatocytes and analysis of immune rejection responses in the hepatocyte chimeric mouse system.

    Grant number:16K09354  2016.4 - 2019.3

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

    Ishikawa Tetsuya, YUKAWA Hiroshi, MATSUNAGA Tamihide, SUEMIZU Hiroshi, HAYASHI Yumi

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    Hepatocyte-chimera mouse system was established as a model for the cell transplantation treatment with hepatocytes or stem cell-derived cells. In the transgenic mice, HSVtk that express the thymidine kinase of human herpes simplex virus in their hepatocytes, administration of ganciclovir (GCV) kills autologous hepatocytes, enabling transplantation of hepatocytes of other origin. In the case of allogenic hepatocyte transplantation into HSVtk, all the transplanted cells were eliminated by a strong immune-rejection response. In the case of syngeneic hepatocytes expressing foreign antigens, efficient engraftment of transplanted cells was observed, while inflammatory cells infiltration around the engrafted cells and cellular immune response to the foreign antigens were confirmed. The hepatocyte-chimeric mouse system can be a useful model for elucidating the mechanism of immune rejection in the cell transplantation in the liver and for studying a therapeutic method for immune rejection.

  5. Development of an HBV infection mouse model using HSV-TK-WT mouse

    Grant number:16K09351  2016.4 - 2019.3

    Ito Hiroyasu

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Hepatitis B virus (HBV) is noncytopathic DNA virus with a circular, double-stranded genome. More than 350 million people are infected as chronic carriers and are at risk of developing end-stage hepatocellular carcinoma. The chronicity of HBV infection is involved in impaired HBV-specific immune responses that cannot eliminate or cure the infected hepatocytes efficiently. Treatment for HBV infection is difficult. The cause is that the HBV infected mouse model using small animals has not been established. In this study, HSV-TK-WT mice were intraperitoneally with ganciclovir (GCV) and transplanted with hepatocytes of HBV-Tg mice. HBsAg positive area in the liver tissue were observed for at least twenty weeks after HBV-Tg hepatocyte transplantation. IFN-γ producing cells increased in HSV-TK-WT mice with low HBsAg positive area in the liver tissue. The present mouse model will help to understand the mechanisms of HBV tolerance.

  6. In vivo imaging of transplanted stem cells by OTN-NIR fluorescence quantum dots

    Grant number:26790006  2014.4 - 2018.3

    Yukawa Hiroshi

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    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid) 

    Nobel Cd free quantum dots (QDs) which emit 1,000 nm wavelength fluorescence at infrared region with high compatibility were synthesized, and optical properties (fluorescence intensity, quantum yield, life time, and stability) of the QDs were checked. In addition, the transduction efficiency and cytotoxicity of the QDs to stem cells were investigated, and the self-proliferation and multipotency of stem cells labeled with QDs were checked. Moreover, in vivo fluorescence imaging of transplanted stem cells labeled with QDs were addressed and was found to be useful for the assessment of acute liver failure mice.

  7. 免疫学的劇症肝炎モデルマウスにおける新たな細胞治療の基礎的検討

    2012.4 - 2015.3

    科学研究費補助金  基盤研究(C)

    石上雅敏

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    劇症肝炎を始めとする急性肝不全は、治療法の発達した現在でも約半数が不幸な転帰を取る難治性疾患である。本疾患治療の根本的な鍵である肝再生への日常臨床に適用可能な介入方法は未だ確立されていない。本研究では、本邦における劇症肝炎の主要な原因である免疫の関与が考えられる肝炎モデルマウスに対し、新たな細胞治療を用いることで、その発症から肝再生による治癒に至るまでの過程においていかなるメカニズムが働くのかを明らかにし、今後の治療応用への基礎的検討を行う。

  8. 炎症・ウイルス感染環境下での肝構成細胞の免疫・代謝応答の解析

    2011.4 - 2014.3

    科学研究費補助金  基盤研究(C)

    石川哲也

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    Authorship:Principal investigator 

    本研究は、肝細胞を始めとする肝構成細胞が炎症・免疫応答にどのように反応し、その後の炎症・免疫、代謝などの生体応答にどのような影響を与えるかを解析するために計画した。
    肝構成細胞をin vitro での炎症刺激による擬似肝炎環境下におき、それぞれにおけるケモカイン/サイトカイン、自然免疫関連分子群、細胞内蛋白・脂質代謝への影響をそれぞれ解析する。また、B型・C型肝炎ウイルス蛋白を発現する肝細胞を用いて同様の解析を行い、ウイルス感染による炎症・免疫、代謝応答の修飾を解析する。これまで個体レベルで総和としてみていた肝炎という現象を、細胞レベルで詳細に解析することを目的とする。

  9. Analysis of immune and metabolic responses of liver cells under inflammatory circumstances or viral infection

    Grant number:23590970  2011 - 2013

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

    ISHIKAWA TETSUYA, ISHIGAMI Masatoshi, UEYAMA Jun

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    Authorship:Principal investigator 

    Grant amount:\5200000 ( Direct Cost: \4000000 、 Indirect Cost:\1200000 )

    To elucidate the role of hepatic parencymal cells on the pathogenesis of hepatitis, the expression patterns of cytokines and chemokines by hepatoma cell lines under inflammatory circumstance were analyzed. In three hepatoma cell lines used, the expressions of inflammatory cytokines and chemokies were up-regulated after various inflammatory stimuli. The pathogenetic importance of hepatic parencymal cells in the formation of hepatic inflammation is confirmed, and in vitro hepatitis model used in the current study is thought to be useful for the detailed analysis of the pathogenesis of hepatitis.

  10. Investigation of novel therapeutic approach through regulatory T cells (Tr) and dendritic cells (DCs) for the patients with autoimmune hepatitis (AIH)

    Grant number:18590754  2006 - 2007

    OKUMURA Akihiko

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    Authorship:Coinvestigator(s) 

    (1) Expression of toll-like receptor (TLR) family on Dendritic cells (DCs) in patients with autoimmune hepatitis (AIH). Total RNA was extracted from isolated T-reg and non-T-reg fractions and the amount of mRNA for TLR2, 3, 4, 6, 7, 8, 9were evaluated by real time PCR. TLR3, 6, 7, 9were expressed on circulating myeloid DC (MDC) and plasmacytoid DC (PDC) in controls, while only TLR6was expressed on those in patients with AIH. Thus different expression pattern of TLRs on DCs might have some influence on the pathogenesis of AIH.
    (2) Expression of apoptosis-related molecules on DCs, and susceptibility of DCs to apoptosis induced through TNF-R1 in patients with AIH.
    Total RNA was extracted from circulating myeloid DC (MDC) and plasmacytoid DC (PDC), the amount of mRNA for TNF-R1, TNF-RS18, Fas, Bcl-2, Bax, Bad, FAST, PKR, Apaf-1, and c-FLIP were evaluated by real time PCR. Further, after incubation of MDC+PDC in the presence of TNFα, susceptibility to apoptosis induced through TNF-R1 was evaluated by counting the number of apoptotic DCs. TNF-RS18, TNF-R1, Bad, and FAST were expressed on freshly isolated MDC and PDC both in AIH and control. However, expression of TNF-R1 and Bad was significantly suppressed in AIH compared with controls. After 72 hour incubation in the presence of TNFα, the amount of apoptotic MDC and PDC in controls increased from 30.0% to 45.8%, whereas that in AIH changed from 33.3% to 34.5%, suggesting the possibility that apoptosis of MDC and PDC induced by signals through TNF-R1 is suppressed in AIH.

  11. Analysis and therapeutic application of crosstalk between innate immunity and acquired immunity in viral hepatitis.

    Grant number:17590688  2005 - 2006

    ISHIKAWA Tetsuya

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    Authorship:Principal investigator 

    Grant amount:\3600000 ( Direct Cost: \3600000 )

    Natural killer T (NKT) cells are one of the major cell populations in the liver and thought to play important roles on immune-pathogenesis of hepatitis. On the other hand, cytotoxic T lymphocytes (CTLs) are thought to be major effectors for clearing viruses in acute infections including hepatitis B virus(HBV). Persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which is thought to reflect tolerance to HBV antigens. In the present study, we found that alpha-galactosylceramide (α-GalCer), a ligand for Vα14-positive NKT cells stropgly enhanced the induction and proliferation of HBV-specific CTLs by HBsAg. In HBsAg transgenic mice, which are thought to be tolerant to HBV-encoded antigens, administration of HBsAg or α-GalCer alone failed to induce HBsAg-specific CTLs, but co-administration of the both compounds did induce them. A blocking experiment using antibodies to cytokines and CD40 ligand showed that IL-2 and CD40/CD4OL interaction mediate the enhancement of CTL induction caused by α-GalCer through NKT cell activation. The crosstalk between innate and acquired immunity could be applied to the intractable infectious diseases like HBV infection.

  12. Roles of regulatory T cells (Tr) and dendritic cells (DCs) in the pathogenesis of autoimmune hepatitis(AIH)

    Grant number:16590644  2004 - 2005

    OKUMURA Akihiko

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    (1) Impaired regulatory T cell functions in patients with autoimmune hepatitis
    The importance of CD4^+CD25^+regulatory T cell (Tr)-mediated control of self-reactive T cells has been focused on. Recently, several molecules including Foxp3, CTLA4, and GITR (TNFRSF18) were identified as key molecules which control the development and activation of T-reg. We investigated whether there were any difference in the expression pattern of these key molecules on T-reg, and whether there were any difference in the function of T-reg in the patients with type 1 autoimmune hepatitis (AIH). The proportion of T-reg was increased in AIH compared with controls. mRNA for Foxp3 and Ctla4, both molecules are known to activate the function of T-reg, were significantly decreased in AIH compared with controls. We tested if the function of T-reg in AIR was impaired or not after stimulation by OKT3. Although no obvious difference in induction of TNF-α, IFN-γ, and TGF-β was identified, production of IL-10 was significantly lower in AIH than in controls. Our results implies the possibility that genetical difference in the expression of Foxp3 and/or CTLA4 on T-reg might lead to the impaired function of T-reg, and finally to the breakthrough of peripheral tolerance in AIH.
    (2) Expression of toll-like receptor (TLR) family on regulatory T cells in patients with autoimmune hepatitis
    It has been shown that naturally arising T-reg selectively express several members of the TLR family, and that signals through TLRs modulate the function of T-regs. We investigated the expression pattern of TLRs on T-reg in the patients with AIH. Total RNA was extracted from isolated T-reg and non-T-reg fractions and the amount of mRNA for TLR2, 3, 4, 6, 7, 8, 9 were evaluated by real time PCR. In AIH, as well as controls, TLR3, 4, 6, 7, 9 were expressed on Tr. Our results implies the possibility that the signals through TLRs expressed on T-reg might regulate the function of T-reg in AIH. Next we investigated the expression pattern of TLRs on dendritic cells (DCs) in the same manner. Myeloid derived DCs (MDDC) in the peripheral blood of patients with AIH expressed only TLR 6 whereas those of healthy controls expressed TLR 3, 4, 6, 7, 9. Thus Tr might regulated by the signal through the molecules like Foxp3, CTLA-4, and TLR. Further, different expression pattern of TLR on MDDC in AIH might have some influence on functional regulation of Tr by DCs.

  13. Identification and clinical application for the role of NKT cells in patients with chronic hepatitis and hepatocellualr carcinoma infected hepatitis virus

    Grant number:15390236  2003 - 2005

    KAKUMU Shinichi

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    Natural killer T (NKT) cells share features of both classical T cells and NK cells. NKT cells are heterogenous populations, and recognize glycolipids associated with CD1d molecule. We investigated Th1/Th2 cytokine production as well as frequency and phenotype of circulating NKT cells in patients with chronic hepatitis (CH) and hepatocellular carcinoma (HCC) infected with hepatitis C virus (HCV). Peripheral blood mononuclear cells (PBMC) were obtained befor and 2 weeks later IFN/ribavirin and radiofrequency ablation therapy for CH and HCC, respectively. PBMC were cultured with α galactosylceramide (α GalCer) and IL-2. Frequency and cytokine production of NKT cells were analyzed with flow cytometry. IFN-γ production of Vα 24+CD3+ T cells did not differ among groups, but became greater after treatment in contrast to lowered IL-4 production.
    The function of dendritic cells (DCs) appears to be decreased in patients with chronic hepatitis C. However, we have no strategy to modulate its function. Thus we wanted to induce maturated DC by activating V α 24+ NKT cells. We cultured peripheral blood CD14+ cells in the presence of GMCSF and IL-4. Simultaneously CD3+ T cells were cultured with α GalCer + IL-2. After 5-day culture, they are mixed and cultured with GMCSF, α GalCer and IL-2 for further 2 days. This method induced matured, functional DC.
    Cytotoxic T lymphocyes (CTLs) are thought to be major effectors for clearing viruses in acute infections including hepatitis B virus (HBV). Persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which is thought to reflect tolerance to HBV antigens. We found that α GalCer, a ligand for V α 14+ NKT cells in mice, strongly enhanced the induction and proliferation of HBV-specific CTLs by HBsAg. In HbsAg transgenic mice, which are thought to be tolerant to HBV-encoded antigens, administration of HbsAg or α GalCer alone failed to HbsAg-specific CTLs, but they were induced by administration of both compounds. A blocking experiment using antibodies to cytokines and CD4O ligand showed that IL-2 mediates the enhancement of CTL induction caused by α GalCer through NKT activation.

  14. Analysis for the kinetics of host gene expression in the progression or recovery process of hepatic inflammation.

    Grant number:15590697  2003 - 2004

    ISHIKAWA Tetsuya

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    Authorship:Principal investigator 

    Grant amount:\3600000 ( Direct Cost: \3600000 )

    Adoptive transfer of HBs-specific CTL clones into HBV-transgenic mice (HBV-Tg) causes acute or fluminant hepatitis in those mice. Using this model, we investigated the mechanism and the pathogenesis of immune-mediated hepatitis. The magnitude of hepatitis differed and sometimes showed more than ten times difference depending on the CTL clones used for the transfer. The differences in the disease by the individual CTL clones did not depend on the amount of the cytokines, such as TNF-α and IFN-γ, produced by the CTL clones. The disease magnitude might be determined by other functions of CTL clone, the extent of host effector cell activation, or unknown host factors affected by the CTL administration. To explore these possibilities, we established HBV-Tg with TNF-α gene knockout (HBV-Tg/TNF-α KO), and HBV-Tg with Jα281 gene knockout (HBV-Tg/NKT KO), and analyzed the roles of TNF-α and NKT cells for the disease pathogenesis. The disease magnitude dramatically declined in HBV-Tg/TNF-α KO compared to that in HBV-Tg, showing the decrease of peak transaminase levels less than one twentieth of those in HBV-Tg. The cell population responsible for TNF-α production, the factors that regulate TNF-α, and influence of TNF-α for the expression of other host genes, are currently under investigation. On the other hand, the peak transaminase levels were significantly raised in HBV-Tg/NKT KO compared to those in HBV-Tg. The expression of IL-10 was upregulated in hepatic NKT cells of HBV-Tg as early as 3 hours after CTL administration. These results may suggest that NKT cells suppress the expressive exacerbation of hepatitis through IL-10 production. Various immune cells as well as cytokine play multilateral roles on disease pathogenesis of hepatitis. The detailed analyses for these players are necessary to explore the possibilities of novel therapy for hepatitis, which aims the specific reduction of inflammation and the promotion of liver regeneration.

  15. Establishment of murine model for auto immune hepatitis (AIH)

    Grant number:14570523  2002 - 2003

    OKUMURA Akihiko

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    Background : We established murine hepatitis model by immunizing mice with human P450IID6 (CYP2D6), the target molecule of LKM-1 antibody. In the present study, we investigated the mechanism of liver cell injury in AIH, including the dynamics of T-reg, using our murine hepatitis model. Materials and methods : Eight week old C57BL/6 male mice were immunized with β-gal-CYP2D6 (0.1μmol), the fusion protein of β-gal and CYP2D6, intraperitoneally. Serum levels of ALT and anti-CYP2D6, and histologic changes in the liver were tested weekly until 4 week after immunization. To determine the proportion of CD4^+-T cell, CD8^+-T cell, and T-reg, liver infiltrating lymphocytes (LIL) and splenocytes (SP) were collected, stained with anti-CD4-PE in combination with anti-CD8-FITC or anti-CD25-FITC, and run on FACS flow cytometer, collecting data on 1x10^4 cells, analyzed using Cell Quest software. Results : Serum ALT level reached the peak at 2 week after immunization and returned to normal level at 4 week in the mice immunized with β-gal-CYP2D6. Histologically, periportal infiltration of the inflammatory cells and focal necrosis in the lobule was observed in the livers of the β-gal-CYP2D6-immunized mice. When LIL were used for the FACS analysis, the ratio of CD4/CD8 decreased at 1 week after immunization, synchronized with the elevation of ALT levels, then recovered gradually in parallel with the resolution of ALT flare. When SP were used, however, the change of CD4/CD8 was marginal, indicating the different dynamics of CD4^+- and CD8^+-T cells in SP from that in LIL during the course of hepatitis. The frequency of CD4^+ CD25^+-T cell (T-reg) in SP were similar to LIL. The frequency of T-reg in LIL decreased immediately at 1 week after immunization, and gradually increased to the same level as pre-immunization. T-reg in SP decreased more slowly than that in LIL, reached minimum at 2 week after immunization, then increased similarly to T-reg in LIL. Conclusions : Immunization of C57BL/6 mice with β-gal-CYP2D6 resulted in inflammation in the liver. Our results using FACS analysis indicated the predominance of CD8^+T cells in the livers with hepatitis. Further, the frequency of T-reg changed drastically during the flare of ALT levels, implies the possibility that T-reg play some roles on the course of hepatitis.

  16. To clarify the mechanism of chronicity and to explore therapeutic approach for viral hepatitis

    Grant number:12670529  2000 - 2001

    KAKUMU Shinichi

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    Authorship:Principal investigator 

    Grant amount:\3400000 ( Direct Cost: \3400000 )

    The mechanism of chtonicity in viral hepatitis is not well understood until present. Since hepatitis B virus (HBV) and hepatitis C virus (HCV) are not cytopathic, hepatic injury in HBV and HCV infection is thought to be caused by the attack of host immune responses against virus-infected hepatocytes. And it is vaguely thought that the weakness of the immune responses against viral proteins is responsible for the chronicity of viral hepatitis. To elucidate the mechanism of the chronicity, the functions of the cytotoxic T lymphocyte (CIL), one of the main effectors of host immune responses is studied in vitro. The functions of CIL, both proliferative activity and the killing activity were greatly impaired after antigen stimulation without the existence of costimulatory signals. This implies that the hepatocytes lacking the expression of costimulatory molecules may inactivate the CILs after contact and that it may be one of the main mechanisms for the persistence of hepatitis viruses. HBV-transgenic mice (Tg) are the models for HBV carriers in human. Immunization of HBV-Tg with HBs-cDNA results in the downregulation of the virus to some extent, however, the occurrence of complete clearance of viral products is very rare. To increase the efficacy of viral downregulation , cDNAs of HBs and costimulatory molecules (B7 1, B7-2, or CD40) were simultaneously used to immunize HBV-Tg. Although co-immunization with both molecules did not increase the ratio of complete viral downregulation in HBV-Tg, it resulted in the manifestation of hepatitis that was not observed in the immunization of HBs-cDNA alone. This suggests that the efficacy of inducing HBV-specific immune response is improved by the co-immunization. Simultaneous use of costimulatory molecules for immunization may be the clue for the thrapeutic approach to treat chronic infection of hepatitis viruses.

  17. Pathologicl significance and its inhibition of apoptosis on the development and its progression of liver injury.

    Grant number:10470142  1998 - 2000

    KAKUMU Shinichi

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    Toxic effects of chloramphenicol, an antibiotic inhibitor of mitochondrial protein synthesis, on rat liver derived RL-34 cell line were completely blocked by a combined treatment with substances endowed with direct or indirect antioxidant properties. A stable, nitroxide free radical scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, and a protein synthesis inhibitor, cycloheximide, suppressed in a similar manner the following manifestations of the chloramphenicol cytotoxicity : (1) Oxidative stress state as evidenced by FACS analysis of cells loaded with carboxy-dichlorodihydrofluorescein diacetate and Mito Tracker CMTH_2MRos ; (2) megamitochondoria formation detected by staining of mitochondria with Mito Tracker CMXRos under a laser confocal microscopy and electron microscopy ; (3) apoptotic changes of the cell detected by the phase contrast microscopy, DNA laddering analysis and cell cycle analysis. Since increases of ROS generation in chloramphenicol-treated cells were the first sign of the chloramphenicol toxicity, we assume that oxidative stress state is a mediator of above described alternations of RL-34 cells including MG formation. Pretreatment of cells with cycloheximide or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, which is known to be localized into mitochondria, inhibited the megamitochondria formation and succeeding apoptotic changes of the cell. Protective effects of cycloheximide, which enhances the expression of Bcl-2 protein, may further confirm our hypothesis that the megamitochondria formation is a cellular response to an increased ROS generation and raise a possibility that antiapoptotic action of the drug is exerted via the protection of the mitochondria functions.

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Teaching Experience (On-campus) 36

  1. Pharmacology

    2021

  2. Immunology

    2021

  3. Medical Electronics

    2021

  4. Molecular Pathophysiology

    2021

  5. Medical English IB

    2021

  6. Laboratory Molecular Genetics

    2021

  7. Biochemistry B

    2021

  8. Introduction to Food Function and Safety

    2021

  9. Biochemistry A

    2021

  10. Research Work

    2021

  11. Special Lectures on Biomolecular Sciences

    2021

  12. Research Work

    2021

  13. Practicum on Omics Health Sciences II

    2021

  14. Introduction to Pathophysiology

    2021

  15. Basic Training

    2021

  16. Laboratory Analysis Practice B

    2021

  17. Laboratory Analysis II Medical Safety and Management

    2021

  18. 臨床病理学演習

    2021

  19. 生物学実験

    2021

  20. Clinical Medicine I

    2021

  21. Medical Technology Special Lecture III

    2021

  22. Laboratory Analysis Practice A

    2021

  23. General Clinical Pathology I

    2021

  24. 生物学基礎Ⅱ

    2021

  25. Clinical Medicine III

    2021

  26. Medical English IIB

    2021

  27. Specialized Studies on Biomolecular Sciences

    2021

  28. Clinical Medicine II

    2021

  29. 一般検査学

    2012

  30. 保健生化学B

    2012

  31. 臨床病理学Ⅰ

    2012

  32. 保健生化学A

    2012

  33. 人体構造機能学ⅣA(生化学)

    2012

  34. 一般検査学実習B

    2012

  35. 一般検査学実習A

    2012

  36. First Year Seminar A

    2012

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