2021/04/08 更新

写真a

シラハ ヒデノリ
白羽 英則
SHIRAHA Hidenori
所属
岡山大学病院 講師
職名
講師
プロフィール
消化器癌の分子機構について研究をしています。
特にEMTや癌幹細胞化に興味を持っています。
また、消化器癌に対するREIC遺伝子治療も遂行しています。
外部リンク

研究キーワード

  • 消化器癌

  • 癌幹細胞

  • EMT

  • 肝がん

  • 遺伝子治療

研究分野

  • ライフサイエンス / 消化器内科学

学歴

  • 岡山大学   Graduate School of Medicine  

    1992年4月 - 1996年3月

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  • 岡山大学   医学部   医学科

    1986年4月 - 1992年3月

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経歴

  • 岡山大学   消化器内科   講師

    2011年4月 - 現在

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  • 岡山大学   医学部歯学部附属病院   助教

    2007年4月 - 2011年3月

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  • 岡山大学   医学部歯学部附属病院   助手

    2004年1月 - 2007年3月

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  • 岡山大学   機能再生再建科学   日本学術振興会特別研究員

    2002年4月 - 2003年12月

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  • ピッツバーグ大学   病理学教室   博士研究員

    1999年8月 - 2002年3月

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  • アラバマ州立大学バーミングハム校   病理学教室   博士研究員

    1997年4月 - 1999年7月

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  • 岡山大学   医学部 第一内科   研究生

    1996年4月 - 1997年3月

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▼全件表示

所属学協会

 

論文

  • Serum REIC/Dickkopf-3 Protein Level Predicts Disease-Free Survival in Patients with Hepatocellular Carcinoma. 査読

    Atsushi Oyama, Daisuke Uchida, Hidenori Shiraha, Hiroaki Sawahara, Ryo Kato, Masaya Iwamuro, Shigeru Horiguchi, Hiroyuki Okada

    Acta medica Okayama74 ( 3 ) 237 - 243   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The physiological role of the reduced expression of immortalized cells (REIC)/Dickkopf-3 (Dkk-3) protein in patients with hepatocellular carcinoma (HCC) remains unclear. In this study, we evaluated the effect of the REIC/Dkk-3 protein on HCC cell proliferation and assessed the relationship between the serum REIC/Dkk-3 protein level and the prognosis in patients with HCC. We evaluated the REIC/Dkk-3 protein-induced anticancer effects on Huh7 and Hep3B cells (HCC cell lines) in the presence of peripheral blood mononuclear cells (PBMCs), and found that combination treatment with REIC/Dkk-3 protein and PBMCs reduced the proliferation of HCC cells (Hep3B: 82.0%±16.3%; Huh7: 72.6%±9.1%). We also studied 194 HCC patients who underwent primary liver resection or primary radiofrequency ablation from 2008 to 2017. Serum REIC/Dkk-3 protein levels were measured by an enzyme-linked immunosorbent assay and compared to the prognostic data. The 3-year disease-free survival of the REIC/Dkk-3 high group was significantly higher than that in the REIC/Dkk-3 low group. In conclusion, this is the first study investigating the relationship between HCC patient survival and serum REIC/Dkk-3 protein levels in a large population. Based on the results, the serum REIC/Dkk-3 protein level should be considered a new prognostic marker for patients with HCC.

    DOI: 10.18926/AMO/59957

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  • Promising Gene Therapy Using an Adenovirus Vector Carrying REIC/Dkk-3 Gene for the Treatment of Biliary Cancer. 査読 国際誌

    Emi Tanaka, Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Atsushi Ohyama, Masaya Iwamuro, Masami Watanabe, Hiromi Kumon, Hiroyuki Okada

    Current gene therapy20 ( 1 ) 64 - 70   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: We previously demonstrated that the reduced expression in immortalized cells (REIC)/dikkopf-3 (Dkk-3) gene was downregulated in various malignant tumors, and that an adenovirus vector carrying the REIC/Dkk-3 gene, termed Ad-REIC induced cancer-selective apoptosis in pancreatic cancer and hepatocellular carcinoma. OBJECTIVE: In this study, we examined the therapeutic effects of Ad-REIC in biliary cancer using a second- generation Ad-REIC (Ad-SGE-REIC). METHODS: Human biliary cancer cell lines (G-415, TFK-1) were used in this study. The cell viability and apoptotic effect of Ad-SGE-REIC were assessed in vitro using an MTT assay and Hoechst staining. The anti-tumor effect in vivo was assessed in a mouse xenograft model. We also assessed the therapeutic effects of Ad-SGE-REIC therapy with cisplatin. Cell signaling was assessed by Western blotting. RESULTS: Ad-SGE-REIC reduced cell viability, and induced apoptosis in biliary cancer cell lines via the activation of the c-Jun N-terminal kinase pathway. Ad-SGE-REIC also inhibited tumor growth in a mouse xenograft model. This effect was further enhanced in combination with cisplatin. CONCLUSION: Ad-SGE-REIC induced apoptosis and inhibited tumor growth in biliary cancer cells. REIC/Dkk-3 gene therapy using Ad-SGE-REIC is an attractive therapeutic tool for biliary cancer.

    DOI: 10.2174/1566523220666200309125709

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  • A Phase I/Ib trial of Ad-REIC in liver cancer: study protocol. 査読

    Oyama A, Shiraha H, Uchida D, Iwamuro M, Kato H, Takaki A, Ikeda F, Onishi H, Yasunaka T, Takeuchi Y, Wada N, Iwasaki Y, Sakata M, Okada H, Kumon H

    Future oncology (London, England)15 ( 31 ) 3547 - 3554   2019年11月

  • The Efficacy and Safety of Steroids for Preventing Postembolization Syndrome after Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma. 査読

    Kuwaki K, Nouso K, Miyashita M, Makino Y, Hagihara H, Moriya A, Adachi T, Wada N, Yasunaka Y, Yasunaka T, Takeuchi Y, Onishi H, Nakamura S, Ikeda F, Shiraha H, Takaki A, Okada H

    Acta medica Okayama73 ( 4 ) 333 - 339   2019年8月

  • Monitoring serum proangiogenic cytokines from hepatocellular carcinoma patients treated with sorafenib. 査読

    Adachi T, Nouso K, Miyahara K, Oyama A, Wada N, Dohi C, Takeuchi Y, Yasunaka T, Onishi H, Ikeda F, Nakamura S, Shiraha H, Takaki A, Takabatake H, Fujioka SI, Kobashi H, Takuma Y, Iwadou S, Uematsu S, Takaguchi K, Hagihara H, Okada H, Okayama Liver, Cancer Group

    Journal of gastroenterology and hepatology34 ( 6 ) 1081 - 1087   2019年6月

  • A Huge Liver Cyst Manifesting Dyspnea and Edema. 査読

    Nagao S, Iwamuro M, Shiraha H, Otsuka F

    Internal medicine (Tokyo, Japan)58 ( 12 ) 1811 - 1812   2019年6月

  • Predictive Factors for Successful Vaccination Against Hepatitis B Surface Antigen in Patients Who Have Undergone Orthotopic Liver Transplantation. 査読

    Ikeda A, Takaki A, Yasunaka T, Oyama A, Adachi T, Wada N, Onishi H, Ikeda F, Shiraha H, Yoshida K, Kuise T, Nobuoka D, Yoshida R, Umeda Y, Yagi T, Fujiwara T, Okada H

    Acta medica Okayama73 ( 1 ) 41 - 50   2019年2月

  • [Adefovir Dipivoxil-induced Fanconi's Syndrome and Osteomalacia Following Multiple Bone Fractures in a Patient with Chronic Hepatitis B]. 査読

    Makita T, Kanzaki H, Onishi H, Ikeda A, Takaki A, Wada N, Takeuchi Y, Yasunaka T, Ikeda F, Shiraha H, Tanaka Y, Nishihara S, Murakawa K, Kitamura Y, Okada H, Sendo T

    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan139 ( 4 ) 641 - 645   2019年

  • Dipeptide γ-secretase inhibitor treatment enhances the anti-tumor effects of cisplatin against gastric cancer by suppressing cancer stem cell properties. 査読 国際誌

    Kato R, Iwamuro M, Shiraha H, Horiguchi S, Tanaka E, Matsumoto K, Ohyama A, Sawahara H, Nagahara T, Uchida D, Tsutsumi K, Okada H

    Oncology letters16 ( 4 ) 5426 - 5432   2018年10月

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    記述言語:英語  

    DOI: 10.3892/ol.2018.9301

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  • All carbonated beverages effectively dissolve phytobezoars. 査読

    Iwamuro M, Yamauchi K, Shiraha H, Okada H

    Clinics and research in hepatology and gastroenterology42 ( 4 ) e66 - e67   2018年9月

  • A subclinical high tricuspid regurgitation pressure gradient independent of the mean pulmonary artery pressure is a risk factor for the survival after living donor liver transplantation 査読

    Yosuke Saragai, Akinobu Takaki, Yuzo Umeda, Takashi Matsusaki, Tetsuya Yasunaka, Atsushi Oyama, Ryuji Kaku, Kazufumi Nakamura, Ryuichi Yoshida, Daisuke Nobuoka, Takashi Kuise, Kosei Takagi, Takuya Adachi, Nozomu Wada, Yasuto Takeuchi, Kazuko Koike, Fusao Ikeda, Hideki Onishi, Hidenori Shiraha, Shinichiro Nakamura, Hiroshi Morimatsu, Hiroshi Ito, Toshiyoshi Fujiwara, Takahito Yagi, Hiroyuki Okada

    BMC Gastroenterology18 ( 1 ) 62   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BioMed Central Ltd.  

    Background: Portopulmonary hypertension (POPH) is characterized by pulmonary vasoconstriction, while hepatopulmonary syndrome (HPS) is characterized by vasodilation. Definite POPH is a risk factor for the survival after orthotopic liver transplantation (OLT), as the congestive pressure affects the grafted liver, while subclinical pulmonary hypertension (PH) has been acknowledged as a non-risk factor for deceased donor OLT. Given that PH measurement requires cardiac catheterization, the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography is used to screen for PH and congestive pressure to the liver. We investigated the impact of a subclinical high TRPG on the survival of small grafted living donor liver transplantation (LDLT). Methods: We retrospectively analyzed 84 LDLT candidates. Patients exhibiting a TRPG ≥25 mmHg on echocardiography were categorized as potentially having liver congestion (subclinical high TRPG
    n=34). The mean pulmonary artery pressure (mPAP) measured after general anesthesia with FIO20.6 (mPAP-FIO20.6) was also assessed. Patients exhibiting pO2&lt
    80 mmHg and an alveolar-arterial oxygen gradient (AaDO2)≥15 mmHg were categorized as potentially having HPS (subclinical HPS
    n=29). The clinical course after LDLT was investigated according to subclinical high TRPG. Results: A subclinical high TRPG (p=0.012) and older donor age (p=0.008) were correlated with a poor 40-month survival. Although a higher mPAP-FIO20.6 was expected to correlate with a worse survival, a high mPAP-FIO20.6 with a low TRPG was associated with high frequency complicating subclinical HPS and a good survival, suggesting a reduction in the PH pressure via pulmonary shunt. Conclusion: In cirrhosis patients, mPAP-FIO20.6 may not accurately reflect the congestive pressure to the liver, as the pressure might escape via pulmonary shunt. A subclinical high TRPG is an important marker for predicting a worse survival after LDLT, possibly reflecting congestive pressure to the grafted small liver.

    DOI: 10.1186/s12876-018-0793-z

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  • Transcatheter Arterial Chemoembolization to Reduce Size of Hepatocellular Carcinoma before Radiofrequency Ablation. 査読

    Ako S, Nakamura S, Nouso K, Dohi C, Wada N, Morimoto Y, Takeuchi Y, Yasunaka T, Kuwaki K, Onishi H, Ikeda F, Shiraha H, Takaki A, Okada H

    Acta medica Okayama72 ( 1 ) 47 - 52   2018年2月

  • Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf-3 expressing adenoviral vector for hepatocellular carcinoma 査読

    Hiroaki Sawahara, Hidenori Shiraha, Daisuke Uchida, Hironari Kato, Ryo Kato, Atsushi Oyama, Teruya Nagahara, Masaya Iwamuro, Shigeru Horiguchi, Koichiro Tsutsumi, Mari Mandai, Tetsushige Mimura, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Masami Watanabe, Masakiyo Sakaguchi, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Okada

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY32 ( 10 ) 1769 - 1777   2017年10月

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

    Background and Aim: Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed.
    Methods: Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice.
    Results: REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6).
    Conclusions: Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC.

    DOI: 10.1111/jgh.13757

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  • Dynamic computed tomography is useful for prediction of pathological grade in pancreatic neuroendocrine neoplasm 査読

    Shigeru Horiguchi, Hironari Kato, Hidenori Shiraha, Koichiro Tsutsumi, Naoki Yamamoto, Kazuyuki Matsumoto, Takeshi Tomoda, Daisuke Uchida, Yutaka Akimoto, Syou Mizukawa, Takehiro Tanaka, Koichi Ichimura, Akinobu Takaki, Takahito Yagi, Hiroyuki Okada

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY32 ( 4 ) 925 - 931   2017年4月

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

    Background and Aim Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS-FNA and dynamic CT in the diagnosis and pathological grading of PNEN.
    Methods In this retrospective study, 39 PNEN patients finally diagnosed via EUS-FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD.
    Results By using EUS-FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio (r=0.83, P<0.0001) and pathological grade (P=0.0074).
    Conclusions Computed tomography ratio has a relationship with pathological grade in PNEN, which would help decide therapeutic strategy in unresectable cases and cases in which pathological grading is difficult.

    DOI: 10.1111/jgh.13594

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  • Application of radiofrequency ablation for the treatment of intermediate-stage hepatocellular carcinoma 査読

    Kazuhiro Nouso, Kazuya Kariyama, Shinichiro Nakamura, Ayano Oonishi, Akiko Wakuta, Atsushi Oyama, Soichiro Ako, Chihiro Dohi, Nozomu Wada, Yuki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY32 ( 3 ) 695 - 700   2017年3月

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

    Background and Aim: Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate-stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate-stage HCC.
    Methods: Among 246 patients who were initially diagnosed with intermediate-stage HCC, 76 who were treated with TACE (TACE group) and 91 who were treated with RFA (RFA group) were enrolled in this study. The risk for survival was analyzed with the Cox Proportional Hazard Model, and the survival rates were compared using propensity score matching.
    Results: About half (50.6%) of the intermediate-stage HCC patients in the RFA group were diagnosed with Barcelona Clinic Liver Cancer substage-B1 (BCLC-B1) compared with only 19.7% of the patients in the TACE group. Survival of the RFA group was longer than that of TACE group in patients with BCLC-B1 and BCLC-B2. In contrast, no difference between groups was observed in patients with BCLC-B3/4. Multivariate analysis revealed that large tumor size (> 30 mm, hazard ratio = 1.685, P = 0.043), high des-gamma-carboxyprothrombin (> 100 mAU/mL, hazard ratio = 1.920, P = 0.012), and TACE group (hazard ratio = 1.896, P = 0.016) were significant risk factors for survival. Overall 3-year survival of the patients in the RFA group (69.5%) was significantly longer than that of patients in the TACE group (51.5%) after propensity score matching (P = 0.032). No significant adverse events were observed in either group.
    Conclusions: RFA was useful for the treatment of less advanced intermediate-stage HCC and could be an alternative to TACE in selected cases.

    DOI: 10.1111/jgh.13586

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  • [Corrigendum] Loss of Runt‑related transcription factor 3 induces resistance to 5‑fluorouracil and cisplatin in hepatocellular carcinoma. 査読

    Kataoka J, Shiraha H, Horiguchi S, Sawahara H, Uchida D, Nagahara T, Iwamuro M, Morimoto H, Takeuchi Y, Kuwaki K, Onishi H, Nakamura S, Takaki A, Nouso K, Yagi T, Yamamoto K, Okada H

    Oncology reports37 ( 3 ) 1921 - 1921   2017年3月

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  • Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease 査読

    Nozomu Wada, Akinobu Takaki, Fusao Ikeda, Tetsuya Yasunaka, Masahiro Onji, Kazuhiro Nouso, Atsuko Nakatsuka, Jun Wada, Kazuko Koike, Koji Miyahara, Hidenori Shiraha, Kazuhide Yamamoto, Hiroyuki Okada

    HEPATOLOGY INTERNATIONAL11 ( 1 ) 115 - 124   2017年1月

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

    The molecular pathogenesis of non-alcoholic steatohepatitis (NASH) is not well defined. The objective of the present study was to identify disease progression-related cytokines and investigate the molecular pathogenesis of such changes in NASH.
    A study population of 20 non-alcoholic fatty liver (NAFL) and 59 NASH patients diagnosed by liver biopsy and 15 healthy volunteers was recruited. The serum pro- and anti-inflammatory cytokines were measured by a multiple enzyme-linked immunosorbent assay. The hepatic mRNA expressions of cytokines were measured by real-time PCR. A monocyte cell line was stimulated with Toll-like receptor (TLR) ligand under a high glucose and insulin condition, and cellular cytokine mRNA expression was quantified.
    One group of cytokines was higher in NAFL and NASH than in controls, while another group was higher in NASH than in NAFL and controls. The NASH-specific second group included interleukin (IL)-15 and interferon-gamma-inducible protein (IP)-10. In particular, IP-10 was higher in NAFL than in controls and higher in NASH than in NAFL and controls. The sensitivity to diagnose NASH was 90%, with specificity of 50%. Insulin resistance reflecting a high glucose and insulin condition resulted in higher IP-10 mRNA expression in the monocyte cell line only with concomitant TLR-2 stimulation.
    IP-10 is a sensitive marker of the need for liver biopsy. Insulin resistance with bacteria-related TLR-2 stimulation might induce IP-10 production from monocytes. Insulin resistance and intestinal barrier function should be intensively controlled to prevent progression from NAFL to NASH.

    DOI: 10.1007/s12072-016-9773-y

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  • Potential of alpha-fetoprotein as a prognostic marker after curative radiofrequency ablation of hepatocellular carcinoma 査読

    Chihiro Dohi, Kazuhiro Nouso, Koji Miyahara, Yuki Morimoto, Nozomu Wada, Hideaki Kinugasa, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    HEPATOLOGY RESEARCH46 ( 9 ) 916 - 923   2016年8月

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

    AimRecurrence of hepatocellular carcinoma (HCC) is observed frequently, even after curative treatments. The aim of this study is to elucidate the risk factors for recurrence of HCC after radiofrequency ablation (RFA), focusing on the carcinogenic potential of the liver assessed by -fetoprotein (AFP).
    MethodsWe enrolled 357 consecutive patients who underwent complete ablation by RFA for primary HCC (3cm, 3 tumors) and analyzed the correlation between 17 critical parameters, including AFP and HCC recurrence.
    ResultsRecurrence was observed in 236 patients during a mean observation period of 54.3months. Multivariate analysis revealed that multiple tumors (risk ratio [RR]=1.70, 95% confidence interval [CI]=1.27-2.26, P<0.001), high AFP (>10ng/mL, RR=1.45, 95% CI=1.09-1.94, P<0.001) and high des--carboxyprothrombin (>40 mAU/mL, RR=1.52, 95% CI=1.13-2.02, P<0.005) were significantly correlated with recurrence. AFP was selected as a significant factor even when the cut-off level was set lower (5ng/mL). The risk of recurrence increased linearly according to the increase of the lowest AFP level after RFA and the adjusted ratios relative to AFP less than 5ng/mL were 1.56, 2.14, 2.57 and 3.13 in AFP 5-10ng/mL, 10-20ng/mL, 20-50ng/mL and over 50ng/mL, respectively. In addition, the recurrence rate was predicted by the AFP level after RFA, regardless of the level before the treatment.
    ConclusionAFP less than 5ng/mL after curative RFA was an important predictor of a better prognosis and was considered to indicate the low carcinogenic potential of the non-cancerous liver.

    DOI: 10.1111/hepr.12636

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  • Synergistic anti-pancreatic cancer immunological effects by treatment with reduced expression in immortalized cells/dickkopf-3 protein and peripheral blood mononuclear cells 査読

    Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Hiroaki Sawahara, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Masami Watanabe, Akinobu Takaki, Kazuhiro Nouso, Yasutomo Nasu, Hiromi Kumon, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY31 ( 6 ) 1154 - 1159   2016年6月

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

    Background and AimReduced expression in immortalized cells/dickkopf-3 (REIC/DKK3) is a reported tumor suppressor gene and has potential to become an innovative therapy for various cancers. We examined the antitumor immunological effects of human REIC/DKK3 protein against pancreatic cancer.
    MethodsActivation of extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 by REIC/DKK3 protein was assessed in human peripheral blood mononuclear cells using immunoblotting. Pancreatic cancer cell lines (AsPC-1 and MIA Paca-2) were cocultured with peripheral blood mononuclear cells, and the anticancer effects of REIC/DKK3 protein were assessed using the methyl thiazole tetrazolium, cytotoxicity, and enzyme-linked immunospot assays. The antitumor immunological effects of the combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells were also assessed in a pancreatic cancer model using non-obese diabetic/severe combined immunodeficiency mice.
    ResultsThe REIC/DKK3 protein activated extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 in peripheral blood mononuclear cells. REIC/DKK3 protein inhibited in vitro cancer cell viability and enhanced cytotoxicity when incubated with peripheral blood mononuclear cells. REIC/DKK3 protein induced significant production of interferon gamma from lymphocytes incubated with pancreatic cancer cells, indicating that CD8+ T cells were activated in the peripheral blood mononuclear cells when cocultured with AsPC-1 and MIA Paca-2 in the presence of REIC/DKK3 protein. Combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells produced in vivo anticancer immunostimulatory effects on pancreatic cancer cells.
    ConclusionsThe REIC/DKK3 protein and peripheral blood mononuclear cells synergistically enhanced anticancer immunological effects against pancreatic cancer cells. The observed immunomodulatory effect of combined treatment likely occurs in adenovirus-mediated REIC/DKK3 gene therapy and provides important clues to the therapeutic mechanisms involving immune cells.

    DOI: 10.1111/jgh.13259

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  • Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma 査読

    Junro Kataoka, Hidenori Shiraha, Shigeru Horiguchi, Hiroaki Sawahara, Daisuke Uchida, Teruya Nagahara, Masaya Iwamuro, Hiroki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto, Hiroyuki Okada

    ONCOLOGY REPORTS35 ( 5 ) 2576 - 2582   2016年5月

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

    Runt-related transcription factor 3 (RUNX3) is known to function as a tumor suppressor in gastric cancer and other types of cancers, including hepatocellular carcinoma (HCC). However, its role has not been fully elucidated. In the present study, we aimed to evaluate the role of RUNX3 in HCC. We used the human HCC cell lines Hep3B, Huh7 and HLF; RUNX3 cDNA was introduced into Hep3B and Huh7 cells, which were negative for endogenous RUNX3 expression, and RUNX3 siRNA was transfected into HLF cells, which were positive for endogenous RUNX3. We analyzed the expression of RUNX3 and multidrug resistance-associated protein (MRP) by immunoblotting. MTT assays were used to determine the effects of RUNX3 expression on 5-fluorouracil (5-FU) and cisplatin (CDDP) sensitivity. Finally, 23 HCC specimens resected from patients with HCC at Okayama University Hospital were analyzed, and correlations among immunohistochemical expression of RUNX3 protein and MRP protein were evaluated in these specimens. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, MRP3 and MRP5 in the RUNX3-negative cells, whereas knockdown of RUNX3 in the HLF cells stimulated the expression of these MRPs. An inverse correlation between RUNX3 and MRP expression was observed in the HCC tissues. Importantly, loss of RUNX3 expression contributed to 5-FU and CDDP resistance by inducing MRP expression. These data have important implications in the study of chemotherapy resistance in HCC.

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  • Promising Therapeutic Efficacy of a Novel REIC/Dkk-3 Expressing Adenoviral Vector for Hepatocellular Carcinoma 査読

    Hiroaki Sawahara, Shiraha Hidenori, Uchida Daisuke, Sakaguchi Masakiyo, Watanabe Masami, Nasu Yasutomo, Kumon Hiromi, Okada Hiroyuki

    GASTROENTEROLOGY150 ( 4 ) S1153   2016年4月

  • Development of a Novel REIC/DKK-3-Encoding Adenoviral Agent: Its Robust and Promising Therapeutic Effects in Pancreatic Cancer 査読

    Uchida Daisuke, Shiraha Hidenori, Kato Hironari, Hiroaki Sawahara, Sakaguchi Masakiyo, Watanabe Masami, Nasu Yasutomo, Kumon Hiromi, Okada Hiroyuki

    GASTROENTEROLOGY150 ( 4 ) S294   2016年4月

  • An Energy Dispersive X-ray Spectroscopy Analysis of Elemental Changes of a Persimmon Phytobezoar Dissolved in Coca-Cola 査読

    Masaya Iwamuro, Haruo Urata, Reiji Higashi, Masahiro Nakagawa, Shin Ishikawa, Hidenori Shiraha, Hiroyuki Okada

    INTERNAL MEDICINE55 ( 18 ) 2611 - 2615   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    To investigate the mechanism of phytobezoar dissolution by Coca-Cola (R), persimmon phytobezoar pieces removed from a 60-year-old Japanese woman were analyzed by energy dispersive X-ray spectroscopy. The amount of calcium significantly decreased after dissolution treatment using Coca-Cola (R), suggesting a potential contribution of calcium to dissolution mechanisms. Moreover, immersion in Coca-Cola (R) for 120 hours on the exterior surface revealed that Coca-Cola (R) did not permeate persimmon phytobezoars. This is the first study to investigate the mechanisms of persimmon phytobezoar permeability and dissolution induced by Coca-Cola (R).

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  • Oxidative stress balance is dysregulated and represents an additional target for treating cholangiocarcinoma 査読

    Daisuke Uchida, Akinobu Takaki, Hisashi Ishikawa, Yasuko Tomono, Hironari Kato, Koichiro Tsutsumi, Naofumi Tamaki, Takayuki Maruyama, Takaaki Tomofuji, Ryuichiro Tsuzaki, Tetsuya Yasunaka, Kazuko Koike, Hiroshi Matsushita, Fusao Ikeda, Yasuhiro Miyake, Hidenori Shiraha, Kazuhiro Nouso, Ryuichi Yoshida, Yuzo Umeda, Susumu Shinoura, Takahito Yagi, Toshiyoshi Fujiwara, Manabu Morita, Masaki Fukushima, Kazuhide Yamamoto, Hiroyuki Okada

    FREE RADICAL RESEARCH50 ( 7 ) 732 - 743   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    Background: Pancreatico-biliary malignancies exhibit similar characteristics, including obesity-related features and poor prognosis, and require new treatment strategies. Oxidative stress is known to induce DNA damage and carcinogenesis, and its reduction is viewed as being favorable. However, it also has anti-infection and anti-cancer functions that need to be maintained. To reveal the effect of oxidative stress on cancer progression, we evaluated oxidative stress and anti-oxidative balance in pancreatic cancer (PC) and cholangiocarcinoma (CC) patients, as well as the effect of add-on antioxidant treatment to chemotherapy in a mouse cholangiocarcinoma model.
    Methods: We recruited 84 CC and 80 PC patients who were admitted to our hospital. Serum levels of reactive oxygen metabolites (ROM) and the anti-oxidative OXY-adsorbent test were determined and the balance of these tests was defined as an oxidative index. A diabetic mouse-based cholangiocarcinoma model was utilized to evaluate the effects of add-on antioxidant therapy on cholangiocarcinoma chemotherapy.
    Results: Serum ROM was higher and anti-oxidant OXY was lower in CC patients with poor outcomes. These parameters were not significantly different in PC patients. In mice, vitamin E administration induced antioxidant hemeoxygenase (HO)-1 protein expression in cancer tissue, while the number of stem-like cells increased. L-carnitine administration improved intestinal microbiome and biliary acid balance, upregulated the hepatic mitochondrial membrane uptake related gene Cpt1 in non-cancerous tissue, and did not alter stem-like cell numbers.
    Conclusion: Oxidative stress balance was dysregulated in cholangiocarcinoma with poor outcome. The mitochondrial function-supporting agent L-carnitine is a good candidate to control oxidative stress conditions.

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  • Low frequency of drug-resistant virus did not affect the therapeutic efficacy in daclatasvir plus asunaprevir therapy in patients with chronic HCV genotype-1 infection 査読

    Hideaki Kinugasa, Fusao Ikeda, Kouichi Takaguchi, Chizuru Mori, Takehiro Matsubara, Hidenori Shiraha, Akinobu Takaki, Yoshiaki Iwasaki, Shinichi Toyooka, Kazuhide Yamamoto

    ANTIVIRAL THERAPY21 ( 1 ) 37 - 44   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT MEDICAL PRESS LTD  

    Background: The efficacy of a direct-acting antiviral agent (DAA) is compromised by the development of drug resistance. The associations between resistance-associated virus (RAV) and therapeutic outcomes have not been well-understood.
    Methods: A total of 30 patients with HCV genotype-1b were enrolled and treated for 24 weeks with asunaprevir (ASV) and daclatasvir (DCV). Viral sequences in non-structural (NS) regions 3 and 5A in serum and liver tissue before treatment were examined with direct sequencing, next-generation sequencing (NGS) and the PCR-invader method to evaluate the importance of drug-resistance in the prediction of the outcomes of ASV plus DCV therapy.
    Results: Of 30 patients (22 treatment-naive patients, 2 interferon-intolerant patients and 6 non-responders), 25 patients (83.3%) achieved sustained virological response (SVR) 24 weeks after the treatment. Viral breakthrough occurred in three treatment-naive patients and one non-responder. One treatment-naive patient experienced viral relapse. Among 25 patients without RAV, 24 obtained SVR, whereas 5 patients had RAV with a 1.3 to 88% frequency, resulting in various therapeutic outcomes. As for HCV compartments, similar RAVs were detected in serum and liver tissue for a patient obtaining SVR despite HCV NS5A Y93H and another developed viral breakthrough although no RAV was detected. Direct sequencing could not detect RAVs in low frequency (1.3 to 12%) for three of four patients.
    Conclusions: Low frequency of RAVs might not affect the outcomes of ASV plus DCV therapy. Deep sequencing and PCR-invader methods can detect clinically significant RAVs for ASV plus DCV therapy.

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  • A case of unresectable combined hepatocellular cholangiocarcinoma showing favorable response to LFP therapy 査読

    Sayuri Kato, Yasuto Takeuchi, Nozomu Wada, Yuuki Morimoto, Kenji Kuwaki, Hideki Ohnishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    Journal of Japanese Society of Gastroenterology113 ( 12 ) 2050 - 2056   2016年

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

    A woman in her 50s was admitted to our hospital because of multiple tumors detected in her liver. She was diagnosed with combined hepatocellular cholangiocarcinoma using gadolinium-ethoxybenzyldiethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biopsy of the liver tumors. We judged the tumors to be unresectable because they were found in both lobes of the liver, with a tumor thrombus being found in the main left portal vein. The pathological findings showed that the tumors exhibited characteristics of hepatocellular carcinoma Therefore, sorafenib was administered
    however, 6 months later, the disease progressed. Consequently, she received second-line chemotherapy with a one-shot intra-arterial injection of cisplatin, but this too was ineffective, and her general condition worsened. As hence, we changed the regimen to 5-fluorouracil continuous infusion and consecutive low dose cisplatin (LFP) therapy. After one cycle of chemotherapy with LFP, Gd-EOB-DTPA-enhanced MRI showed markedly decreased sizes and numbers of tumors. To date, she has completed six cycles of LFP therapy, and almost all her tumors are no longer visible on MRI. She has recovered to a good state and has achieved long-term survival. Thus, this case indicates that although LFP therapy is generally selected for cases of advanced hepatocellular carcinoma, it also appears to be effective for long-term disease control in cases of hepatocellular cholangiocarcinoma.

    DOI: 10.11405/nisshoshi.113.2050

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  • Alteration of N-glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma 査読

    Koji Miyahara, Kazuhiro Nouso, Chihiro Dohi, Yuki Morimoto, Hideaki Kinugasa, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH45 ( 9 ) 986 - 993   2015年9月

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

    AimMost of the modification of N-glycosylation reported in cancers including hepatocellular carcinoma (HCC) were based on the examinations of a small number of patients or particular proteins. The aim of this study is to reveal changes in whole serum N-glycan profiles systematically during the process of hepatocarcinogenesis and to elucidate their clinical application.
    MethodsWe analyzed sera from 105 patients with chronic hepatitis/liver cirrhosis (CH/LC) and age-/sex-matched healthy volunteers (HLT), as well as from 114 patients with HCC. Serum N-glycan profiles were measured comprehensively by a new, quantitative, high-throughput method and compared with clinical parameters.
    ResultsThe total amount of N-glycan expression was significantly higher in patients with CH/LC than in HLT; however, no differences were observed between CH/LC and HCC patients. In HCC patients, multi-antennary glycans with fucose residues, particularly m/z 3195, were increased compared with CH/LC patients. The expression of m/z 3195 was high, especially in patients with a high number of intrahepatic lesions (>3), large tumor size (>3cm), macroscopic vascular invasion or metastasis. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) showed a higher area under the receiver-operator curve of 0.810 than any other single glycan to distinguish HCC from CH/LC.
    ConclusionWe demonstrate the full spectrum of the alterations of serum N-glycans comprehensively in patients with liver disease, and elucidate the possible use of glycans as novel biomarkers of liver disease progression.

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  • Hepatic stellate cells promote upregulation of epithelial cell adhesion molecule and epithelial-mesenchymal transition in hepatic cancer cells 査読

    Teruya Nagahara, Hidenori Shiraha, Hiroaki Sawahara, Daisuke Uchida, Yasuto Takeuchi, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Takeshi Kuwaki, Hideki Onishi, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto

    ONCOLOGY REPORTS34 ( 3 ) 1169 - 1177   2015年9月

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

    Microenvironment plays an important role in epithelial-mesenchymal transition (EMT) and sternness of cells in hepatocellular carcinoma (HCC). Epithelial cell adhesion molecule (EpCAM) is known as a tumor stemness marker of HCC. To investigate the relationship between microenvironment and sternness, we performed an in vitro co-culture assay. Four HCC cell lines (HepG2, Hep3B, HuH-7 and PLC/PRF/5) were co-cultured with the TWNT-1 immortalized hepatic stellate cells (HSCs), which create a microenvironment with HCC. Cell proliferation ability was analyzed by flow cytometry (FCM) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while migration ability was assessed by a wound healing assay. Expression of EpCAM was analyzed by immunoblotting and FCM. HCC cell lines were co-cultured with TWNT-1 treated with small interfering RNA (siRNA) for TGF-beta and HB-EGF; we then analyzed proliferation, migration ability and protein expression using the methods described above. Proliferation ability was unchanged in HCC cell lines co-cultured with TWNT-1. Migration ability was increased in HCC cell lines (HepG2, Hep3B, HuH-7 and PLC/PRF/5) directly (216.2 +/- 67.0, 61.0 +/- 22.0, 124.0 +/- 66.2 and 51.5 +/- 40.3%) and indirectly (102.5 +/- 22.0, 84.6 +/- 30.9, 86.1 +/- 25.7 and 73.9 +/- 29.7%) co-cultured with TWNT-1 compared with the HCC uni-culture. Immunoblot analysis revealed increased EpCAM expression in the HCC cell lines co-cultured with TWNT-1. Flow cytometry revealed that the population of E-cadherin(-)/N-cadherin(+) and EpCAM-positive cells increased and accordingly, EMT and stemness in the HCC cell line were activated. These results were similar in the directly and indirectly co-cultured samples, indicating that humoral factors were at play. Conversely, HCC cell lines co-cultured with siRNA-treated TWNT-1 showed decreased migration ability, a decreased population of EpCAM-positive and E-cadherin(-)/N-cadherin(+) cells. Taken together, humoral factors secreted from TWNT-1 promote upregulation of EpCAM and EMT in hepatic cancer cells.

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  • Local Recurrence and Complications after Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma: A Retrospective Cohort Study Focused on Tumor Location 査読

    Junichi Toshimori, Kazuhiro Nouso, Shinichiro Nakamura, Nozomu Wada, Yuki Morimoto, Yasuto Takeuchi, Tetsuya Yasunaka, Kenji Kuwaki, Hideki Ohnishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA69 ( 4 ) 219 - 226   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    We conducted a retrospective cohort study to investigate the predisposing factors for local recurrence and complications after percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). HCC patients (n = 397) consecutively treated with RFA (256 males, 141 females, median age 69 years) were enrolled. In these patients, 1,455 nodules (median size 17 mm) were ablated. Predisposing factors for overall recurrence and local recurrence in the context of tumor location and complications were examined. Local recurrence was observed for 113 of the 1,455 nodules. The 1-, 3- and 5-year local recurrence rates were 2.2%, 7.4% and 9.5%, respectively. A multivariate Cox proportional hazard analysis revealed that large tumor size (> 2cm), tumor location (adjacent to the major portal branch or hepatic vein), and small ablated margin (< 3mm) were independent predisposing factors for local recurrence after RFA (HR = 1.70-2.81). Tumor location (adjacent to the major portal branch, hepatic vein, or diaphragm) was also revealed as a risk factor for liver damage due to RFA. HCC adjacent to the major portal vein or hepatic vein was associated with a higher risk for local recurrence and for complications; therefore, special precautions are necessary when applying RFA to HCC near vessels even when the tumors are located at an easy-to-puncture site.

    DOI: 10.18926/AMO/53558

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  • Enhancement of Programmed Death Ligand 2 on Hepatitis C Virus Infected Hepatocytes by Calcineurin Inhibitors 査読

    Kazuko Koike, Akinobu Takaki, Takahito Yagi, Yoshiaki Iwasaki, Tetsuya Yasunaka, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Sato, Daisuke Nobuoka, Masashi Utsumi, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    TRANSPLANTATION99 ( 7 ) 1447 - 1454   2015年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Background. Post orthotopic liver transplantation (OLT) viral hepatitis is an immunological condition where immune cells induce hepatitis during conditions of immune-suppression. The immune-regulatory programmed death-1 (PD-1)/PD-ligand 1 system is acknowledged to play important roles in immune-mediated diseases. However, the PD-1/PD-L2 interaction is not well characterized, with PD-L2 also exhibiting an immunostimulatory function. We hypothesized that this atypical molecule could affect the recurrence of post-OLT hepatitis. To test this hypothesis, we conducted immunohistochemical staining analysis and in vitro analysis of PD-L2. Methods. The expression of PD-L2 was evaluated in liver biopsy specimens from patients with chronic hepatitis B (n = 15), post-OLT hepatitis B (n = 8), chronic hepatitis C (n = 48), and post-OLT hepatitis C (CH-C-OLT) (n = 14). The effect of calcineurin inhibitors (CNIs) and hepatitis C virus (HCV) on PD-L2 expression was investigated in hepatoma cell lines. Results. The PD-L2 was highly expressed on CH-C-OLT hepatocytes. Treatment of hepatoma cell lines with CNIs resulted in increased PD-L2 expression, especially in combination with HCV core or NS3 protein. Transfection of cell lines with PD-L2 containing plasmid resulted in high intercellular adhesion molecule-1 (ICAM-1) expression, which might enhance hepatitis activity. Conclusions. The PD-L2 is highly expressed on CH-C-OLT hepatocytes, whereas HCV proteins, in combination with CNIs, induce high expression of PD-L2 resulting in elevated expression of ICAM-1. These findings demonstrate the effect of CNIs on inducing PD-L2 and subsequent ICAM-1 expression, effects that may produce inflammatory cell infiltration in post-OLT hepatitis C.

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  • Serum N-glycan profiles in patients with intraductal papillary mucinous neoplasms of the pancreas 査読

    Yutaka Akimoto, Kazuhiro Nouso, Hironari Kato, Koji Miyahara, Chihiro Dohi, Yuki Morimoto, Hideaki Kinugasa, Takeshi Tomoda, Naoki Yamamoto, Koichiro Tsutsumi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    PANCREATOLOGY15 ( 4 ) 432 - 438   2015年7月

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

    Background/objectives: Diagnosing the invasiveness of intraductal papillary mucinous neoplasms (IPMNs) is difficult, especially by blood test. Alterations in serum glycan profiles have been reported for several cancers, but changes in serum glycan profiles have not been investigated in patients with IPMNs. The objectives of this study were to determine the serum N-glycan profile and to investigate its clinical utility in patients with IPMNs.
    Methods: We measured serum N-glycan profiles in 79 patients with IPMNs, including 13 invasive IPMNs, by performing comprehensive glycome analysis and assessed the relationship between N-glycan changes and clinical parameters.
    Results: Seventy glycans were identified and their expression profiles were significantly different depending on the cyst size, the presence of an enhancing solid component, and the histological grade of the IPMN. Nine glycans were highly expressed in patients with invasive IPMNs. The glycan m/z 3195, which is a fucosylated tri-antennary glycan, had the highest diagnostic value for distinguishing invasive IPMNs from non-invasive IPMNs (area under the receiver operating characteristic curve = 0.803). Multivariate analyses revealed high levels of m/z 3195 [odds ratio (OR), 20.5; 95% confidence interval (CI) 2.60-486.4] and the presence of enhancing solid components (OR, 35.8; 95% Cl, 5.39-409.6) were significant risk factors for invasive IPMNs.
    Conclusions: We performed a comprehensive evaluation of the changes in serum N-glycan profiles in patients with IPMNs for the first time. We determined that increased expression of fucosylated complex-type glycans, especially m/z 3195, is a potential marker for invasive IPMNs. Copyright (C) 2015, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

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  • Prognostic Value of Altered N-Glycosylation of Circulating Glycoproteins in Patients With Unresectable Pancreatic Cancer Treated With Gemcitabine 査読

    Koji Miyahara, Kazuhiro Nouso, Yuki Morimoto, Hideaki Kinugasa, Hironari Kato, Naoki Yamamoto, Koichiro Tsutsumi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Taku Nakahara, Yoshiaki Miura, Hidehisa Asada, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    PANCREAS44 ( 4 ) 551 - 556   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objectives: The objectives of this study were to examine the whole serum N-glycan profile of patients with unresectable pancreatic cancer and to evaluate the ability of glycans to predict gemcitabine treatment efficacy and patient survival.
    Methods: We collected serum from 52 patients with advanced pancreatic cancer before they began gemcitabine monotherapy. The serum glycan profile was measured through comprehensive quantitative high-throughput glycome analysis and compared with the treatment efficacy and patient survival.
    Results: Of the 61 glycans detected, the serum levels of glycan 4310 (molecular weight [m/z] 1549.566), 6301 (m/z 2032.724), and 9200 (m/z 2010.692) were high in patients with a short time to tumor progression (TTP). Multivariate analysis revealed that a high glycan 9200 concentration was an independent risk factor for shorter TTP (hazard ratio, 2.11; 95% confidence interval, 1.07-4.17) and poor overall survival (hazard ratio, 2.56; 95% confidence interval, 1.08-6.19). The median TTP of patients with up-regulation of 9200 after gemcitabine treatment was shorter than for the remaining patients (91 vs 301 days; P = 0.0005). A similar relationship was observed for overall survival (median, 181 vs 561 days; P = 0.001).
    Conclusions: Glycan 9200 is a possible biomarker predicting gemcitabine efficacy survival in patients with unresectable pancreatic cancer.

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  • Use of non-invasive serum glycan markers to distinguish non-alcoholic steatohepatitis from simple steatosis 査読

    Yasushi Yamasaki, Kazuhiro Nouso, Koji Miyahara, Nozomu Wada, Chihiro Dohi, Yuki Morimoto, Hideaki Kinugasa, Yasuto Takeuchi, Tetsuya Yasunaka, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Yoshiaki Iwasaki, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY30 ( 3 ) 528 - 534   2015年3月

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

    Background and AimsSerum glycans have been reported to be promising diagnostic markers for many inflammatory diseases and cancers. The aims of this study were to investigate whole glycan expression in patients with non-alcoholic fatty liver diseases and to evaluate the potential use of glycan profiles as new clinical biomarkers to distinguish non-alcoholic steatohepatitis (NASH) from simple steatosis (SS).
    MethodsWe collected sera from 42 histologically proven NASH and 15 SS patients prior to treatment. Serum glycan profiles were measured by comprehensive, quantitative, high-throughput glycome analysis, and diagnostic values of serum glycans for NASH prediction were examined.
    ResultsAmong the 41 serum glycans examined, the expression levels of 8 glycans in NASH were significantly higher than those of SS. Out of these eight glycans, three glycans (m/z 1955, 2032, and 2584) showed high areas under the receiver operating characteristic curve (0.833, 0.863, and 0.866, respectively) for distinguishing NASH from SS. In multivariate analyses with clinical parameters and serum glycans, these three glycans were significant predictive factors for distinguishing NASH from SS. The odds ratio of m/z 1955, 2032, and 2584 were 48.5, 6.46, and 11.8, respectively. These glycans also correlated significantly with lobular inflammation, ballooning, and fibrosis, but not with steatosis.
    ConclusionWe clearly demonstrated whole-serum glycan profiles in NASH patients, and the feasibility of serum glycans (m/z 1955, 2032, and 2584) as new noninvasive biomarkers for distinguishing NASH from SS.

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  • TLR4, TLR9, and NLRP3 in biliary epithelial cells of primary sclerosing cholangitis: Relationship with clinical characteristics 査読

    Hiroshi Matsushita, Yasuhiro Miyake, Akinobu Takaki, Tetsuya Yasunaka, Kazuko Koike, Fusao Ikeda, Hidenori Shiraha, Kazuhiro Nouso, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY30 ( 3 ) 600 - 608   2015年3月

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

    Background and AimInappropriate innate immune responses have been suggested to contribute to the pathogenesis of primary sclerosing cholangitis (PSC). We evaluated the associations of expressions of toll-like receptor (TLR) 4, TLR9, and nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family pyrin domain containing 3 (NLRP3) in the biliary epithelial cells (BECs) with clinical features of PSC patients.
    MethodsWe retrospectively evaluated the expressions of TLR4, TLR9, and NLRP3 in the intrahepatic BECs by immunohistochemical staining in 21 PSC patients and 10 normal controls. In PSC, 17 patients underwent liver biopsy, and, in the other four patients, liver specimens were obtained at the time of liver transplantation.
    ResultsTLR9 expressions in BECs were higher in PSC patients than in normal controls. TLR9 expressions were correlated with Ludwig fibrosis scores in PSC patients. TLR4 and NLRP3 expressions were similar between PSC patients and normal controls. Seventeen PSC patients undergoing liver biopsy were followed up during a median period of 55.7 months. Four reached to liver transplantation and four developed cholangiocarcinoma. Patients developing cholangiocarcinoma showed lower NLRP3 expressions than the others. Patients reaching to liver transplantation showed higher TLR9 expressions. Expression levels of TLR9 and NLRP3 were not correlated with liver biochemical tests and Mayo risk scores.
    ConclusionsIn PSC, excessive immune responses through TLR9 signaling may be associated with the disease progression. Insufficient immune response through NLRP3 signaling may be associated with the development of cholangiocarcinoma. Evaluation of TLR9 and NLRP3 expressions in BECs may be useful for predicting the prognosis as an auxiliary marker.

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  • Efficacy of hepatic arterial infusion chemotherapy in combination with irradiation for advanced hepatocellular carcinoma with portal vein invasion 査読

    Hideki Onishi, Kazuhiro Nouso, Shinichiro Nakamura, Kuniaki Katsui, Nozomu Wada, Yuki Morimoto, Koji Miyahara, Yasuto Takeuchi, Kenji Kuwaki, Tetsuya Yasunaka, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Yoshiyuki Kobayashi, Kohsaku Sakaguchi, Susumu Kanazawa, Kazuhide Yamamoto

    HEPATOLOGY INTERNATIONAL9 ( 1 ) 105 - 112   2015年1月

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

    The presence of portal vein tumor thrombosis (PVTT) is a poor prognostic factor for patients with hepatocellular carcinomas (HCC). The purpose of this study was to determine the treatment effect of irradiation in combination with hepatic arterial infusion chemotherapy (HAIC) for these patients.
    We retrospectively examined the outcome of 67 HCC patients with PVTT of the main trunk or first branch who received HAIC alone or with concurrent irradiation for PVTT (CCRT).
    Thirty-four patients received HAIC, and 33 patients received CCRT. The time to progression (TTP) of PVTT in the CCRT group was significantly longer than in the HAIC group (p < 0.01), and the TTP of intrahepatic nodules in the CCRT group tended to be longer than in the HAIC group (p = 0.06). The objective response rates of intrahepatic nodules (52 vs. 18 %, p < 0.01) and PVTT (45 vs. 18 %, p = 0.01) were both significantly higher in the CCRT group than in the HAIC group, respectively. No significant difference in overall survival was found between the two groups (p = 0.14); however, the median survival time in the CCRT group was longer than that in the HAIC group (12.4 vs. 5.7 months, respectively).
    CCRT might be a promising treatment for advanced-stage HCC with PVTT. CCRT prolonged the TTP of intrahepatic nodules and PVTT, and it improved the objective response rate of intrahepatic nodules and PVTT.

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  • Serum Oxidative/anti-oxidative Stress Balance Is Dysregulated in Potentially Pulmonary Hypertensive Patients with Liver Cirrhosis: A Case Control Study 査読

    Masako Terao, Akinobu Takaki, Takayuki Maruyama, Hiroki Oe, Tetsuya Yasunaka, Naofumi Tamaki, Kazufumi Nakamura, Takaaki Tomofuji, Takahito Yagi, Hiroshi Sadamori, Yuzo Umeda, Susumu Shinoura, Ryuichi Yoshida, Kazuhiro Nouso, Daisuke Ekuni, Kazuko Koike, Fusao Ikeda, Hidenori Shiraha, Manabu Morita, Hiroshi Ito, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    INTERNAL MEDICINE54 ( 22 ) 2815 - 2826   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    Objective Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH.
    Methods We recruited patients with decompensated cirrhosis (n = 69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolararterial oxygen gradient (AaDO(2)) >= 15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient >= 25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXY-adsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a cross-sectional study.
    Results Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p = 0.037) and higher oxidative index values (p = 0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p = 0.049). The potential POPH patients exhibited elevated AaDO(2), suggesting the presence of pulmonary shunting.
    Conclusion Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.

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  • Involvement of platelets in extrahepatic metastasis of hepatocellular carcinoma 査読

    Yuki Morimoto, Kazuhiro Nouso, Nozomu Wada, Yasuto Takeuchi, Hideaki Kinugasa, Koji Miyahara, Tetsuya Yasunaka, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH44 ( 14 ) E353 - E359   2014年12月

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

    AimRecently, a relationship between platelets and cancer metastasis has been reported. The aim of this study is to elucidate the risk factors for extrahepatic metastasis (EHM), with emphasis on association with platelets in patients, with hepatocellular carcinoma (HCC).
    MethodsWe examined risk factors for EHM in 1613 consecutive, newly diagnosed HCC patients by logistic regression analysis (case-control study). We also examined the factors by Cox proportional hazard model in a retrospective cohort fashion in 803 patients who received non-curative treatment for HCC.
    ResultsIn the case-control study, multivariate analysis revealed that high platelet counts (odds ratio [OR]=4.84; 95% confidence interval [CI]=1.29-29.54; P=0.01), high tumor number and the presence of macroscopic vascular invasion were significantly associated with EHM. In the cohort study, EHM was diagnosed in 71 patients during the study period (mean observation time=23.3 months). On multivariate analysis, high tumor number, high des--carboxyprothrombin (DCP) and Child-Pugh class A were significantly correlated with EHM, and the patients with high platelet counts tended to develop EHM (OR=1.73; 95% CI=0.99-3.14; P=0.055).
    ConclusionHCC patients with high platelet counts, as well as large numbers of tumors, high serum DCP and Child-Pugh class A, are at risk for EHM.

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  • Ultrastructural Analysis of an Enterolith Composed of Deoxycholic Acid 査読

    Masaya Iwamuro, Yuichi Miyashima, Takahiro Yoshioka, Toshihiro Murata, Yoshio Miyabe, Yoshinari Kawai, Haruo Urata, Hidenori Shiraha, Hiroyuki Okada, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA68 ( 6 ) 369 - 374   2014年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    A 67-year-old Japanese man underwent enterotomy because of enterolith ileus. Component analysis by infrared spectroscopy revealed that the enterolith was composed of a high concentration of deoxycholic acid. We further analyzed and compared the ultrastructure of the enterolith and a commercially available powdered form of deoxycholic acid by means of scanning electron microscopy and energy dispersive X-ray spectroscopy. Energy dispersive X-ray spectroscopy analysis revealed that the ratios of carbon and oxygen in the enterolith were equal to those in the deoxycholic acid powder. Scanning electron microscopy analysis showed rectangular prism-shaped particles on the surface of the enterolith. This structure was similar to that of the deoxycholic acid powder. The surgically removed enterolith had a twisted and coiled appearance. Possible mechanisms underlying the formation of this unique form are discussed.

    DOI: 10.18926/AMO/53026

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  • Prevention of vagotonia and pain during radiofrequency ablation of liver tumors 査読

    Shinichiro Nakamura, Kazuhiro Nouso, Hideki Onishi, Kenji Kuwaki, Hiroaki Hagihara, Yasuto Takeuchi, Nozomu Wada, Yuki Morimoto, Koji Miyahara, Tetsuya Yasunaka, Fusao Ikeda, Yasuhiro Miyake, Yoshiyuki Kobayashi, Hidenori Shiraha, Shinichi Ishikawa, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH44 ( 13 ) 1367 - 1370   2014年12月

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

    Radiofrequency ablation (RFA) is frequently used to treat early stage hepatocellular carcinoma. Two of the most cumbersome side-effects of the ablation procedure are intractable pain and vagotonia when deep sedation is not used. We describe local injection of anesthetic into Glisson's sheath as a new technique for overcoming these problems. Lidocaine was injected into Glisson's sheath when radiofrequency ablation of hepatocellular carcinomas, which were located adjacent to Glisson's sheath, could not be continued due to severe pain (n=8) or bradycardia (n=3). In all three patients who showed vagotonia with bradycardia during the ablations, injection of lidocaine prevented bradycardia, allowing completion of the radiofrequency ablation. Pain was reduced in all eight patients who experienced pain during ablation. No side-effects were observed during the procedures. Injection of anesthetic into Glisson's sheath is simple and effective for reducing intractable pain and vagotonia associated with RFA.

    DOI: 10.1111/hepr.12321

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  • Nursing Support Increases the Efficacy of Interferon Therapy in Patients with Chronic Hepatitis C 査読

    Shihoko Namba, Kayoko Miyake, Fusao Ikeda, Tomoko Hazama, Yu Hitobe, Noriko Yamasaki, Hidenori Shiraha, Akinobu Takaki, Kazuhiro Nouso, Yoshiaki Iwasaki, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA68 ( 5 ) 263 - 268   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Nursing support might help patients with chronic hepatitis C (CHC) remain in good mental and physical condition during interferon (IFN) therapy. However, the effects of nursing support have not been studied adequately in this context. This case-control study evaluated the effects of nursing support during IFN therapy. Twenty-four CHC patients who received pegylated IFN and ribavirin were enrolled. Nurses advised patients on the maintenance of their mental and physical condition at weekly visits, based on the results of written questionnaires. An additional 24 patients who received IFN therapy without nursing support and who were matched for age, sex, platelet count, viral serogroup and IFN regimen were selected with propensity score matching as controls. The patients with nursing support during IFN therapy achieved higher sustained virological responses (79%) than those without nursing support (58%). Adherence to the IFN and ribavirin regimens at 24 weeks of therapy were slightly higher in the patients with nursing support than those without it, but these differences were not statistically significant. Adherence to ribavirin after 24 weeks of therapy was significantly higher in those with nursing support than those without it (93% and 66%, p = 0.045). These results suggested that nursing support services could contribute to the virological responses of CHC patients by promoting drug-regimen adherence.

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  • Hepatitis C Virus-specific T-cell Response Correlates with Hepatitis Activity and Donor IL28B Genotype Early after Liver Transplantation 査読

    Ryuichiro Tsuzaki, Akinobu Takaki, Takahito Yagi, Fusao Ikeda, Kazuko Koike, Yoshiaki Iwasaki, Hidenori Shiraha, Yasuhiro Miyake, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Masashi Utsumi, Eiichi Nakayama, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA68 ( 5 ) 291 - 302   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-specific immune responses by measuring the peripheral blood mononuclear cell-derived HCV-specific interferon-gamma (IFN-gamma) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At > 3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-specific immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect.

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  • Ultrastructural analysis of a gastric persimmon phytobezoar 査読

    Masaya Iwamuro, Haruo Urata, Masumi Furutani, Yoshinari Kawai, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Kazuhide Yamamoto

    CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY38 ( 4 ) E85 - E87   2014年9月

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    記述言語:英語   出版者・発行元:ELSEVIER MASSON  

    DOI: 10.1016/j.clinre.2013.11.005

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  • L-Carnitine Prevents Progression of Non-Alcoholic Steatohepatitis in a Mouse Model with Upregulation of Mitochondrial Pathway 査読

    Hisashi Ishikawa, Akinobu Takaki, Ryuichiro Tsuzaki, Tetsuya Yasunaka, Kazuko Koike, Yasuyuki Shimomura, Hiroyuki Seki, Hiroshi Matsushita, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Kazuhiro Nouso, Kazuhide Yamamoto

    PLOS ONE9 ( 7 )   2014年7月

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

    Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC). Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid), an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1) high-fat diet (HFD) (control group); 2) HFD mixed with 0.28% L-carnitine (L-carnitine group); and 3) HFD mixed with 0.01% alpha-tocopherol (alpha-tocopherol group). After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial beta-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although alpha-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by upregulating the mitochondrial beta-oxidation and redox system.

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  • Potential of adenovirus-mediated REIC/Dkk-3 gene therapy for use in the treatment of pancreatic cancer 査読

    Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Masami Watanabe, Akinobu Takaki, Kazuhiro Nouso, Yasutomo Nasu, Takahito Yagi, Hiromi Kumon, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY29 ( 5 ) 973 - 983   2014年5月

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

    Background and AimThe reduced expression in immortalized cells REIC/the dickkopf 3 (Dkk-3) gene, tumor suppressor gene, is downregulated in various malignant tumors. In a prostate cancer study, an adenovirus vector carrying the REIC/Dkk-3 gene (Ad-REIC) induces apoptosis. In the current study, we examined the effects of REIC/Dkk-3 gene therapy in pancreatic cancer.
    MethodsREIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry in the pancreatic cancer cell lines (ASPC1, MIAPaCa2, Panc1, BxPC3, SUIT-2, KLM1, and T3M4) and pancreatic cancer tissues. The Ad-REIC agent was used to investigate the apoptotic effect in vitro and antitumor effects in vivo. We also assessed the therapeutic effects of Ad-REIC therapy with gemcitabine.
    ResultsThe REIC/Dkk-3 expression was lost in the pancreatic cancer cell lines and decreased in pancreatic cancer tissues. Ad-REIC induced apoptosis and inhibited cell growth in the ASPC1 and MIAPaCa2 lines in vitro, and Ad-REIC inhibited tumor growth in the mouse xenograft model using ASPC1 cells. The antitumor effect was further enhanced in combination with gemcitabine. This synergistic effect may be caused by the suppression of autophagy via the enhancement of mammalian target of rapamycin signaling.
    ConclusionsAd-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer.

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  • Efficacy of sorafenib beyond first progression in patients with metastatic hepatocellular carcinoma 査読

    Koji Miyahara, Kazuhiro Nouso, Yuki Morimoto, Yasuto Takeuchi, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Shouta Iwadou, Yoshiyuki Kobayashi, Koichi Takaguchi, Yoshitaka Takuma, Hiroyuki Takabatake, Kohsaku Sakaguchi, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH44 ( 3 ) 296 - 301   2014年3月

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

    Aim
    We investigated whether continuous sorafenib administration keeps suppressing the growth of hepatocellular carcinoma (HCC) after first progressive disease (PD), and whether it prolongs patients' survival.
    Methods
    The size of metastatic lesions was measured in 36 patients with advanced HCC treated with sorafenib. The tumor growth rates before and after radiological PD as well as survival were compared between the patients who continued (n = 23) and stopped (n = 13) sorafenib at first radiological PD.
    Results
    The growth rate did not differ between before and after PD in patients who continued sorafenib, while it increased after PD in patients who stopped sorafenib at PD (P = 0.002). Survival beyond first progression was longer in patients who continued sorafenib than in those who stopped it at PD (P = 0.012), and this tendency was observed even when the analysis was limited to Child-Pugh class A patients (P = 0.085).
    Conclusion
    Sorafenib administration beyond first radiological PD could continuously suppress HCC growth and may have survival benefit.

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  • In Vitro Analysis of Gastric Phytobezoar Dissolubility by Coca-Cola, Coca-Cola Zero, Cellulase, and Papain 査読

    Masaya Iwamuro, Yoshinari Kawai, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Kazuhide Yamamoto

    JOURNAL OF CLINICAL GASTROENTEROLOGY48 ( 2 ) 190 - 191   2014年2月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1097/MCG.0b013e3182a39116

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  • Anti-programmed cell death-1 antibody as a new serological marker for type 1 autoimmune hepatitis 査読

    Kazuyuki Matsumoto, Yasuhiro Miyake, Hiroshi Matsushita, Atsuyuki Ohnishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY29 ( 1 ) 110 - 115   2014年1月

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

    Background and AimRecently, the association of the dysfunction of programmed cell death (PD)-1 expressed on activated lymphocytes with the pathogenesis of autoimmune hepatitis (AIH) has been speculated. This study aimed to investigate the association of serum anti-PD-1 antibodies with clinical characteristics of type 1 AIH.
    MethodsSerum samples before the initiation of prednisolone treatment were obtained from 52 type 1 AIH patients, 24 patients with drug-induced liver injury (DILI), 30 patients with acute viral hepatitis (AVH), 11 patients with primary sclerosing cholangitis (PSC), and 62 healthy volunteers. Titers of serum anti-PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay. The cutoff level was represented by a mean absorbance+2 standard deviations in healthy volunteers.
    ResultsPrevalence of serum anti-PD-1 antibodies was 63% in type 1 AIH patients, 8% in DILI patients, 13% in AVH patients, 18% in PSC patients, and 3% in healthy volunteers. In type 1 AIH patients, titers of serum anti-PD-1 antibodies were correlated with serum levels of bilirubin (r=0.31, P=0.030) and alanine aminotransferase (r=0.31, P=0.027) but not serum immunoglobulin G levels. Positivity for serum anti-PD-1 antibodies was associated with the later normalization of serum alanine aminotransferase levels after the initiation of prednisolone and the disease relapse.
    ConclusionsSerum anti-PD-1 antibodies would be useful for the discrimination of type 1 AIH from DILI, AVH, and PSC as an auxiliary diagnostic marker. Furthermore, anti-PD-1 antibodies may be associated with clinical characteristics of type 1 AIH.

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  • L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway 査読

    Hisashi Ishikawa, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY60 ( 7 ) 761A - 761A   2014年

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

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  • A case of Wilson's disease with characteristic laparoscopic findings 査読

    Shin-Ichiro Muro, Tetsuya Yasunaka, Nozomu Wada, Yuki Morimoto, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Kazuhiro Noso, Hiroaki Iwasaki, Kazuhide Yamamoto

    Clinical Journal of Gastroenterology7 ( 2 ) 175 - 179   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer-Verlag Tokyo  

    A 44-year-old male was pointed out liver function abnormality by medical check-up. Blood examination and computed tomography showed liver cirrhosis. Then, he was referred to our hospital for further examination. After blood test, viral markers revealed previous infection of hepatitis B virus (HBV). We estimated the etiology of his liver disease as previous HBV infection. On laparoscopic examination, his liver surface was nodular with mixed yellowish nodules and ash gray to copper-colored nodules in the diameter of 3-10 mm. There were large regenerative nodules in segments 3 and 4. Large regenerative nodules and irregular steatosis were contradictory to HBV-related liver cirrhosis, so then we supposed Wilson's disease. The amount of copper excretion in the urine was 326.6 μg (&gt
    100 μg/24 h). After D-penicillamine administration, urinary copper excretion increased to 2151.5 μg/24 h. Though hepatic copper concentration was 174.5 μg/g wet tissue (&gt
    200 μg/g wet tissue), his laboratory data fulfilled the Leipzig diagnostic criteria proposed by EASL. Laparoscopic examination with liver biopsy has advantages to survey many disease-specific findings on liver surface and to obtain adequate liver sample. Laparoscopic examination is one of the effective procedures for diagnosing relatively rare liver disease like Wilson's disease. © 2014 Springer.

    DOI: 10.1007/s12328-014-0465-7

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  • Which patients respond best to hepatitis B vaccination after a hepatitis B virus-related liver transplantation? 査読

    Akinobu Takaki, Takahito Yagi, Tetsuya Yasunaka, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Sato, Daisuke Nobuoka, Masashi Utsumi, Yuko Yasuda, Eiichi Nakayama, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Kazuhiro Nouso, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    Journal of Gastroenterology48 ( 12 ) 1373 - 1383   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: A combination of hepatitis B immunoglobulin and nucleos(t)ide analogues is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation (OLT). However, frequent immunoglobulin treatment is expensive and inconvenient. This study investigated the efficacy of hepatitis B virus (HBV) vaccination in preventing the recurrence of hepatitis B after living donor OLT. Methods: Twenty-seven patients who had undergone living donor OLT participated in the study
    five had acute HBV infected liver failure (ALF-OLT) and 22 had HBV related liver cirrhosis (LC-OLT). Hepatitis B surface antigen (HBsAg)-containing vaccine was administered to them for at least 1 year after transplantation and continued once monthly for up to 36 months post-OLT. Patients who had anti-HBs antibody titers above 100 mIU/mL for a minimum of 6 months without immunoglobulin administration were defined as good responders
    the others were defined as poor responders. Interferon-γ enzyme-linked immunospot assays against HBs and HBc antigens were used to assay cellular immune responses. Results: All five of the ALF-OLT patients had good responses after a median of four (range 2.5-5) vaccinations. Nine of the 22 LC-OLT patients had good responses after a median of 19 (range 11.5-30) vaccinations. Among the LC-OLT group, those with livers donated by relatively higher-aged, marital and high-titer anti-HBs antibody donors were good responders. LC-OLT patients classed as good responders showed interferon-γ responses comparable to those of the ALF-OLT patients. Conclusions: The ALF-OLT and LC-OLT patients who received livers from relatively higher-aged, marital, high-titer anti-HBs antibody donors were the best candidates for HBV vaccine administration. Boosting donors before transplantation may facilitate later vaccine response of the recipients. © 2013 The Author(s).

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  • Serum Glycan Markers for Evaluation of Disease Activity and Prediction of Clinical Course in Patients with Ulcerative Colitis 査読

    Koji Miyahara, Kazuhiro Nouso, Shunsuke Saito, Sakiko Hiraoka, Keita Harada, Sakuma Takahashi, Yuki Morimoto, Sayo Kobayashi, Fusao Ikeda, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Maho Amano, Kazuko Hirose, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    PLoS ONE8 ( 10 ) e74861   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background:The aims of this study were to determine the change of whole-serum N-glycan profile in ulcerative colitis (UC) patients and to investigate its clinical utility.Methods:We collected serum from 75 UC patients at the time of admission and the same number of age/sex-matched healthy volunteers. Serum glycan profile was measured by comprehensive quantitative high-throughput glycome analysis and was compared with disease activity and prognosis.Results:Out of 61 glycans detected, 24 were differentially expressed in UC patients. Pathway analysis demonstrated that highly sialylated multi-branched glycans and agalactosyl bi-antennary glycans were elevated in UC patients
    in addition, the glycan ratio m/z 2378/1914, which also increased in UC, showed the highest Area under Receiver Operating Characteristic curve (0.923) for the diagnosis of UC. Highly sialylated multi-branched glycans and the glycan ratio m/z 2378/1914 were higher in the patients with total colitis, Clinical Activity Index &gt
    10, Mayo endoscopic score 3, or a steroid-refractory status. In particular, the glycan ratio m/z 2378/1914 (above median) was an independent prognostic factor for the need for an operation (hazard ratio, 2.67
    95% confidence interval, 1.04-7.84).Conclusions:Whole-serum glycan profiles revealed that the glycan ratio m/z 2378/1914 and highly sialylated multi-branched glycans increase in UC patients, and are correlated with disease activity. The glycan ratio m/z 2378/1914 was an independent predictive factor of the prognosis of UC. © 2013 Miyahara et al.

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  • Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma. 査読

    Miyahara K, Nouso K, Morimoto Y, Takeuchi Y, Hagihara H, Kuwaki K, Onishi H, Ikeda F, Miyake Y, Nakamura S, Shiraha H, Takaki A, Honda M, Kaneko S, Sato T, Sato S, Obi S, Iwadou S, Kobayashi Y, Takaguchi K, Kariyama K, Takuma Y, Takabatake H, Yamamoto K, Okayama Liver, Cancer Group

    British journal of cancer109 ( 8 ) 2072 - 2078   2013年10月

  • Evaluation of the effect of sorafenib using serum NX-des-γ-carboxyprothrombin in patients with hepatocellular carcinoma. 査読

    Miyahara K, Nouso K, Morimoto Y, Tomoda T, Kobayashi S, Takeuchi Y, Hagihara H, Kuwaki K, Ohnishi H, Ikeda F, Miyake Y, Nakamura S, Shiraha H, Takaki A, Yamamoto K, Okayama Liver, Cancer Group

    Hepatology research : the official journal of the Japan Society of Hepatology43 ( 10 ) 1064 - 1070   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/hepr.12055

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  • Clinical utility of high-throughput glycome analysis in patients with pancreatic cancer 査読

    Kazuhiro Nouso, Maho Amano, Yoichi M. Ito, Koji Miyahara, Yuki Morimoto, Hironari Kato, Koichiro Tsutsumi, Takeshi Tomoda, Naoki Yamamoto, Shinichiro Nakamura, Sayo Kobayashi, Kenji Kuwaki, Hiroaki Hagihara, Hideki Onishi, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Taku Nakahara, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY48 ( 10 ) 1171 - 1179   2013年10月

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

    Most of the glycan changes reported in cancers were based on the examinations of a small number of patients or particular proteins. The aim of this study was to determine the changes of the serum N-glycan profile comprehensively in a large number of pancreatic cancer patients and investigate its clinical utility.
    Glycan levels in the serum of 92 pancreatic cancer patients and 243 healthy volunteers (HLT) were examined by comprehensive quantitative high-throughput glycome analysis and were compared with clinical parameters.
    Out of 66 glycans detected, 15 were differentially expressed in pancreatic cancer, and 10 out of the 15 glycans were significantly up-regulated in cases with distant metastasis. There was a clear increase in overall expression of serum glycans, especially highly-branched glycans with fucose moieties, in pancreatic cancer. Among these 15 glycans, a tri-antennary complex type glycan (m/z 3195) showed the highest area under the receiver operating characteristic curve (AUROC = 0.799) for the diagnosis of pancreatic cancer. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) was found to be significantly higher in pancreatic cancer than in HLT (median = 1.11 and 0.41, respectively; p < 0.0001, AUROC = 0.831). For this pair ratio, the hazard ratio for survival (2.60, 95 % CI = 1.44-4.79) was higher than that of any single glycan and 1-year survival of patients with a high and low ratio was 36.9 and 69.2 %, respectively, (p = 0.001).
    Comprehensive glycome analysis can be used to know the presence of pancreatic cancer, distant metastasis, and patient prognosis, simultaneously.

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  • Prognotic impact of serum follistatin in patients with hepatocellular carcinoma 査読

    Takeshi Tomoda, Kazuhiro Nouso, Koji Miyahara, Sayo Kobayashi, Hideaki Kinugasa, Junki Toyosawa, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Fusao Ikeda, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY28 ( 8 ) 1391 - 1396   2013年8月

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

    Background and Aim: Follistatin (FST) is a glycoprotein expressed in most organs, which interacts with activins or other members of the transforming growth factor beta family. Recently, several reports have shown that FST regulates a variety of processes during tumor progression. Here, serum FST in patients with liver diseases was measured, and its clinical utility as a biomarker was assessed.
    Methods: Serum was collected from 162 patients (91 hepatocellular carcinoma [HCC], 43 liver cirrhosis, and 28 chronic hepatitis) as well as from 16 healthy volunteers. FST was quantified by enzyme-linked immunosorbent assays, and levels were compared with clinical parameters including survival of the HCC patients.
    Results: Median serum FST levels in HCC, liver cirrhosis, chronic hepatitis, and healthy volunteers were 1168, 1606, 1324, and 1661 pg/mL, respectively, not significantly different. In HCC patients, higher serum FST was associated with greater age, hepatitis C virus antibody-negativity, large tumor size, g-glutamyl transpeptidase, des-gamma carboxyprothrombin and presence of portal vein tumor thrombus. Survival of HCC patients with high FST levels was significantly shorter than for those with low levels (P = 0.004). Multivariate analysis revealed that in addition to large tumor size and presence of portal vein thrombus, high FST levels were independently correlated with poor prognosis (hazard ratio = 2.41, 95% confidence interval = 1.16-5.00, P = 0.02).
    Conclusions: Serum FST levels are significantly associated with HCC prognosis and could represent a predictive biomarker in this disease.

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  • The Diagnosis of Hypovascular Hepatic Lesions Showing Hypo-intensity in the Hepatobiliary Phase of Gd-EOB-DTPA-enhanced MR Imaging in High-risk Patients for Hepatocellular Carcinoma 査読

    Shinichiro Nakamura, Kazuhiro Nouso, Yoshiyuki Kobayashi, Hidenori Shiraha, Hideki Ohnishi, Junichi Toshimori, Kenji Kuwaki, Hiroaki Hagihara, Hiroki Takayama, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA67 ( 4 ) 239 - 244   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    The aim of this study was to evaluate the histologic diagnosis of hypovascular hepatic lesions showing hypointensity on hepatobiliary phase images of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI (EOB-MRI). In 38 patients with hepatocellular carcinoma (HCC) after curative treatments and 18 patients with liver cirrhosis, 105 hypovascular nodules that were hypointense at the hepatobiliary phase of EOB-MRI were biopsied and the clinical usefulness of these EOB-MRI findings for the diagnosis of HCC was examined. Of the 105 nodules (median diameter = 12 nun), 78 (74.3%), 11(10.5%), and 16 (15.2%) were diagnosed as HCC, dysplastic, and non-neoplastic, respectively. The positive predictive value (PPV) of hypointensity at the hepatobiliary phase of EOB-MRI for the diagnosis of HCC increased to 77-90% when combined with the following factors: washout appearance on the delayed phase of triple-phase CT, hyperintensity in diffusion-weighted image of MRI, or the appearance of a hypoechoic part in ultrasonography. PPV increased to 100% when all 3 factors were positive. A relatively large proportion of hypovascular lesions that showed hypo-intensity in the hepatobiliary phase were confirmed to be HCC, and the accuracy of HCC increased when combined with other imaging findings.

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  • Human hepatocyte carcinogenesis (Review) 査読

    Hidenori Shiraha, Kazuhide Yamamoto, Masayoshi Namba

    INTERNATIONAL JOURNAL OF ONCOLOGY42 ( 4 ) 1133 - 1138   2013年4月

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

    Hepatocellular carcinoma is the third most frequent cause of cancer-related death worldwide; and its incidence rate is increasing. Clinical and molecular medical analyses have revealed substantial information on hepatocarcinogenesis. Hepatocarcinogenesis is a stepwise process during which multiple genes are altered. Genetic changes and their biological consequences in human HCC can be divided into at least 4 groups: i) tumor suppressor genes (p53, retinoblastoma, phosphatase tensin homolog and runt-related transcription factor 3), ii) oncogenes (myc, K-ras, BRAF), iii) reactivation of developmental pathways (Wnt, hedgehog), and iv) growth factors and their receptors (transforming growth factor-a, insulin-like growth factor-2 receptor). An experimental model of human hepatocarcinogenesis such as in vitro neoplastic transformation of human hepatocytes has not been successfully achieved yet, but several immortalized human hepatocyte cell lines have been established. These immortalized human hepatocytes will become useful tools for the elucidation of hepatocarcinogenesis, especially for the initial step of multistep hepatocarcinogenesis.

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  • The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis 査読

    Yasuto Takeuchi, Fusao Ikeda, Yuki Moritou, Hiroaki Hagihara, Tetsuya Yasunaka, Kenji Kuwaki, Yasuhiro Miyake, Hideki Ohnishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Yoshiaki Iwasaki, Kazuhiro Nouso, Kazuhide Yamamoto

    Journal of Gastroenterology48 ( 3 ) 405 - 412   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background The single nucleotide polymorphism (SNP) rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat accumulation and disease progression in patients with nonalcoholic fatty liver disease and alcoholic liver disease (ALD). This study was conducted to determine whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular carcinoma (HCC) in patients with various liver diseases. Methods We enrolled 638 consecutive Japanese patients newly diagnosed with HCC between 2001 and 2010: 72 patients with hepatitis B virus (HBV), 462 with hepatitis C virus (HCV), and 104 with non-B non-C (NBNC). Results NBNC patients exhibited large tumors of advanced TNM stages at HCC diagnosis, and had significantly poorer prognosis than HBV or HCV patients (P&lt
    0.001 and &lt
    0.001, respectively
    log-rank test). The G/G genotype of PNPLA3 rs738409 SNP had significantly higher distribution in NBNC patients (P&lt
    0.001) and was significantly associated with higher body mass index (BMI) and an increased aspartate aminotransferase to platelet ratio index. No significant differences were observed in survival with differences in PNPLA3 SNP genotypes among the patients, although ALD patients with the G/G genotype of PNPLA3 SNP and low BMI had significantly poorer survival than those with high BMI (P = 0.028). Conclusions The G/G genotype of PNPLA3 rs738409 SNP was more frequently distributed, and associated with BMI and fibrosis among NBNC-HCC patients but not among HBV or HCV patients. These genotypes might affect HCC prognosis in ALD patients, but not in HBV, HCV, or NAFLD patients. © Springer 2012.

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  • Loss of runt-related transcription factor 3 induces gemcitabine resistance in pancreatic cancer 査読

    Shigeru Horiguchi, Hidenori Shiraha, Teruya Nagahara, Jyunnro Kataoka, Masaya Iwamuro, Minoru Matsubara, Shinichi Nishina, Hironari Kato, Akinobu Takaki, Kazuhiro Nouso, Takehiro Tanaka, Koichi Ichimura, Takahito Yagi, Kazuhide Yamamoto

    Molecular Oncology7 ( 4 ) 840 - 849   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:John Wiley and Sons Ltd  

    Background &amp
    Aim: Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene that is expressed in gastric and other cancers including pancreatic cancer. However, the precise function of RUNX3 in pancreatic cancer has not been fully elucidated. In this study, we aimed to determine the effect of decreased RUNX3 expression in pancreatic cancer. Methods: This study included 36 patients with primary pancreatic cancer, who had undergone pancreaticoduodenectomy. All patients were treated with 1000mg/m2 gemcitabine after the surgery. The pancreatic cancer cell lines PANC-1, MIAPaCa-2, BxPC-3, SUIT-2, and KLM-1 were used for immunoblotting analysis of RUNX3 and multidrug resistance protein (MRP) expressions. Ectopic RUNX3 expression was achieved by cDNA transfection of the cells, and small interfering RNA (siRNA) against RUNX3 was used to knock down endogenous RUNX3. Cell growth in the presence of gemcitabine was assessed using the MTT assay. Results: Patients with RUNX3-positive and RUNX3-negative pancreatic cancer had a median survival of 1006 and 643 days, respectively. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, and MRP5 in endogenous RUNX3-negative cells, whereas RUNX3 siRNA increased the expressions of these genes in endogenous RUNX3-positive cells. Exogenous RUNX3 expression decreased gemcitabine IC50 in RUNX3-negative cells. Conclusion: Loss of RUNX3 expression contributes to gemcitabine resistance by inducing MRP expression, thereby resulting in poor patient survival. © 2013 Federation of European Biochemical Societies.

    DOI: 10.1016/j.molonc.2013.04.004

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  • Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma 査読

    Shigetomi Tanaka, Hidenori Shiraha, Yutaka Nakanishi, Shin-Ichi Nishina, Minoru Matsubara, Shigeru Horiguchi, Nobuyuki Takaoka, Masaya Iwamuro, Junro Kataoka, Kenji Kuwaki, Hiroaki Hagihara, Junichi Toshimori, Hideki Ohnishi, Akinobu Takaki, Shinichiro Nakamura, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto

    INTERNATIONAL JOURNAL OF CANCER131 ( 11 ) 2537 - 2546   2012年12月

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

    Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelialmesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low- and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased E-cadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low- and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC.

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  • Eradication of Hepatitis C Virus Subgenomic Replicon by Interferon Results in Aberrant Retinol-Related Protein Expression 査読

    Kazuko Koike, Akinobu Takaki, Nobuyuki Kato, Mamoru Ouchida, Hirotaka Kanzaki, Tetsuya Yasunaka, Hidenori Shiraha, Yasuhiro Miyake, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA66 ( 6 ) 461 - 468   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Hepatitis C virus (HOT) infection induces several changes in hepatocytes, such as oxidative stress, steatosis, and hepatocarcinogenesis. Although considerable progress has been made during recent years, the mechanisms underlying these functions remain unclear. We employed proteomic techniques in HCV replicon-harboring cells to determine the effects of HCV replication on host-cell protein expression. We examined two-dimensional electrophoresis (2-DE) and mass spectrometry to compare and identify differentially expressed proteins between HCV subgenomic replicon-harboring cells and their "cured" cells. One of the identified proteins was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Full-length HCV genome RNA replicating and cured cells were also assessed using ELISA. Replicon-harboring cells showed higher expression of retinal dehydrogenase 1 (RALDH-1), which converts retinol to retinoic acid, and the cured cells showed higher expression of retinol-binding protein (RBP), which transports retinol from the liver to target tissues. The alteration in RBP expression was also confirmed by ELISA and Western blot analysis. We conclude that protein expression profiling demonstrated that HCV replicon eradication affected retinol-related protein expression.

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  • A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes 査読

    Masaya Iwamuro, Hidenori Shiraha, Shuhei Nakaji, Masumi Furutani, Naoya Kobayashi, Akinobu Takaki, Kazuhide Yamamoto

    BIOMEDICAL ENGINEERING ONLINE11   93   2012年12月

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

    Background: Bioartificial liver systems, designed to support patients with liver failure, are composed of bioreactors and functional hepatocytes. Immunological rejection of the embedded hepatocytes by the host immune system is a serious concern that crucially degrades the performance of the device. Induced pluripotent stem (iPS) cells are considered a desirable source for bioartificial liver systems, because patient-derived iPS cells are free from immunological rejection. The purpose of this paper was to test the feasibility of a bioartificial liver system with iPS cell-derived hepatocyte-like cells.
    Methods: Mouse iPS cells were differentiated into hepatocyte-like cells by a multi-step differentiation protocol via embryoid bodies and definitive endoderm. Differentiation of iPS cells was evaluated by morphology, PCR assay, and functional assays. iPS cell-derived hepatocyte-like cells were cultured in a bioreactor module with a pore size of 0.2 mu m for 7 days. The amount of albumin secreted into the circulating medium was analyzed by ELISA. Additionally, after a 7-day culture in a bioreactor module, cells were observed by a scanning electron microscope.
    Results: At the final stage of the differentiation program, iPS cells changed their morphology to a polygonal shape with two nucleoli and enriched cytoplasmic granules. Transmission electron microscope analysis revealed their polygonal shape, glycogen deposition in the cytoplasm, microvilli on their surfaces, and a duct-like arrangement. PCR analysis showed increased expression of albumin mRNA over the course of the differentiation program. Albumin and urea production was also observed. iPS-Heps culture in bioreactor modules showed the accumulation of albumin in the medium for up to 7 days. Scanning electron microscopy revealed the attachment of cell clusters to the hollow fibers of the module. These results indicated that iPS cells were differentiated into hepatocyte-like cells after culture for 7 days in a bioreactor module with a pore size of 0.2 mu m.
    Conclusion: We consider the combination of a bioreactor module with a 0.2-mu m pore membrane and embedded hepatocytes differentiated from iPS cells to be a promising option for bioartificial liver systems. This paper provides the basic concept and preliminary data for an iPS cell-oriented bioartificial liver system. PACS code: 87. Biological and medical physics, 87.85.-d Biomedical engineering, 87.85.Lf Tissue engineering, 87.85.Tu Modeling biomedical systems.

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  • Clinical utility of serum fucosylated hemopexin in Japanese patients with hepatocellular carcinoma 査読

    Sayo Kobayashi, Kazuhiro Nouso, Hideaki Kinugasa, Yasuto Takeuchi, Takeshi Tomoda, Koji Miyahara, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Fusao Ikeda, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH42 ( 12 ) 1187 - 1195   2012年12月

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

    Aim: Hepatocellular carcinoma (HCC) is a common clinical problem all over the world. Fucosylated hemopexin (Fuc-Hpx) is a newly reported glycoprotein for the diagnosis of HCC, however, its clinical implications are unclear. The aim of this study was to elucidate the clinical utility of Fuc-Hpx in Japanese patients with HCC.
    Methods: The sera from 331 HCC patients, 45 with liver cirrhosis (LC), 85 with chronic hepatitis (CH) and 22 healthy people were examined for the expression of Fuc-Hpx; the level was compared with clinical parameters as well as hemopexin (Hpx) expression. The expressions of Fuc-Hpx in 12 HCC tissues and corresponding adjacent non-cancerous liver tissues were also examined.
    Results: No correlation was observed between Hpx and Fuc-Hpx level. The median Fuc-Hpx levels in healthy people and CH, LC and HCC patients were 3.8, 3.7, 6.1 and 7.6 AU/mL, respectively (CH vs LC, P = 0.002; CH vs HCC, P < 0.001; LC vs HCC, P = 0.02). Multivariate analysis revealed that low albumin, low prothrombin time and the presence of HCC were significantly correlated with high Fuc-Hpx (P = 0.013, =0.001 and <0.001, respectively). Among the HCC patients, albumin was correlated with high Fuc-Hpx; however, none of the tumor factors, such as tumor size, tumor number and tumor stage, was correlated with Fuc-Hpx level. The expression of Fuc-Hpx in cancer tissue was not different from that in non-cancerous tissue.
    Conclusion: Fuc-Hpx is a valuable biomarker for HCC but it might be a marker for hypercarcinogenic liver rather than a marker for tumor-bearing liver.

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  • Des-γ-carboxyl prothrombin is associated with tumor angiogenesis in hepatocellular carcinoma. 査読

    Matsubara M, Shiraha H, Kataoka J, Iwamuro M, Horiguchi S, Nishina S, Takaoka N, Uemura M, Takaki A, Nakamura S, Kobayashi Y, Nouso K, Yamamoto K

    Journal of gastroenterology and hepatology27 ( 10 ) 1602 - 1608   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice 査読

    Daisuke Kawai, Akinobu Takaki, Atsuko Nakatsuka, Jun Wada, Naofumi Tamaki, Tetsuya Yasunaka, Kazuko Koike, Ryuichiro Tsuzaki, Kazuyuki Matsumoto, Yasuhiro Miyake, Hidenori Shiraha, Manabu Morita, Hirofumi Makino, Kazuhide Yamamoto

    HEPATOLOGY56 ( 3 ) 912 - 921   2012年9月

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

    Oxidative stress is a strong contributor to the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). Molecular hydrogen is an effective antioxidant that reduces cytotoxic reactive oxygen species. In this study, we investigated the effects of hydrogen-rich water and the drug pioglitazone on the progression of NASH in mouse models. A methionine-cholinedeficient (MCD) diet mouse model was prepared. Mice were divided into three experimental groups and fed for 8 weeks as follows: (1) MCD diet + control water (CW group); (2) MCD diet + hydrogen-rich water (HW group); and (3) MCD diet mixed with pioglitazone (PGZ group). Plasma alanine aminotransferase levels, hepatic expression of tumor necrosis factor-a, interleukin-6, fatty acid synthesisrelated genes, oxidative stress biomarker 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis marker terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick-end labeling (TUNEL)positive cells in the liver were decreased in the HW and PGZ groups. The HW group showed a smaller decrease in hepatic cholesterol; however, stronger antioxidative effects in serum and lower peroxisome proliferator-activated receptor-a expression in the liver were seen in comparison with the PGZ group. We then investigated the effects of hydrogen in the prevention of hepatocarcinogenesis in STAM mice, known as the NASH-related hepatocarcinogenesis model. Eight-week-old male STAM mice were divided into three experimental groups as follows: (1) control water (CW-STAM); (2) hydrogen-rich water (HW-STAM); and (3) pioglitazone (PGZ-STAM). After 8 weeks, hepatic tumors were evaluated. The number of tumors was significantly lower in the HW-STAM and PGZ-STAM groups than in the CW-STAM group. The maximum tumor size was smaller in the HW-STAM group than in the other groups. Conclusion: Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis. (HEPATOLOGY 2012;56:912921)

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  • Diagnostic usefulness of precise examinations with intraductal ultrasonography, peroral cholangioscopy and laparoscopy of immunoglobulin G4-related sclerosing cholangitis 査読

    Shigeru Horiguchi, Fusao Ikeda, Hidenori Shiraha, Naoki Yamamoto, Ichiro Sakakihara, Yasuhiro Noma, Koichiro Tsutsumi, Hironari Kato, Hiroaki Hagihara, Tetsuya Yasunaka, Shinichiro Nakamura, Haruhiko Kobashi, Hirofumi Kawamoto, Kazuhide Yamamoto

    DIGESTIVE ENDOSCOPY24 ( 5 ) 370 - 373   2012年9月

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

    Herein, a case of immunoglobulin G4 (IgG4)-related sclerosing cholangitis is reported. IgG4 was diagnosed based on observations from peroral cholangioscopy and laparoscopy, and these methods are proposed for definitive and precise diagnosis of this disease. A 76-year-old male patient with inguinal Paget's disease had intrahepatic bile duct dilatations detected with computed tomography at his periodic check-up. Magnetic resonance cholangiography showed stenosis of the upper common bile duct and poststenotic dilatation of left intrahepatic bile ducts. The portal tract and bilateral intrahepatic bile ducts were surrounded by a low-density area, facing a tumor-like lesion at segment 2. Cytological examinations of the stenotic and dilated lesions revealed no cellular atypia. Histological examination of the tumor showed normal liver tissue with infiltration of lymphocytes, indicating an inflammatory pseudotumor. Peroral cholangioscopy excluded the possibility of biliary cancer and indicated that the stenotic legion was of submucosal, not mucosal, origin. Laparoscopic observations showed discoloration with wide yellowish-white lobular markings and wide depressed lesions at segments 2 and 7. Liver histology showed mild cholangitis with infiltration of IgG4-positive plasma cells around the bile ducts. Serum IgG4 levels were elevated. From these findings, the patient was diagnosed with IgG4-related sclerosing cholangitis. After treatment with prednisolone, blood liver enzymes and IgG4 rapidly normalized, bile duct dilatations improved, and the hepatic pseudotumor disappeared. The cholangitis did not recur. In this case, biliary cancer was ruled out by observation with peroral cholangioscopy, and the spread of cholangitis in the liver periphery was verified with laparoscopy; this information could not be obtained with other modalities.

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  • Risk factors for recurrence after transarterial chemoembolization for early-stage hepatocellular carcinoma 査読

    Hideaki Kinugasa, Kazuhiro Nouso, Yasuto Takeuchi, Tetsuya Yasunaka, Hideki Onishi, Shin-ichiro Nakamura, Hidenori Shiraha, Kenji Kuwaki, Hiroaki Hagihara, Fusao Ikeda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY47 ( 4 ) 421 - 426   2012年4月

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

    Radiofrequency ablation (RFA) is a standard therapy for the treatment of hepatocellular carcinoma (HCC) with 3 or fewer tumors of up to 3 cm (early-stage HCC); when RFA is unsuccessful or unfeasible, transcatheter arterial chemoembolization (TACE) has often been performed. However, little information about the outcome of TACE for early-stage HCC has been reported and it is hard to decide whether to perform additional treatment following TACE in these difficult conditions. The aim of this study was to determine the risk factors for local or intrahepatic distant recurrence after TACE in early-stage HCC.
    Among 1,560 newly diagnosed HCC patients who were admitted to Okayama University Hospital, 43 patients with early-stage HCC who received only TACE in at least one nodule were enrolled in this study. We analyzed the risk factors for local and distant recurrence by the Cox proportional hazard model.
    The local recurrence rates and intrahepatic distant recurrence rates at 3 months, 6 months, and 1 year were 18.6, 33.4, and 61.8%, and 2.8, 2.8, and 10.2%, respectively. Among 12 parameters examined as possible risk factors for recurrence, heterogeneous Lipiodol uptake (risk ratio 3.38; 95% confidence interval 1.14-10.60) and high serum des-gamma-carboxy prothrombin (DCP) (2.58; 1.03-7.14) were significantly correlated with local recurrence, and the presence of multiple tumors (10.64; 1.76-93.75) was significantly correlated with intrahepatic distant recurrence.
    Heterogeneous Lipiodol uptake, high serum DCP, and multiple tumors are risk factors for recurrence in patients with early-stage HCC who have undergone palliative TACE.

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  • Erratum: Risk factors for recurrence after transarterial chemoembolization for early-stage hepatocellular carcinoma (Journal of Gastroenterology (2012) DOI: 10.1007/s00535-011-0492-9) 査読

    Hideaki Kinugasa, Kazuhiro Nouso, Yasuto Takeuchi, Tetsuya Yasunaka, Hideki Onishi, Shin-Ichiro Nakamura, Hidenori Shiraha, Kenji Kuwaki, Hiroaki Hagihara, Fusao Ikeda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto

    Journal of Gastroenterology47 ( 4 ) 489   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00535-011-0508-5

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  • Pancreatic Involvement in 11 Cases of Von Hippel-Lindau Disease 査読

    Masaya Iwamuro, Hirofumi Kawamoto, Hidenori Shiraha, Soichiro Nose, Kazuhide Yamamoto

    HEPATO-GASTROENTEROLOGY59 ( 114 ) 589 - 591   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBLISHING S A  

    Background/Aims: Von Hippel-Lindau disease is an autosomal dominant genetic disorder characterized by neoplasms developing in multiple organs. Although the pancreas is one of the most frequently involved organs, the frequency of pancreatic cysts, cystadenomas, neuroendocrine tumors and diabetes has not been sufficiently evaluated clue to the low prevalence of this disease. In this paper, we review and retrospectively analyze 11 patients with von Hippel-Lindau disease. Methodology: Eleven patients (6 males, 5 females) who underwent CT or MRI scans at Okayama University Hospital between 2002 and 2009 were enrolled in this study. Their pancreatic CT scans, MRI scans, biochemical test results and clinical histories were retrospectively reviewed. Results: All patients had one or more pancreatic involvements. Nine of the 11 patients had multiple pancreatic cysts, 2 had dilatation of the main pancreatic duct, 3 had a non-functioning pancreatic endocrine tumor (one patient required pancreatoduodenectomy due to the endocrine carcinoma) and 3 had diabetes mellitus. Pancreatic cystadenomas were not detected in this case series. Conclusions: The prevalence of pancreatic involvement was 100% in this study. Regular screening and scheduled follow-up for pancreatic lesions and diabetes should be performed on individuals predisposed to von Hippel-Lindau disease.

    DOI: 10.5754/hge10236

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  • Serum Levels of Soluble Adhesion Molecules as Prognostic Factors for Acute Liver Failure 査読

    Atsuyuki Ohnishi, Yasuhiro Miyake, Hiroshi Matsushita, Kazuyuki Matsumoto, Akinobu Takaki, Tetsuya Yasunaka, Kazuko Koike, Fusao Ikeda, Hidenori Shiraha, Kazuhiro Nouso, Kazuhide Yamamoto

    DIGESTION86 ( 2 ) 122 - 128   2012年

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

    Background/Aims: In patients with septic shock, the degree of liver dysfunction is correlated with serum levels of soluble intercellular adhesion molecule (sICAM)-1. We aimed to assess the usefulness of serum levels of soluble adhesion molecules as prognostic factors for acute liver failure (ALF). Methods: Serum levels of soluble platelet endothelial cell adhesion molecule (sPECAM)-1, sICAM-3, soluble endothelial (sE) selectin, sICAM-1, soluble platelet selectin, and soluble vascular cell adhesion molecule-1 on admission were measured in 37 ALF patients and 34 healthy controls. Results: Twenty-two ALF patients (59%) reached to fatal outcomes. Serum levels of sPECAM-1, sICAM-3, sE-selectin and sICAM-1 were higher in ALF patients than healthy controls. In 37 ALF patients, by the multivariate logistic regression analysis, ratio of direct to total bilirubin (per 0.1 increase; OR 0.11, 95% CI 0.01-0.99), serum sPECAM-1 level (per 100 ng/ml increase; OR 4.37, 95% CI 1.23-15.5) and serum sICAM-1 level (per 100 ng/ml increase; OR 0.49, 95% CI 0.27-0.89) were associated with fatal outcomes. Using receiver operating characteristics curve, each area under the curve of serum sPECAM-1 and sICMA-1 levels as prognostic factors was 0.71 and 0.74, respectively. Conclusion: Serum sPECAM-1 and sICAM-1 levels may be useful for predicting the prognosis of ALF. Copyright (c) 2012 S. Karger AG, Basel

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  • Serum hepatitis B virus DNA before liver transplantation correlates with HBV reinfection rate even under successful low-dose hepatitis B immunoglobulin prophylaxis 査読

    Tetsuya Yasunaka, Akinobu Takaki, Takahito Yagi, Yoshiaki Iwasaki, Hiroshi Sadamori, Kazuko Koike, Satoshi Hirohata, Masashi Tatsukawa, Daisuke Kawai, Hidenori Shiraha, Yasuhiro Miyake, Fusao Ikeda, Haruhiko Kobashi, Hiroaki Matsuda, Susumu Shinoura, Ryuichi Yoshida, Daisuke Satoh, Masashi Utsumi, Teppei Onishi, Kazuhide Yamamoto

    HEPATOLOGY INTERNATIONAL5 ( 4 ) 918 - 926   2011年12月

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

    Purpose The combination of hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogues has been accepted as the best treatment to control hepatitis B recurrence after orthotopic liver transplantation (OLT). However, the optimal dose of HBIg remains unclear. We have previously reported that high-dose HBIg in the early period followed by low-dose HBIg with nucleos(t)ide analogues offers reliable and cost-effective control of hepatitis B recurrence. The aim of this study was to investigate intrahepatic hepatitis B virus (HBV) reinfection status with our clinically successful protocol.
    Methods We quantified levels of intrahepatic HBV covalently closed circular (ccc) deoxyribonucleic acid (DNA) and serum hepatitis B core-related antigen (HBcrAg), a new serological marker that can estimate intrahepatic cccDNA levels. Nucleos(t)ide analogues were administered in all cases.
    Results No patients showed recurrence of hepatitis B surface antigen (HBsAg) or HBV-DNA. However, HBV, cccDNA, and HBcrAg were positive in 57% and 48% of patients after OLT, respectively. Pre-OLT serum HBV-DNA and HBcrAg levels correlated linearly with post-OLT cccDNA levels (r = 0.534, P < 0.05, and r = 0.634, P < 0.05, respectively). High serum HBV-DNA and HBcrAg levels, particularly with > 3 log(10) copies/mL and > 4 log(10) IU/mL, respectively, at the time of OLT, were associated with high levels of post-OLT cccDNA. Even with our successful protocol, nearly half of patients showed HBV reinfection.
    Conclusions Patients with high serum HBV-DNA and HBcrAg levels before OLT (particularly > 3 log(10) copies/mL and > 4 log(10) IU/mL, respectively) should be followed with care for HBV recurrence.

    DOI: 10.1007/s12072-011-9265-z

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  • Predicting the treatment effect of sorafenib using serum angiogenesis markers in patients with hepatocellular carcinoma 査読

    Koji Miyahara, Kazuhiro Nouso, Takeshi Tomoda, Sayo Kobayashi, Hiroaki Hagihara, Kenji Kuwaki, Junichi Toshimori, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY26 ( 11 ) 1604 - 1611   2011年11月

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

    Background and Aim: Sorafenib, the first agent demonstrated to have efficacy to improve the survival of patients with advanced hepatocellular carcinoma (HCC), is an active multikinase inhibitor affecting angiogenesis and tumor proliferation. We analyzed cytokines related to angiogenesis or cell proliferation, and tried to determine their utility as biomarkers of sorafenib treatment effect for HCC.
    Methods: Nine serum cytokines (angiopoietin-2 [Ang-2], follistatin, granulocyte colony-stimulating factor [G-CSF], hepatocyte growth factor [HGF], interleukin-8 [IL-8], leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor) were measured in 30 HCC patients treated with sorafenib, and the effects of treatment were compared using modified Response Evaluation Criteria in Solid Tumors.
    Results: All but IL-8 were significantly higher at baseline in patients with progressive disease. Progression-free survival was significantly shorter in patients with high levels of Ang-2, G-CSF, HGF, and leptin, and the hazard ratios were 2.51, 6.89, 2.55, and 4.14, respectively. As the number of cytokines at a high level increased, the treatment response deteriorated. Disease progression was seen in three of 12 (25.0%) patients with zero to two high biomarkers, two of six (33.3%) patients with 3-5 high biomarkers, and 10 of 12 (83.3%) patients with six to eight high biomarkers (P = 0.008). The prognosis of all patients with eight high biomarkers was progressive disease.
    Conclusion: High levels of serum cytokines at baseline were correlated with poor effects of sorafenib treatment in patients with HCC.

    DOI: 10.1111/j.1440-1746.2011.06887.x

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  • Hepatitis B virus core promoter mutations G1613A and C1653T are significantly associated with hepatocellular carcinoma in genotype C HBV-infected patients 査読

    Masashi Tatsukawa, Akinobu Takaki, Hidenori Shiraha, Kazuko Koike, Yoshiaki Iwasaki, Haruhiko Kobashi, Shin-Ichi Fujioka, Kohsaku Sakaguchi, Kazuhide Yamamoto

    BMC CANCER11   458   2011年10月

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

    Background: Hepatitis B virus (HBV) is a major cause of hepatocarcinogenesis. To identify mutations relevant to hepatocellular carcinoma (HCC) development, we compared the full genome sequences of HBV from the sera of patients with and without HCC.
    Methods: We compared the full genome sequences of HBV isolates from 37 HCC patients (HCC group 1) and 38 patients without HCC (non-HCC group 1). We also investigated part of the core promoter region sequences from 40 HCC patients (HCC group 2) and 68 patients without HCC. Of the 68 patients who initially did not have HCC, 52 patients remained HCC-free during the follow-up period (non-HCC group 2), and 16 patients eventually developed HCC (pre-HCC group 2). Serum samples collected from patients were subjected to PCR, and the HBV DNA was directly sequenced.
    Results: All patients had genotype C. A comparison of the nucleotide sequences of the HBV genome between HCC group 1 and non-HCC group 1 revealed that the prevalence of G1613A and C1653T mutations in the core promoter region was significantly higher in the HCC group. These mutations tended to occur simultaneously in HCC patients. Multivariate analysis with group 2 revealed that the presence of HCC was associated with aging and the double mutation. Future emergence of HCC was associated with aging and the presence of a single G1613A mutation.
    Conclusions: G1613A and C1653T double mutations were frequently found in patients with HCC. A single G1613A mutation was associated with future emergence of HCC. These mutations may serve as useful markers in predicting HCC development.

    DOI: 10.1186/1471-2407-11-458

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  • Restored expression of the tumor suppressor gene RUNX3 reduces cancer stem cells in hepatocellular carcinoma by suppressing Jagged1-Notch signaling 査読

    Shin-Ichi Nishina, Hidenori Shiraha, Yutaka Nakanishi, Shigetomi Tanaka, Minoru Matsubara, Nobuyuki Takaoka, Masayuki Uemura, Shigeru Horiguchi, Junro Kataoka, Masaya Iwamuro, Takahito Yagi, Kazuhide Yamamoto

    ONCOLOGY REPORTS26 ( 3 ) 523 - 531   2011年9月

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

    Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene that is downregulated in various cancers. In the present study, we analyzed the regulatory function of RUNX3 on Jagged-1 (JAG1) expression and cancer stem cell (CSC) signaling in hepatocellular carcinoma (HCC). Eleven HCC cell lines and 30 human HCC tissues were used. RUNX3 and JAG1 expression levels were analyzed by immunoblotting and immunohistochemistry. Ectopic RUNX3 expression was induced by introducing RUNX3 cDNA into the RUNX3-negative HCC cell line Hep3B and Huh7 cells. Furthermore endogenous RUNX3 expression was knocked down by RUNX3 siRNA in SK-Hep-1 cells. In order to analyze JAG1 transcriptional regulation, we conducted reporter assays, chromatin immunoprecipitation (ChIP) assays and electrophoretic mobility shift assays (EMSAs). Tumorigenicity was analyzed using a SCID mouse liver injection model. An inverse correlation was observed between RUNX3 expression and JAG1 expression in most HCC cell lines and tissues. Restoring RUNX3 expression decreased the expression of JAG1 in Hep3B and Huh7 cells, whereas JAG1 expression was upregulated in RUNX3 siRNA-treated SK-Hep-1 cells. Reporter assays, ChIP assays and EMSAs revealed that RUNX3 directly bound to the transcriptional regulatory region of JAG1 and suppressed JAG1 transcription. Moreover, RUNX3 restoration downregulated CSCs by suppressing JAG1-mediated Notch signaling. The tumorigenic capacity of RUNX3-expressing Hep3B cells was lower compared to that of control Hep3B cells. RUNX3 expression suppressed JAG1 expression and resulted in downregulation of tumorigenesis by suppression of JAG1-mediated CSCs.

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  • Prognostic importance of fucosylated alpha-fetoprotein in hepatocellular carcinoma patients with low alpha-fetoprotein 査読

    Kazuhiro Nouso, Yoshiyuki Kobayashi, Shinichiro Nakamura, Sayo Kobayashi, Hiroki Takayama, Junichi Toshimori, Kenji Kuwaki, Hiroaki Hagihara, Hideki Onishi, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Yoshiaki Iwasaki, Haruhiko Kobashi, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY26 ( 7 ) 1195 - 1200   2011年7月

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

    Background and Aim: Fucosylated alpha-fetoprotein (AFP-L3) is known to be a marker of poor prognosis in patients with hepatocellular carcinoma (HCC). However, it has been difficult to measure AFP-L3 under low AFP (<= 20 ng/mL). The aim of this study was to elucidate the role of AFP-L3 in HCC patients with low AFP conditions.
    Methods: One hundred and ninety six consecutive newly developed HCC patients with low AFP (<= 20 ng/mL) were examined for serum AFP-L3 expression by a newly-developed micro-total analysis system that could stably measure AFP-L3 in low AFP circumstances, and its clinical importance was analyzed.
    Results: Positivity of AFP-L3 in HCC patients was 13.3% at a cut-off level of 10%. Five-year survivals of HCC patients with AFP-L3 (< 10%) and AFP-L3 (>= 10%) were 69.4% and 41.1%, respectively (P = 0.001). Among 18 clinical parameters, low alanine aminotransferase, large tumor size, presence of portal vein tumor thrombus, high AFP and high des-gamma carboxy prothrombin were observed in the high AFP-L3 (>= 10%) group. Multivariate analysis revealed that high aspartate aminotransferase (AST) (risk ratio [RR] = 3.24, 95% confidence interval [Cl] = 1.27-8.26), the presence of ascites (RR = 3.44, 95% Cl = 1.22-9.34), multiple tumor number (RR = 3.06, 95% CI = 1.33-7.17), and high AFP-L3 (RR = 8.36, 95% Cl = 2.79-25.5) were risk factors for survival. High AFP-L3 was also a risk factor for survival in HCC patients who received radiofrequency ablation (P = 0.048).
    Conclusions: AFP-L3 is a strong prognostic factor for survival even in HCC patients with low AFP (<= 20 ng/mL).

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  • Effect of pegylated interferon therapy on intrahepatic recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma 査読

    Hiroaki Hagihara, Kazuhiro Nouso, Yoshiyuki Kobayashi, Yoshiaki Iwasaki, Shinichiro Nakamura, Kenji Kuwaki, Junichi Toshimori, Hirokazu Miyatake, Hideki Ohnishi, Hidenori Shiraha, Kazuhide Yamamoto

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY16 ( 3 ) 210 - 220   2011年6月

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

    We wished to determine whether pegylated interferon (PEG-IFN) therapy after curative treatment of hepatocellular carcinoma (HCC) prevents a recurrence of HCC.
    Thirty-seven HCC patients with hepatitis C virus (HCV) infection who were treated with PEG-IFN after curative treatment (PEG-IFN group) and 145 controls without IFN therapy (non-IFN group) were enrolled. The overall survival and recurrence-free survival rates were compared between the groups, and the predisposing factors for recurrence and survival were analyzed. The rates were also examined by propensity score (PS) matched analysis that could minimize selection biases.
    The median follow-up period was 3.7 years. The 5-year survival rate in the PEG-IFN group (91%) was significantly higher than that in the non-IFN group (56%; P < 0.01). The rate of the second recurrence but not that of the first recurrence of HCC in the sustained virological responder (SVR) group was lower than that in the non-IFN group (P = 0.03). Improvement of survival by PEG-IFN and low rate of second recurrence in the SVR group were also observed in PS matched analysis. Multivariate analysis revealed that PEG-IFN therapy and high serum albumin were good prognostic factors for survival. Although low serum albumin and large and multiple tumors were risk factors for the first recurrence, non-SVR and low serum albumin were risk factors for the second recurrence.
    PEG-IFN-therapy after curative treatment of HCC improved the rate of survival, and SVR was found to be closely correlated with the prevention of recurrence.

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  • Loss of Runt-Related Transcription Factor 3 Causes Development and Progression of Hepatocellular Carcinoma 査読

    Hidenori Shiraha, Shin-ichi Nishina, Kazuhide Yamamoto

    JOURNAL OF CELLULAR BIOCHEMISTRY112 ( 3 ) 745 - 749   2011年3月

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

    Runt-related transcription factor 3 (RUNX3) is reported as a tumor suppressor gene for gastric cancer, and may be important in the development of hepatocellular carcinoma (HCC). RUNX3 expression is frequently lost or decreased by hemizygous deletion or hypermethylation of its promoter lesion in HCC. The significance of decreased expression of RUNX3 in HCC has not been fully elucidated, but is likely related to dysfunction of cell cycle regulation, decrement of apoptosis, enhancement of angiogenesis, and development of epithelial mesenchymal transition. RUNX3 is a promising candidate as a tumor suppressor gene for HCC. J. Cell. Biochem. 112: 745-749,2011. (C) 2010 Wiley-Liss, Inc.

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  • Hepatocellular carcinoma occurring in hepatobiliary fibropolycystic disease 査読

    Hideaki Kinugasa, Kazuhiro Nouso, Yoshiyuki Kobayashi, Tetuya Yasunaka, Hideki Onishi, Shin-ichiro Nakamura, Hidenori Shiraha, Hiroki Takayama, Junichi Toshimori, Kenji Kuwaki, Hiroaki Hagihara, Yasuhiro Miyake, Fusao Ikeda, Akinobu Takaki, Haruhiko Kobashi, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH41 ( 3 ) 277 - 281   2011年3月

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

    Congenital hepatic fibrosis (CHF) and bile duct hamartomas (von Meyenburg complexes) are hepatobiliary fibropolycystic diseases. There have been several reports of liver neoplasias arising in hepatobiliary fibropolycystic diseases. However, most of them were cholangiocarcinomas and cases involving hepatocellular carcinoma (HCC) are rare. A 51-year-old woman was found to have multiple hepatic tumors by ultrasonography and enhanced computed tomography (CT) during a regular work-up for the recurrence of lung cancer and thyroid cancer, which had been surgically removed 4 and 3 years ago, respectively. Nodules were observed at S3, S5, and S6 (2 cm in diameter). All of the nodules were hyperattenuated at the early arterial phase, and the main tumor at S5 showed hypoattenuation at the delayed phase on dynamic CT and magnetic resonance imaging (MRI). HCC was suspected from these findings. She also suffered from multiple small cystic lesions in the liver. The surgically removed liver showed HCC arising in CHF, which is a rare histological finding.

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  • Prognostic Model for Hepatocellular Carcinoma with Time-Dependent Factors 査読

    Kenji Kuwaki, Kazuhiro Nouso, Yoshiyuki Kobayashi, Shinichiro Nakamura, Yoichi M. Ito, Shouta Iwadou, Hiroaki Hagihara, Tetsuya Yasunaka, Junichi Toshimori, Hirokazu Miyatake, Kenji Miyoshi, Hideki Onishi, Yasuhiro Miyake, Bon Shoji, Akinobu Takaki, Hidenori Shiraha, Yoshiaki Iwasaki, Haruhiko Kobashi, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA65 ( 1 ) 11 - 19   2011年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    The purpose of this study was to build a prognostic model of hepatocellular carcinoma (HCC) using time-dependent covariates to re-evaluate the prognosis at any stage of the disease. The subjects were consecutive HCC patients who were treated at our institute between 1995 and 2007. We constructed time-fixed and time-dependent prognostic models with a training group (n = 336) and compared the prognostic abilities between conventional Cancer of the Liver Italian Program (CLIP) scores, Japan Integrated Staging (JIS) scores, an Okuda classification, and our prognostic models in the testing group (n = 227) with the c-index. The time-dependent prognostic model consisted of main tumor size, tumor number, portal vein invasion, distant metastasis, alpha-fetoprotein, des-gamma-carboxy prothrombin (DCP), bilirubin, and albumin and the weighted scores were set for each factor depending on the hazard ratio for the prognosis. The prognostic index was determined by summing the scores. The c-index values for the CLIP scores, JIS scores, Okuda classification, and our time dependent model were 0.741, 0.727, 0.609, and 0.870, respectively. These results indicate that our time-dependent model can estimate the prognosis of HCC more precisely than traditional time-fixed models and can be used to re-predict the prognosis of HCC.

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  • Serum levels of platelet-derived growth factor-BB and vascular endothelial growth factor as prognostic factors for patients with fulminant hepatic failure 査読

    Hiroki Takayama, Yasuhiro Miyake, Kazuhiro Nouso, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Haruhiko Kobashi, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY26 ( 1 ) 116 - 121   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Background and Aims:
    In animal models for acute liver injury, the administration of some angiogenic factors such as vascular endothelial growth factor (VEGF) and granulocyte-colony stimulating factor (G-CSF) are shown to reduce liver injury and improve liver proliferative capacity. The aim of the present study was to assess the role of angiogenic factors in fulminant hepatic failure (FHF).
    Methods:
    Serum levels of nine angiogenic factors (angiopoietin-2, follistatin, G-CSF, hepatocyte growth factor [HGF], interleukin-8, leptin, platelet-derived growth factor [PDGF]-BB, platelet endothelial cell adhesion molecule-1 and VEGF) were measured using the Bio-Plex Protein Array System in 30 patients, 17 of whom were diagnosed with FHF, 13 with acute hepatitis (AH), and 20 controls.
    Results:
    Serum levels of PDGF-BB and VEGF were lower in FHF patients than AH patients and controls (PDGF-BB; 2050 +/- 1572 pg/mL vs 4521 +/- 2419 pg/mL vs 8506 +/- 5500 pg/mL, VEGF; 39 +/- 38 pg/mL vs 144 +/- 122 pg/mL vs 205 +/- 121 pg/mL). By using univariate logistic regression models, serum levels of PDGF-BB and VEGF were associated with poor outcomes. Serum PDGF-BB levels were strongly correlated with serum VEGF levels (r = 0.70). Furthermore, serum PDGF-BB levels were significantly correlated with platelet counts (r = 0.79), PT activity (r = 0.37) and D.Bil/T.Bil ratio (r = 0.50), while serum VEGF levels were significantly correlated with platelet counts (r = 0.68) and PT activity (r = 0.38).
    Conclusions:
    We consider that serum levels of PDGF-BB and VEGF are worth investigating as biomarkers for predicting outcomes of FHF patients.

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  • Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis 査読

    Yutaka Nakanishi, Hidenori Shiraha, Shin-ichi Nishina, Shigetomi Tanaka, Minoru Matsubara, Shigeru Horiguchi, Masaya Iwamuro, Nobuyuki Takaoka, Masayuki Uemura, Kenji Kuwaki, Hiroaki Hagihara, Junichi Toshimori, Hideki Ohnishi, Akinobu Takaki, Shinichiro Nakamura, Yoshiyuki Kobayashi, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto

    BMC CANCER11   3   2011年1月

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

    Background: Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC).
    Methods: RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis.
    Results: RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 +/- 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 +/- 4% and 4 +/- 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation.
    Conclusion: RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.

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  • Laparoscopic findings of reddish markings predict hepatocellular carcinoma in patients with hepatitis B virus-related liver disease 査読

    Bon Shoji, Fusao Ikeda, Shin-ichi Fujioka, Haruhiko Kobashi, Tetsuya Yasunaka, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Kazuhiro Nouso, Yoshiaki Iwasaki, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY45 ( 11 ) 1172 - 1182   2010年11月

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

    For patients with chronic hepatitis due to hepatitis B virus (HBV), factors predicting hepatocellular carcinoma (HCC) other than high levels of HBV-DNA and alanine aminotransferase (ALT) are needed to prevent HCC development, as many patients with chronic HBV infection fulfill these conditions. The purpose of this study was to clarify factors predictive of HCC development for those patients.
    The study was a systematic cohort analysis of 303 consecutive patients with hepatitis B e-antigen, receiving laparoscopic examination for assessment of liver disease. Laparoscopic, histological, and clinical characteristics were investigated as related to HCC development.
    HCC occurred in 27 patients during a mean follow-up of 8.0 +/- A 5.0 years, at the age of 37-72 years. Significant associations with HCC development were shown for liver cirrhosis, histological activity grade, reddish markings, and older age. Multivariate analysis revealed that HCC development was strongly associated with older age and male gender (P = 0.002 and P = 0.043, respectively). HCC occurred more frequently in patients of age a parts per thousand yen30 years even with early stage than in patients of age < 30 years (P = 0.031). Severe reddish markings, a laparoscopic finding of widespread parenchymal destruction, were highly associated with HCC development in patients of age a parts per thousand yen30 years at diagnosis (odds ratio = 1.67, P = 0.034), while histological activity grade and ALT level were not (P = 0.075 and P = 0.69, respectively).
    HCC development is associated with older age, male gender, and liver cirrhosis. Reddish markings, rather than histological activity or ALT level, can be useful to predict HCC for HBV patients of age a parts per thousand yen30 years.

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  • Hepatitis C virus NS4 protein impairs the Th1 polarization of immature dendritic cells 査読

    A. Takaki, M. Tatsukawa, Y. Iwasaki, K. Koike, Y. Noguchi, H. Shiraha, K. Sakaguchi, E. Nakayama, K. Yamamoto

    JOURNAL OF VIRAL HEPATITIS17 ( 8 ) 555 - 562   2010年8月

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

    Dendritic cells (DCs) in chronic hepatitis C patients display impaired function, although the details remain unclear. To investigate the hepatitis C virus (HCV) protein that has the most impact on DC function, we compared five recombinant proteins and seven HCV protein genes in modulating DC phenotype and function. Immature DCs (iDCs) were established from healthy donor peripheral blood monocytes with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4. Lipopolysaccharide was used to establish mature DCs (mDCs). Cells were then pulsed with HCV recombinant proteins or transfected with HCV plasmids and subsequently assayed for cell surface marker expression by flow cytometry. For cytokine and proliferative T-cell response analysis, DCs were cultured with autologous CD4 T cells and tuberculin purified protein derivative (PPD). Mean fluorescent intensity of CD86 was reduced in HCV protein-pulsed iDCs. Proliferative T-cell responses and Th1 cytokine concentrations were reduced with HCV nonstructural proteins (NS), particularly with HCV NS4. HCV nonstructural proteins, particularly NS4, change the iDC phenotype and reduce antigen-specific T-cell stimulatory function with Th1 cytokine reductions.

    DOI: 10.1111/j.1365-2893.2009.01213.x

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  • Time-dependent analysis of predisposing factors for the recurrence of hepatocellular carcinoma 査読

    Shouta Iwadou, Kazuhiro Nouso, Kenji Kuwaki, Yoshiyuki Kobayashi, Shinichiro Nakamura, Hironori Tanaka, Kenji Miyoshi, Hideki Ohnishi, Yasuhiro Miyake, Hidenori Shiraha, Yoshiaki Iwasaki, Yasushi Shiratori, Kazuhide Yamamoto

    LIVER INTERNATIONAL30 ( 7 ) 1027 - 1032   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Background/aim: There are many reports dealing with the risk factors for hepatocellular carcinoma (HCC) recurrence. However, in most of these reported studies, factors were analysed only at the initial treatment stage, and the predisposing factors for the recurrence during follow-up have not been well studied. The aim of this study is to evaluate the predisposing factors after treatments. Methods: Two hundred and seventy-one consecutive HCC patients curatively treated between January 1994 and March 2004 were followed up and analysed. The recurrence rate was estimated by the Kaplan-Meier method and the predisposing factors were evaluated by time-fixed Cox regression analysis and by time-dependent covariate analysis using multiple parameters. Results: The mean follow-up period was 4.86 years and recurrence was observed in 169 patients (62.4%). The recurrence rates were 27.9, 65.1 and 84.3% at 1, 3 and 5 years respectively. Among the variables determined before treatment, predisposing factors for recurrence were low serum albumin [<= 3.5 g/dl, hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.07-2.01] and multiple tumour number (HR = 2.04, 95% CI = 1.46-2.84) by time-fixed multivariate analysis. In the time-dependent analysis, six variables with 12 013 plots were examined. The multivariate analysis revealed that high des-g-carboxy prothrombin (DCP >= 40mAU/ml, HR = 2.33, 95% CI = 1.61-3.39), high a-fetoprotein (AFP >= 100 ng/ml, HR = 2.01, 95% CI = 1.3-3.35) and high alanine aminotransferase (ALT >= 40 IU/L, HR = 1.52, 95% CI = 1.1-2.1) were significant predisposing factors for recurrence. Conclusion: Predisposing factors for the recurrence of HCC after treatment are different from those before treatments and special cautions are required when AFP, DCP or ALT is high during follow-up.

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  • Evolution of prognostic factors in hepatocellular carcinoma in Japan. 査読

    Nouso K, Kobayashi Y, Nakamura S, Kobayashi S, Toshimori J, Kuwaki K, Hagihara H, Onishi H, Miyake Y, Ikeda F, Shiraha H, Takaki A, Iwasaki Y, Kobashi H, Yamamoto K

    Alimentary pharmacology & therapeutics31 ( 3 ) 407 - 414   2010年2月

  • Application of Radiofrequency Ablation for the Treatment of Metastatic Liver Cancers 査読

    Kazuhiro Nouso, Yoshiyuki Kobayashi, Shinichiro Nakamura, Shuji Uematsu, Kunihiro Shiraga, Shouta Iwadou, Yasuyuki Araki, Hideaki Taniguchi, Hironori Tanaka, Nobuyuki Toshikuni, Toshihiko Kaneyoshi, Hiroshi Ikeda, Shinichi Fujioka, Toshiya Osawa, Yoshiaki Iwasaki, Hidenori Shiraha, Kazuhide Yamamoto

    HEPATO-GASTROENTEROLOGY57 ( 97 ) 117 - 120   2010年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBLISHING S A  

    Background/Aims: The aim of this study is to elucidate the effectiveness of radiofrequency ablation (RFA) for the treatment of metastatic liver cancers.
    Methodology: From 74 patients with metastatic liver cancers treated by RFA, 40 patients including 23 colon cancer who had received curative resection of the primary tumor were analyzed.
    Results: Recurrence of the tumor was observed in 29 (72.5%) patients. The most prevalent site of recurrence was the liver in both colon cancer (10/15, 66.7%) and non-colon cancer patients (12/14, 85.7%). Among the recurrence in the liver, the rate of intrahepatic distant recurrence (recurrence outside of the RFA-treated segment) was high in both colon cancer (55.6%) and non-colon cancer patients (69.0%). Local recurrence (recurrence at the RFA-treated segment) rate was low (32.6% and 32.9%, respectively) and none of single tumor less than 2cm in diameter showed local recurrence. The intrahepatic recurrence was single in 67.6% of the patients and 59.1% of the patients were re-treated by RFA.
    Conclusions: RFA is a less-invasive method for the treatment of metastatic liver tumors and can be performed repetitively. Although the rate of intra-hepatic distant recurrence and extra-hepatic recurrence was high, good local control can be achieved by RFA.

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  • Significance of Des-gamma-carboxy Prothrombin Production in Hepatocellular Carcinoma 査読

    Tatsuya Fujikawa, Hidenori Shiraha, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA63 ( 6 ) 299 - 304   2009年12月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Serum des-gamma-carboxy prothrombin (DCP) is commonly used to detect hepatocellular carcinoma (HCC). This review focuses on the clinical features of DCP-positive HCC and the molecular function of DCP in HCC. DCP-positive HCC demonstrates more aggressive clinicopathological features than DCP-negative HCC. Analysis of the biological effects of DCP revealed that DCP acts as a growth factor in both an autocrine and paracrine manner. DCP stimulates HCC cell proliferation through the Met-Janus kinase 1-signal transducer and activator of transcription 3 signaling pathway, whereas for vascular endothelial cells, it stimulates cell proliferation and migration through the kinase insert domain receptor-phospholipase C-gamma-mitogen-activated protein kinase signaling pathway.

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  • Twist expression promotes migration and invasion in hepatocellular carcinoma 査読

    Noriyuki Matsuo, Hidenori Shiraha, Tatsuya Fujikawa, Nobuyuki Takaoka, Naoki Ueda, Shigetomi Tanaka, Shinichi Nishina, Yutaka Nakanishi, Masayuki Uemura, Akinobu Takaki, Shinichiro Nakamura, Yoshiyuki Kobayashi, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto

    BMC CANCER9   240   2009年7月

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

    Background: Twist, a transcription factor of the basic helix-loop-helix class, is reported to regulate cancer metastasis. It is known to induce epithelial-mesenchymal transition (EMT). In this study, we evaluated the expression of twist and its effect on cell migration in hepatocellular carcinoma (HCC).
    Methods: We examined twist expression using immunohistochemistry in 20 tissue samples of hepatocellular carcinoma, and assessed twist expression in HCC cell lines by RT-PCR and Western blot analysis. Ectopic twist expression was created by introducing a twist construct in the twist-negative HCC cell lines. Endogenous twist expression was blocked by twist siRNA in the twist-positive HCC cell lines. We studied EMT related markers, E-cadherin, Vimentin, and N-cadherin by Western blot analysis. Cell proliferation was measured by MTT assay, and cell migration was measured by in vitro wound healing assay. We used immunofluorescent vinculin staining to visualize focal adhesion.
    Results: We detected strong and intermediate twist expression in 7 of 20 tumor samples, and no significant twist expression was found in the tumor-free resection margins. In addition, we detected twist expression in HLE, HLF, and SK-Hep1 cells, but not in PLC/RPF/5, HepG2, and Huh7 cells. Ectopic twist-expressing cells demonstrated enhanced cell motility, but twist expression did not affect cell proliferation. Twist expression induced epithelial-mesenchymal transition together with related morphologic changes. Focal adhesion contact was reduced significantly in ectopic twist-expressing cells. Twist-siRNA-treated HLE, HLF, and SK-Hep1 cells demonstrated a reduction in cell migration by 50, 40 and 18%, respectively.
    Conclusion: Twist induces migratory effect on hepatocellular carcinoma by causing epithelial-mesenchymal transition.

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  • A case of primary intracranial hemangiopericytoma with hepatic metastases: Successful treatment with radiofrequency ablation and transcatheter arterial chemoembolization 査読

    Masaya Iwamuro, Shinichiro Nakamura, Hidenori Shiraha, Yoshiyuki Kobayashi, Hirotoshi Fukatsu, Kazuhide Yamamoto

    Clinical Journal of Gastroenterology2 ( 1 ) 30 - 35   2009年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Intracranial hemangiopericytoma is an uncommon soft tissue sarcoma. We report a case of a 54-year-old Japanese female with hepatic metastasis from primary intracranial hemangiopericytoma. At age 44 years the patient underwent primary resection of the intracranial tumor, followed by no adjuvant therapy. At age 53 years she underwent resection of bone metastases in her left upper arm and tenth right rib. The following year, three hepatic tumors with high vascularity were detected by ultrasonography, computed tomography scans, and magnetic resonance imaging. An ultrasound-guided liver biopsy specimen confirmed the diagnosis of hepatic metastases from the primary intracranial hemangiopericytoma. A combination therapy of transcatheter arterial chemoembolization and radiofrequency ablation was performed against the hepatic metastasis. After 5 years, there has been no local recurrence in the liver. © 2008 Springer.

    DOI: 10.1007/s12328-008-0033-0

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  • Exon 2 deletion splice variant of gamma-glutamyl carboxylase causes des-gamma-carboxy prothrombin production in hepatocellular carcinoma cell lines 査読

    Naoki Ueda, Hidenori Shiraha, Tatsuya Fujikawa, Nobuyuki Takaoka, Yutaka Nakanishi, Mayumi Suzuki, Noriyuki Matsuo, Shiyetomi Tanaka, Shin-ichi Nishina, Masayuki Uemura, Akinobu Takaki, Yasushi Shiratori, Kazuhide Yamamoto

    MOLECULAR ONCOLOGY2 ( 3 ) 241 - 249   2008年10月

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

    Using GGCX gene-specific real-time PCR, exon 2 deletion splice variant of vitamin K-dependent gamma-glutamyl carboxylase (GGCX) mRNA was identified in HCC cell lines. Expressions of wild type and exon 2 deletion variant of GGCX were analyzed with relevance to DCP production in HCC cell lines. Hep3B, HepG2, HuH1, HuH7, and PLC/PRF/5 produced DCP, while SK-Hep-1, HLE, HLF, and JHH1 produced no detectable level of DCP. DCP-producing cells expressed exon 2 deletion variant of GGCX mRNA and protein, while DCP-negative cells expressed no detectable level of exon 2 deletion variant of GGCX. These results suggest that exon 2 deletion splice variant of GGCX causes dysfunction of GGCX enzyme activity resulting in DCP production in HCC cell lines. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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  • Hepatitis B virus DNA in liver tissue and risk for hepatocarcinogenesis in patients with hepatitis C virus-related chronic liver disease 査読

    Mikako Obika, Toshiyuki Shinji, Shin-ichi Fujioka, Ryo Terada, Hiromasa Ryuko, Aye Aye Lwin, Hidenori Shiraha, Norio Koide

    INTERVIROLOGY51 ( 1 ) 59 - 68   2008年

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

    Aims: To prospectively study whether occult hepatitis B virus (HBV) infection can promote the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related chronic liver disease. In addition, to evaluate the difference among HBV DNA-negative patients and patients with high and low HBV copy numbers. Methods: A total of 167 patients with HCV-related chronic liver disease without HBV surface antigen ( HBsAg) were studied. HBV DNA in liver tissue was determined using polymerase chain reaction (PCR). Results: HBV DNA was detected in 9 of 167 patients (5.4%) by single PCR and in 25 patients (15.0%) by nested PCR. HCC developed in 12 of 167 patients (7.2%). Ten of 142 HBV DNA-negative patients (7.0%) and 2 of 9 patients with a high HBV copy number (22.2%) developed HCC, whereas none of 16 patients with a low HBV copy number developed HCC. The incidence rate of HCC in patients with a high HBV copy number was significantly higher than in HBV DNA-negative patients and patients with low HBV copy number. Conclusion: A high amount of HBV DNA in liver tissue of HBsAg-negative patients with HCV-related liver disease might be associated with HCC development. Copyright (c) 2008 S. Karger AG, Basel.

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  • Decreased expression of hMLH1 correlates with reduced 5-fluorouracil-mediated apoptosis in colon cancer cells 査読

    Hideyuki Fujita, Jun Kato, Joichiro Horii, Keita Harada, Sakiko Hiraoka, Hidenori Shiraha, Kohsaku Sakaguchi, Yasushi Shiratori

    ONCOLOGY REPORTS18 ( 5 ) 1129 - 1137   2007年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    Patients with sporadic microsatellite instable colorectal cancers, in most of which the function of the hMLH1 mismatch repair gene is impaired, do not gain a survival benefit from 5-fluorouracil (5-FU)-based chemotherapy. However, the effect of hMLH1 on the cytotoxicity induced by 5-FU has not yet been sufficiently confirmed. In this study, we assessed the effect of hMLH1 on cytotoxicity and apoptosis induced by 5-FU using newly developed cell lines. We constructed two cell lines: SW480 (originally hMLH1-proficient), in which the expression of hMLH1 was reduced using a small interfering RNA (siRNA) technique, and HCT116 (originally hMLH1-deficient), in which the expression of hMLH1 can be regulated by doxycycline. Using these, cell lines, a clonogenic survival assay, 4',6-diamidino-2-phenylindole (DAPI) staining and an Annexin-V assay were performed. Moreover, the incorporation of 5-FU into DNA was determined using tritium-labeled 5-FU. In both of our two cell lines, hMLH1-deficient cells exhibited approximately 2.4-fold clonal surviving fraction compared to hMLH1-proficient cells for 10 days after the administration of 5-FU. Additionally, hMLH1-deficient cells treated with 5-FU exhibited 34-45% less apoptosis than hMLH1-proficient cells according to the results of DAPI staining and Annexin-V assay. Furthermore, hMLH1-deficient cells treated with 5-FU exhibited an approximately 2-fold greater incorporation of 5-FU into DNA than control cells, suggesting that the recognition of 5-FU-incorporated DNA is impaired in hMLH1-deficient cells, resulting in reduced apoptosis. Our conclusions were that decreased expression of hMLH1 in colon cancer cells reduced the apoptosis induced by 5-M, suggesting that hMLH1 is a key determinant of 5-FU chemosensitivity.

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  • Cimetidine inhibits epidermal growth factor-induced cell signaling 査読

    Tatsuya Fujikawa, Hidenori Shiraha, Yutaka Nakanishi, Nobuyuki Takaoka, Naoki Ueda, Mayumi Suzuki, Yasushi Shiratori

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY22 ( 3 ) 436 - 443   2007年3月

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

    Background: Cimetidine, a histamine-2 (H-2) receptor antagonist, has been demonstrated to have anticancer effects on colorectal cancer, melanoma and renal cell carcinoma. In the current study, we clarified that cimetidine inhibits both epidermal growth factor (EGF)-induced cell proliferation and migration in hepatocellular carcinoma (HCC) cell lines.
    Method: HCC cell lines (Hep3B, HLF, SK-Hep-1, JHH-2, PLC/PRF/5 and HLE) were used and cell proliferation was assessed by [H-3]-thymidine incorporation assay. Cell migration was measured by in vitro cell migration assay. Biological effects of cimetidine were assessed with human EGF receptor (EGFR)-expressing mouse fibroblast cells (NR6-WT). The autophosphorylation of EGFR and the activation of other downstream effectors were analyzed by immunoprecipitation and immunoblotting. The concentration of intracellular cyclic AMP (cAMP) was measured by competitive enzyme immunoassay.
    Results: Cimetidine inhibited both EGF-induced cell proliferation and migration in Hep3B, HLF, SK-Hep-1 and JHH-2, while cimetidine did not affect EGF-induced cell proliferation and migration in PLC/PRF/5 and HLE. Cimetidine was revealed to disrupt the EGF-induced autophosphorylation of EGFR and its downstream effectors, mitogen activated protein kinases and phospholipase C-gamma. To define the molecular basis of this negative regulation, we identified that cimetidine significantly decreased intracellular cAMP levels and that decrement of cAMP inhibited autophosphorylation of EGFR. The cell permeable cAMP analog, CPT-cAMPS reversed the cimetidine-induced inhibition of EGF-induced cell proliferation and cell migration by restoring autophosphorylation of EGFR.
    Conclusion: Cimetidine inhibited EGF-induced cell proliferation and migration in HCC cell lines by decreasing the concentration of intracellular cAMP levels. Cimetidine may be a candidate chemopreventive agent for HCC.

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  • Des-gamma-carboxyl prothrombin-promoted vascular endothelial cell proliferation and migrations 査読

    Tatsuya Fujikawa, Hidenori Shiraha, Naoki Ueda, Nobuyuki Takaoka, Yutaka Nakanishi, Noriyuki Matsuo, Shigetomi Tanaka, Shin-ichi Nishina, Mayumi Suzuki, Akinobu Takaki, Kohsaku Sakaguchi, Yasushi Shiratori

    JOURNAL OF BIOLOGICAL CHEMISTRY282 ( 12 ) 8741 - 8748   2007年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Des-gamma-carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma. Previously, we have demonstrated that DCP stimulates cell proliferation in hepatocellular carcinoma cell lines through Met-Janus kinase 1 signal transducer and activator of transcription 3 signaling pathway. In the present study, we demonstrated that DCP induces both cell proliferation and migration in human umbilical vein endothelial cells. DCP was found to bind with the kinase insert domain receptor (KDR), alternatively referred to as vascular endothelial growth factor receptor-2. Furthermore, DCP induced autophosphorylation of KDR and its downstream effector phospholipase C-gamma and mitogen-activated protein kinase (MAPK). To support these results, we showed that DCP-induced cell proliferation and cell migration were inhibited by KDR short interfering RNA, KDR kinase inhibitor, or MAPK inhibitor. In conclusion, these results indicate that DCP is a novel type of vascular endothelial growth factor that possesses potent mitogenic and migrative activities.

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  • Peritoneal dissemination of hepatocellular carcinoma treated with a combination therapy of interferon-alpha-2b and oral tegafur/uracil 査読

    Yasuhiro Miyake, Yoshiaki Iwasaki, Hidenori Shiraha, Kohsaku Sakaguchi, Yasushi Shiratori

    INTERNAL MEDICINE46 ( 9 ) 565 - 569   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    We encountered a case of peritoneal dissemination of hepatocellular carcinoma, successfully treated with a combination therapy of interferon-alpha-2b and oral tegafur/uracil. A 67-year-old Japanese man who underwent a hepatectomy developed peritoneal dissemination. A combination therapy of subcutaneous interferon-alpha-2b and intravenous 5-fluorouracil was started. Four weeks later, he felt severe general fatigue and nausea, and intravenous 5-fluorouracil was replaced with oral tegafur/uracil. At 3 months after the initiation of chemotherapy, enhanced computed tomography showed markedly reduced peritoneal dissemination. A combination therapy of interferon-alpha-2b and oral tegafur/uracil is facile and may be effective for extrahepatic metastasis of hepatocellular carcinoma.

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  • Combination of 5-FU and IFN alpha enhances IFN signaling pathway and caspase-8 activity, resulting in marked apoptosis in hepatoma cell lines 査読

    Kazuko Koike, Akinobu Takaki, Masashi Tatsukawa, Mayumi Suzuki, Hidenori Shiraha, Yoshiaki Iwasaki, Kohsaku Sakaguchi, Yasushi Shiratori

    INTERNATIONAL JOURNAL OF ONCOLOGY29 ( 5 ) 1253 - 1261   2006年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    Interferon (IFN) combined with 5-Fluorouracil (5-FU) treatment has recently been reported to show beneficial effects in patients with advanced hepatocellular carcinoma. IFNa is usually provided for this combination therapy. In this study, we investigated the molecular mechanisms of apoptosis induction in hepatoma cell lines with IFNa and 5-FU combination therapy from the view point of 5-FU's additive effect on interferon-related signaling pathways. Five hepatoma cell lines (Hep3B, Huh7, HLE, PLC/PRF/5, and HepG2) were tested for apoptosis inducibility by IFN alpha in the absence or presence of 5-FU. Hep3B was the most apoptosis sensitive to IFN plus 5-FU treatment. The JAK/STAT pathway transcriptional factor ISRE was activated more synergistically when 5-FU was added to IFN alpha treatments. Caspase-3, -9, and especially caspase-8 activity was higher with IFN a plus 5-FU than IFN or 5-FU alone. Inhibition of caspase-8, -9, c-Jun N-terminal kinase (INK), phosphatidylinositide 3-kinase (PI3K), and p38 mitogen-activated protein kinase (p38 MAPK) revealed that caspase-8 inhibition was the most effective at decreasing the apoptotic effects of IFN and/or 5-FU. In JAK1 and ISGF3y-silenced Hep3B cells, the apoptosis induction and caspase-8 activation levels by IFN, even in combination with 5-FU, were abrogated. In conclusion, caspase-8 is the most important factor that controls IFN and 5-FU-induced apoptosis in hepatoma cell lines.

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  • Laterally spreading type of colorectal adenoma exhibits a unique methylation phenotype and K-ras mutations 査読

    Sakiko Hiraoka, Jun Kato, Masashi Tatsukawa, Keita Harada, Hideyuki Fujita, Tamiya Morikawa, Hidenori Shiraha, Yasushi Shiratori

    GASTROENTEROLOGY131 ( 2 ) 379 - 389   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Background & Aims: Laterally spreading tumors (LST), characterized by superficial extension along the colonic lumen, have recently been detected by colonoscopy. However, genetic and epigenetic characteristics of these tumors were scarcely reported. Methods: A total of 205 sporadic colorectal adenoma tissues (157 protruded-type, 23 granular-type LST (G-LST), 12 flat-type LST (FLST), and 13 flat-type smaller than 1 cm) were collected. CpG island methylator phenotype (CIMP) was determined by examination of methylation status at p16, methylated in tumor (MINT) 1, 2, 12, and 31 loci. K-ras codon 12 and 13 point mutations were also examined. The relationship between macroscopic appearance and CIMP status or K-ras mutations was analyzed. Results: Among adenomas larger than 1 cm, CpG island methylation involving 2 or more loci (CIMP-high) was more likely to be observed in G-LST (14/23, 61%) than in protruded-type adenomas (18/73, 25%) (P=.002). The prevalence of K-ras mutations in G-LST (18/23, 78%) was significantly higher than that in protruded-type adenomas (18/73, 25%) (P <.0001). Moreover, the prevalence of CIMP-high and K-ras mutations in G-LST located in the proximal colon was much higher (11/13, 85%; and 12/13, 92%, respectively). In contrast, F-LST exhibited low prevalence of CIMP-high (1/12, 8%) and K-ras mutations (2/12, 16%). Conclusions: High prevalence of CIMP-high and K-ras mutations in G-LST, especially in the proximal colon, could strongly suggest that G-LST appearance is associated with a unique carcinogenic pathway.

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  • Early detection and quantification of lamivudine-resistant hepatitis B virus mutants by fluorescent biprobe hybridization assay in lamivudine-treated patients 査読

    Fumi Umeoka, Yoshiaki Iwasaki, Masayuki Matsumura, Akinobu Takaki, Haruhiko Kobashi, Masashi Tatsukawa, Hidenori Shiraha, Shin-ichi Fujioka, Kohsaku Sakaguchi, Yasushi Shiratori

    JOURNAL OF GASTROENTEROLOGY41 ( 7 ) 693 - 701   2006年6月

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

    Background. Long-term lamivudine treatment induces the emergence of lamivudine-resistant hepatitis B virus (HBV). The objective of this study was to develop a fluorescent biprobe hybridization (FBH) assay for the detection and quantification of HBV mutants in the clinical course of lamivudine-treated patients and to evaluate its clinical usefulness. Methods. We developed an FBH assay to detect mutations in the HBV DNA polymerase gene. The assay's detection sensitivity was determined using a dilution series of wild-type/mutant plasmid DNA. Blood samples obtained from 27 lamivudine-treated patients were analyzed. Results. Mutant DNA levels as low as 10% of total HBV DNA were detected (sensitivity = 100%, specificity = 80%). HBV mutants were detected in five of the 27 patients during an average follow-up of 20 months after lamivudine administration. In one of the five patients, the YIDD mutant was detected at the initiation of lamivudine treatment, while the remaining four patients were identified as having YIDD mutants within 3 months after beginning lamivudine administration. Of the five patients with an HBV mutant, four developed breakthrough hepatitis more than 10 months after the detection of HBV mutants, following the reappearance or a re-increase of HBV DNA, characterized by a predominance of the mutant. The YIDD mutant was detected in one patient, even when the titer of the serum HBV DNA was below the detection limit of commercially available quantitative polymerase chain reaction. Conclusions. The FBH assay is an efficient method for detecting and quantifying HBV mutants, as early as 3 months after lamivudine administration.

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  • Des-gamma-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma 査読

    M Suzuki, H Shiraha, T Fujikawa, N Takaoka, N Ueda, Y Nakanishi, K Koike, A Takaki, Y Shiratori

    JOURNAL OF BIOLOGICAL CHEMISTRY280 ( 8 ) 6409 - 6415   2005年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Des-gamma-carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma (HCC). In the present study, we demonstrate that DCP has a mitogenic effect on HCC cell lines. Purified DCP stimulated DNA synthesis of Hep3B and SK-Hep-1 cells in a dose-dependent manner. DCP was found to bind with cell surface receptor Met causing Met autophosphorylation and also to activate STAT3 signaling pathway through Janus kinase 1. Luciferase gene reporter analysis showed that DCP induced STAT3-related transcription. Small interfering RNAs against both STAT3 and Met abrogated DCP-induced cell proliferation. DCP did not affect the mitogen-activated protein kinase pathway, Myc signaling pathway, or phosphoinositide 3-kinase/Akt pathway. Based on these results, we believe that DCP acts as an autologous mitogen for HCC cell lines. The Met-Janus kinase 1-STAT3 signaling pathway may be a major signaling pathway for DCP-induced cell proliferation.

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  • Functional promoter upstream p53 regulatory sequence of IGFBP3 that is silenced by tumor specific methylation 査読

    T Hanafusa, T Shinji, H Shiraha, K Nouso, Y Iwasaki, E Yumoto, T Ono, N Koide

    BMC CANCER5   9   2005年1月

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

    Background: Insulin-like growth factor binding protein (IGFBP)-3 functions as a carrier of insulin-like growth factors (IGFs) in circulation and a mediator of the growth suppression signal in cells. There are two reported p53 regulatory regions in the IGFBP3 gene; one upstream of the promoter and one intronic. We previously reported a hot spot of promoter hypermethylation of IGFBP-3 in human hepatocellular carcinomas and derivative cell lines. As the hot spot locates at the putative upstream p53 consensus sequences, these p53 consensus sequences are really functional is a question to be answered.
    Methods: In this study, we examined the p53 consensus sequences upstream of the IGFBP-3 promoter for the p53 induced expression of IGFBP-3. Deletion, mutagenesis, and methylation constructs of IGFBP-3 promoter were assessed in the human hepatoblastoma cell line HepG2 for promoter activity.
    Results: Deletions and mutations of these sequences completely abolished the expression of IGFBP-3 in the presence of p53 overexpression. In vitro methylation of these p53 consensus sequences also suppressed IGFBP-3 expression. In contrast, the expression of IGFBP-3 was not affected in the absence of p53 overexpression. Further, we observed by electrophoresis mobility shift assay that p53 binding to the promoter region was diminished when methylated.
    Conclusion: From these observations, we conclude that four out of eleven p53 consensus sequences upstream of the IGFBP-3 promoter are essential for the p53 induced expression of IGFBP-3, and hypermethylation of these sequences selectively suppresses p53 induced IGFBP-3 expression in HepG2 cells.

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  • [Evaluating the efficacy of interferon therapy on hepatitis C patients]. 査読

    Shiraha H, Iwasaki Y, Shiratori Y

    Nihon rinsho. Japanese journal of clinical medicine62 Suppl 7 ( Pt 1 ) 489 - 492   2004年7月

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  • Analysis of HCV genotypes from blood donors shows three new HCV type 6 subgroups exist in Myanmar 査読

    T Shinji, YY Kyaw, K Gokan, Y Tanaka, K Ochi, N Kusano, T Mizushima, S Fujioka, H Shiraha, AA Lwin, Y Shiratori, M Mizokami, M Khin, M Miyahara, S Okada, N Koide

    ACTA MEDICA OKAYAMA58 ( 3 ) 135 - 142   2004年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    The prevalence of hepatitis C virus (HCV) genotypes in Myanmar in comparison with the rest of Southeast Asia is not well known. Serum samples were obtained from 201 HCV antibody-positive volunteer blood donors in and around the Myanmar city of Yangon. Of these, the antibody titers of 101 samples were checked by serial dilution using HCV antibody PA test II and Terasaki microplate as a low-cost method. To compare antibody titers by this method and RNA identification, we also checked HCV-RNA using the Amplicor 2.0 test. Most high-titer groups were positive for HCV-RNA. Of the 201 samples, 110 were successfully polymerase chain reaction (PCR) amplified. Among them, 35 (31.8%) were of genotype 1, 52 (47.3%) were of genotype 3, and 23 (20.9%) were of type 6 variants, and phylogenetic analysis of these type 6 variants revealed that 3 new type 6 subgroups exist in Myanmar. We named the subgroups M6-1, M6-2, and M6-3. M6-1 and M6-2 were relatively close to types 8 and 9, respectively. M6-3, though only found in one sample, was a brand-new subgroup. These subtypes were not seen in Vietnam, where type 6 group variants are widely spread. These findings may be useful for analyzing how and when these subgroups were formed.

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  • Epidermal growth factor activates m-calpain (calpain II), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation 査読

    A Glading, RJ Bodnar, IJ Reynolds, H Shiraha, L Satish, DA Potter, HC Blair, A Wells

    MOLECULAR AND CELLULAR BIOLOGY24 ( 6 ) 2499 - 2512   2004年3月

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

    How m-calpain is activated in cells has challenged investigators because in vitro activation requires near-millimolar calcium. Previously, we demonstrated that m-calpain activation by growth factors requires extracellular signal-regulated kinase (ERK); this enables tail deadhesion and allows productive motility. We now show that ERK directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (EGF)-induced calpain activation in vitro and in vivo. Replacing the serine with alanine limits activation by EGF and subsequent cell deadhesion and motility. A construct with the serine converted to glutamic acid displays constitutive activity in vivo; expression of an estrogen receptor fusion construct produces a tamoxifen-sensitive enzyme. Interestingly, EGF-induced m-calpain activation occurs in the absence of increased intracellular calcium levels; EGF triggers calpain even in the presence of intracellular calcium chelators and in calcium-free media. These data provide evidence that m-calpain can be activated through the ERK cascade via direct phosphorylation and that this activation may occur in the absence of cytosolic calcium fluxes.

    DOI: 10.1128/MCB.24.6.2499-2512.2004

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  • Activation of m-calpain (calpain II) by epidermal growth factor is limited by protein kinase a phosphorylation of m-calpain 査読

    H Shiraha, A Glading, J Chou, ZC Jia, A Wells

    MOLECULAR AND CELLULAR BIOLOGY22 ( 8 ) 2716 - 2727   2002年4月

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

    We have shown previously that the ELR-negative CXC chemokines interferon-inducible protein 10, monokine induced by gamma interferon, and platelet factor 4 inhibit epidermal growth factor (EGF)-induced m-calpain activation and thereby EGF-induced fibroblast cell motility (H. Shiraha, A. Glading, K. Gupta, and A. Wells, J. Cell Biol. 146:243-253, 1999). However, how this cross attenuation could be accomplished remained unknown since the molecular basis of physiological m-calpain regulation is unknown. As the initial operative attenuation signal from the CXCR3 receptor was cyclic AAIP (cAMP), we verified that this second messenger blocked EGF-induced motility of fibroblasts (55% +/- 4.5% inhibition) by preventing rear release during active locomotion. EGF-induced calpain activation was inhibited by cAMP activation of protein kinase A (PKA), as the PKA inhibitors H-89 and Rp-8Br-cAMPS abrogated cAMP inhibition of both motility and calpain activation. We hypothesized that PKA might negatively modulate m-calpain in an unexpected manner by directly phosphorylating m-calpain. A mutant human large subunit of m-calpain was genetically engineered to negate a putative PKA consensus sequence in the regulatory domain III (ST369/370AA) and was expressed in NR6WT mouse fibroblasts to represent about 30% of total m-calpain in these cells. This construct was not phosphorylated by PICA in vitro while a wild-type construct was, providing proof of the principle that m-calpain can be directly phosphorylated by PKA at this site. cAMP suppressed EGF-induced calpain activity of cells overexpressing a control wild-type human m-calpain (83% +/- 3.7% inhibition) but only marginally suppressed that of cells expressing the PKA-resistant mutant human m-calpain (25% +/- 5.5% inhibition). The EGF-induced motility of the cells expressing the PKA-resistant mutant also was not inhibited by cAMP. Structural modeling revealed that new constraints resulting from phosphorylation at serine 369 would restrict domain movement and help "freeze" m-calpain in an inactive state. These data point to a novel mechanism of negative control of calpain activation, direct phosphorylation by PKA.

    DOI: 10.1128/MCB.22.8.2716-2727.2002

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  • Kinetics of expression of connective tissue growth factor gene during liver regeneration after partial hepatectomy and D-galactosamine-induced liver injury in rats 査読

    K Ujike, T Shinji, S Hirasaki, H Shiraha, M Nakamura, T Tsuji, N Koide

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS277 ( 2 ) 448 - 454   2000年10月

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

    Connective tissue growth factor (CTGF) it regulated by TGF-beta1 during wound healing. The present study examined the expression of CTGF during regeneration after 70% partial hepatectomy (PH) or D-galactosamine (GalN)-injured liver in rats. CTGF, TGF-beta1, and type I collagen mRNAs were semiquantified by a ribonuclease protection assay. After PH, TGF-beta1 and type I collagen were increased at 2-6 h and at 12-48 h. CTGF increased at 6 h and returned to the control level thereafter. The ribonuclease protection assay of cultured hepatic stellate cells (HSC) and in situ hybridization suggest that the cells express CTGF along sinusoid might be HSCs. After GalN administration, CTGF increased at 2-96 h with a shoulder peak at 6-12 h followed by a main peak at 24 h. TGF-beta1 and type I collagen were up-regulated with kinetics similar to those of CTGF. The different kinetics between PH and GalN regenerations indicate that regulation of CTGF in the two processes is different. Higher TGF-beta1 expression after inflammatory/necrotic process in the GalN regeneration may caused the prolonged CTGF expression. (C) 2000 Academic Press.

    DOI: 10.1006/bbrc.2000.3693

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  • Aging fibroblasts present reduced epidermal growth factor (EGF) responsiveness due to preferential loss of EGF receptors 査読

    H Shiraha, K Gupta, K Drabik, A Wells

    JOURNAL OF BIOLOGICAL CHEMISTRY275 ( 25 ) 19343 - 19351   2000年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Wound healing is compromised in aging adults in part due to decreased responsiveness of fibroblasts to extracellular signals. However, the cellular mechanisms underlying this phenomenon are not known. Aged dermal fibroblasts with reduced remaining replicative capacities demonstrated decreased epidermal growth factor (EGF)-induced cell migrative and cell proliferative capacities, as reported previously. Thus, as cells approach senescence, programmed in vivo or in vitro, EGF responsiveness is preferentially lost. To define the rate-limiting signaling event, we found that the activity of two different EGF receptor (EGFR)-signaling pathways to cell migration (phospholipase-C gamma) and/or mitogenesis (extracellular signal/regulated-mitogen-activated kinases) were decreased in near senescent cells despite unchanged levels of effector molecules. Aged cells presented decreased levels of EGFR, although insulin receptor and transferrin receptor levels were relatively unchanged. EGFR, mRNA levels and production of new transcripts decreased during aging, suggesting that this preferential loss of EGFR was due to diminished production, which more than counteracts the reduced ligand-induced receptor loss. Since these data suggested that the decrement in EGF was rate-limiting, higher levels of EGFR were established in near senescent cells by electroporation of EGFR cDNA. These cells presented higher levels of EGFR and recovered their EGF-induced migration and proliferation responsiveness. Thus, the defect in EGF responsiveness of aged dermal fibroblasts is secondary to reduced EGFR message transcription. Our experimental model suggests that EGFR gene delivery might be an effective future therapy for compromised wound healing.

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  • IP-10 inhibits epidermal growth factor-induced motility by decreasing epidermal growth factor receptor-mediated calpain activity 査読

    H Shiraha, A Glading, K Gupta, A Wells

    JOURNAL OF CELL BIOLOGY146 ( 1 ) 243 - 253   1999年7月

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

    During wound healing, fibroblasts are recruited from the surrounding tissue to accomplish repair. The requisite migration and proliferation of the fibroblasts is promoted by growth factors including those that activate the epidermal growth factor receptor (EGFR), Counterstimulatory factors in wound fluid are postulated to limit this response; among these factors is the ELR-negative CXC chemokine, interferon inducible protein-10 (IP-10),We report here that IP-10 inhibited EGF- and heparin-binding EGF-like growth factor-induced Hs68 human dermal fibroblast motility in a dose-dependent manner (to 52% and 44%, respectively, at 50 ng/ml IP-10), whereas IP-10 had no effect on either basal or EGFR-mediated mitogenesis (96 +/- 15% at 50 ng/ml). These data demonstrate for the first time a counterstimulatory effect of IP-10 on a specific induced fibroblast response, EGFR-mediated motility.
    To define the molecular basis of this negative transmodulation of EGFR signaling, we found that IP-10 did not adversely impact receptor or immediate postreceptor signaling as determined by tyrosyl phosphorylation of EGFR and two major downstream effecters phospholipase C-gamma and erk mitogen-activated protein kinases, Morphological studies suggested which biophysical steps may be affected by demonstrating that IP-10 treatment resulted in an elongated cell morphology reminisce:nt of failure to detach the uropod; in support of this, IP-10 pretreatment inhibited EGF-induced cell detachment. These data suggested that calpain activity may be involved. The cell permeant agent, calpain inhibitor I, limited EGF-induced motility and de-adhesion similarly to IP-10, IP-10 also prevented EGF induced calpain activation (reduced by 71 +/- 7%).That this inhibition of EGF-induced calpain activity was secondary to IP-10 initiating a cAMP-protein kinase A-calpain cascade is supported by the following evidence: (a:) the cell permeant analogue 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) prevented EGF-induced calpain activity and motility; (b) other ELR-negative CXC chemokines, monokine induced by IFN-gamma and platelet factor 4 that also generate cAMP, inhibited EGF-induced cell migration and calpain activation; and (c) the protein kinase A inhibitor Rp-8-Br-cANIPS abrogated IP-10 inhibition of cell migration, cell detachment, and calpain activation. Our findings provide a model by which IP-10 suppresses EGF-induced cell motility by inhibiting EGF-induced detachment of the trailing edges of motile cells.

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  • Point mutations in the S and pre-S2 genes observed in two hepatitis B virus carriers positive for antibody to hepatitis B surface antigen 査読

    T Shinji, N Koide, T Hanafusa, H Hada, T Oka, N Takayama, H Shiraha, M Nakamura, K Ujike, Y Yumoto, T Tsuji

    HEPATO-GASTROENTEROLOGY45 ( 20 ) 500 - 502   1998年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBL LTD.  

    Two hepatitis B virus (HBV) carriers who had antibodies to HBV surface antigen (anti-HBs) were studied. Case 1 was a 47 year old woman positive for hepatitis B e antigen (HBeAg), and case 2 was a 61 year old man positive for antibody to HBeAg (anti-HBe) and DNA-polymerase (DNA-p). Neither case had received the HBV vaccine. The nucleotide sequences of the HBV-DNA extracted from the patients' sera were determined within the pre-S2 and S genes. Seven out of nine S gene clones from case I and six out of nine S gene clones from case 2 had an amino acid replacement from Thr or lie to Ser at codon 126 in the alpha-determinant of the S gene. Amino acid substitution of codon 145 of the S gene previously reported was not observed. Although two previous reports on HBV escape mutant carriers with both anti-HBs and HBeAg described some deletions in the pre-Sa gene, our cases did not show these deletions. Our analysis indicated that carriers with the HBV escape mutant did not always have pre-Sa gene deletions. We found two HBV escape mutant carriers who had amino acid substitutions at codon 126 in the S gene due to point mutation without any deletions in the pre-S2 gene.

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  • Reciprocal gene expression of rat fibroglycan and beta-actin during the course of regeneration after D-galactosamine liver injury 査読

    T Shinji, N Koide, H Hada, S Sasaki, T Oka, N Takayama, H Shiraha, K Ujike, M Nakamura, T Hanafusa, Y Yumoto, T Tsuji

    HEPATO-GASTROENTEROLOGY44 ( 13 ) 239 - 244   1997年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBL LTD.  

    Background/Aims: Fibroglycan (FG) is a major heparan sulfate proteoglycan. (HSPG) in. the rat Liver that is mainly distributed on. the surface of hepatocytes. HSPG may play some important roles in the regeneration of liver by interacting with various growth factors such as bFGF and HB-EGF. However, little is known about the function. of FG. We reported that after injury caused by D-galactosamine, regeneration started on the following day and peaked on day 2. To clarify the function. of FG in Liver regeneration, we investigated the gene expression of FG during regeneration after D-galactosamine injury.
    Materials and Methods: Rats were given D-galactosamine on day 0. Liver RNA was collected from day 0 to day 7. The gene expression of FG and beta-actin (as a representative cytoskeleton) was examined by Northern and/or Slot blotting.
    Results: FG gene expression was markedly decreased on. day 2, but totally recovered on day 3. In contrast, beta-actin. gene expression was markedly increased on day 2 and returned to the normal level on. day 3. Expression, of the FG and beta-actin genes was reciprocal.
    Conclusion: FG expression is transiently suppressed when cytoskeleton gene expression is enhanced at the early phase of liver regeneration.

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  • Promoter-independent loss of mRNA and protein of the Rb gene in a human hepatocellular carcinoma 査読

    H Hada, N Koide, T Morita, H Shiraha, T Shinji, M Nakamura, K Ujike, N Takayama, T Oka, T Hanafusa, Y Yumoto, K Hamazaki, T Tsuji

    HEPATO-GASTROENTEROLOGY43 ( 11 ) 1185 - 1189   1996年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBL LTD.  

    Background: Inactivation of the retinoblastoma (Rb) gene is considered to play a fundamental role in the genesis and progression of several human cancers. In retinoblastoma, the inactivation of Rb promoter by mutations or hypermethylation has been reported. Although genetic changes of Rb gene have been described in hepatocellular carcinoma (HCC) an, epigenetic change such as hypermethylation of the Rb promoter as reported in, retinoblastoma has not been described.
    Materials and Methods: We examined the hypermethylation in the promoter region of Rb gene by restriction fragment length polymorphism in 19 HCCs, as well as the expression of Rb mRNA and protein by RT-PCR and by immunoblotting, respectively.
    Results: We found no evidence of hypermethylation. in the promoter region, of the Rb gene in all HCCs analyzed. However, the expression of Rb mRNA and protein was lost in one HCC, and no mutation was detected in the Rb promoter region of this patient. The inactivation of Rb promoter by hypermethylation or by inhibition of binding of transcription factors due to point mutations did not contribute to the loss of mRNA and protein in. the patient.
    Conclusions: Hypermethylation in the Rb promoter region appeared to have little causal effect on HCC.

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  • Improvement of serum amino acid profile in hepatic failure with the bioartificial liver using multicellular hepatocyte spheroids 査読

    H Shiraha, N Koide, H Hada, K Ujike, M Nakamura, T Shinji, S Gotoh, T Tsuji

    BIOTECHNOLOGY AND BIOENGINEERING50 ( 4 ) 416 - 421   1996年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOHN WILEY & SONS INC  

    We designed a bioartificial liver support system in which encapsulated multicellular spheroids of rat hepatocytes were utilized as a bioreactor in a hollow fiber cartridge. The spheroids, formed in a positively charged polystyrene dish that contained hormonally defined medium, were encapsulated into microdroplets of agarose that contained about 9 x 10(7) rat hepatocytes. The medium, including 150 mt reservoir volume, was circulated in a closed circuit in which the cartridge was inserted. The pH and levels of dissolved oxygen were monitored and automatically regulated so that they were maintained within a constant range for 72 h. Albumin accumulated in the circuit at the rate of 2.0 mg/L/h in this system. When the bioreactor cells in the system were replaced with Hep G2 cells, a human hepatoblastoma cell line, albumin accumulated at the rate of 0.15 mg/L/h. The spheroids of primary culture hepatocytes had 13 times higher albumin-producing capacity than the aggregates of Hep G2. The serum of a patient with fulminant hepatic failure was circulated in this system with the spheroids of primary culture hepatocytes. The concentration of branched amino acid (BCAA) in the circuit significantly increased during the 48 h circulation, while the concentration of aromatic amino acid (AAA) and methionine decreased. The ratio of BCAA/AAA increased from 0.640 to 0.772, indicating that the hepatocyte spheroids had improved the imbalance of the amino acid profile in the serum. These findings indicate that this system may be a useful model for an artificial liver support. (C) 1996 John Wiley & Sons, Inc.

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  • Detection of hepatitis C virus RNA in circulating immune complexes by RT-PCR 査読

    T Morita, H Hada, N Koide, H Shiraha, T Shinji, M Nakamura, K Ujike, M Wato, H Shimomura, T Tsuji

    HEPATO-GASTROENTEROLOGY43 ( 9 ) 582 - 585   1996年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBL LTD.  

    Background/Aims: We investigate whether hepatitis C virus (HCV) forms a circulating immune complex (CIC) in patients with chronic HCV infection.
    Materials and Methods: We examined HCV-RNA immunoprecipitated with anti-human IgG, A and M antibodies by reverse transcription-polymerase chain I reaction.
    Results: In thirty-nine (91%) of 43 patients, composed of 35 chronic hepatitis (CH) and 8 liver cirrhosis (LC), HCV-RNA was detected in the CIC. All 43 patients analyzed were classified into the following three categories; HCV-RNA was detected only in the supernatant (S pattern, 4 patients), both in the supernatant and the precipitate (SP pattern, 27 patients), and only in the precipitate (P pattern, 12 patients). SP pattern was most common in chronic HCV infection, and the frequency of SP pattern decreased with the progression of Liver disease. P pattern was significantly more frequent in patients with higher gamma-globulin Levels, histologically indicated LC, and antibody to HCV envelope protein.
    Conclusion: We found that HCV formed a CIC in most patients with chronic HCV infection, and that the formation of CIC might be related to the stage of chronic HCV injection.

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  • GENE-EXPRESSION OF LIVER-SPECIFIC PROTEINS IN HEPATOCYTE SPHEROIDS IN PRIMARY CULTURE 査読

    T TAMURA, N KOIDE, H HADA, H SHIRAHA, T TSUJI

    ACTA MEDICA OKAYAMA49 ( 3 ) 161 - 167   1995年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Adult rat hepatocytes assemble to form multicellular spheroids under non-adherent environments such as immobilized chondroitin sulfate-proteoglycan in primary culture. Previously, we demonstrated that hepatocyte spheroids exhibited various differentiated structures as observed in the liver tissue. It was also shown that hepatocyte growth was highly suppressed and several differentiated functions, including albumin production and gluconeogenesis, preserved in spheroids. To investigate differentiated functions of cultured hepatocytes in relation to cell morphology, we compared the expression of the albumin and transferrin genes in spheroids with those in monolayers by Northern blot analysis. Production of these proteins in the culture medium was simultaneously examined by ELISA. Gene expression and protein production of both albumin and transferrin were better preserved in spheroids. We also examined changes in the expression of liver-specific genes in response to IL-6. Reduced mRNA levels of both albumin and transferrin was only found in spheroids and no change was observed in monolayers. These results suggest that the regulation of tissue-specific gene expression is better preserved in spheroids, in which hepatocytes are in close contact with each other.

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  • Diagnostic Accuracy of Laparoscopic Liver Biopsy in Chronic Liver Diseases, Comparison of Laparoscopic and US‐Guided Liver Biopsy Results 査読

    Toshio ITO, Minora UKIDA, Kazuhide YAMAMOTO, Haruhiko KOBASHI, Youichi MORIMOTO, Masayuki MIKAMI, Masaki OMOTO, Sousuke NAKANISHI, Kanji SHINMEN, Takuya NAGANO, Seiji MATSUMOTO, Masaki NAKAMURA, Ryoichi OKAMOTO, Shin‐ichi FUJIOKA, Nobuhiko OMORI, Kozo UJIKE, Hidenori SHIRAHA, Takao TSUJI

    Digestive Endoscopy7 ( 3 ) 261 - 265   1995年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Liver biopsies were carried out using three different needles, a Vim‐Silverman needle 2.5 mm in outer caliber, an 18‐Gauge (18G) Majima needle, and a 17‐Gauge (17G) Majima needle. The biopsies were obtained from nearby locations on the liver surface under laparoscopic observation, to ascertain differences in histological diagnosis according to the size of the biopsy specimen. The biopsy specimens obtained with the Vim‐Silverman needle were wider than those obtained with the other two needles. The agreement in histological diagnoses of the liver, obtained with the Vim‐Silverman needle versus the 18G Majima needle, was 26.0%, while that between the Vim‐Silverman needle and the 17G Majima needle was 40.0%. Histological diagnosis tended to be underestimated in small biopsy specimens in advanced chronic liver diseases. A questionnaire survey, conducted in 92 hospitals affiliated with Okayama University Medical School, revealed US‐guided liver biopsy to be the practice of choice in 57 of 92 (62.0%) hospitals, and 18G needles were used in US‐guided liver biopsy in 35 of 78 (45.2%) hospitals. Copyright © 1995, Wiley Blackwell. All rights reserved

    DOI: 10.1111/j.1443-1661.1995.tb00172.x

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▼全件表示

MISC

  • 肝疾患の診断と治療 生体肝移植後経過より再考する肝硬変合併肺病変の評価

    大山 淳史, 高木 章乃夫, 安中 哲也, 足立 卓哉, 和田 望, 坂田 雅浩, 大西 秀樹, 白羽 英則, 吉田 龍一, 楳田 祐三, 中村 一文, 八木 孝仁, 岡田 裕之

    日本消化器病学会四国支部例会プログラム・抄録集111回   47 - 47   2019年6月

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    記述言語:日本語   出版者・発行元:日本消化器病学会-四国支部  

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  • 肝細胞癌根治的治療後の無再発に寄与する因子としての酸化ストレスの重要性

    室 泰子, 高木 章乃夫, 中村 進一郎, 大山 淳史, 足立 卓哉, 和田 望, 安中 哲也, 大西 秀樹, 白羽 英則, 岡田 裕之

    肝臓60 ( Suppl.1 ) A533 - A533   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌に対する定位放射線治療の有用性

    大西 秀樹, 高木 章乃夫, 能祖 一裕, 大山 淳史, 足立 卓哉, 和田 望, 坂田 雅浩, 安中 哲也, 池田 房雄, 白羽 英則, 岡田 裕之

    肝臓60 ( Suppl.1 ) A377 - A377   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Immuno-Oncology時代の消化器がん診療 難治性消化器癌に対するREIC/Dkk-3遺伝子治療

    内田 大輔, 白羽 英則, 岡田 裕之

    日本消化器病学会雑誌116 ( 臨増総会 ) A113 - A113   2019年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 当院でのレゴラフェニブ使用症例の経過と効果症例の特徴

    足立 卓哉, 能祖 一裕, 大山 淳史, 和田 望, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 高木 章乃夫, 岡田 裕之

    The Liver Cancer Journal10 ( Suppl.2 ) 43 - 44   2018年12月

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    記述言語:日本語   出版者・発行元:(株)メディカルレビュー社  

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  • DCV+ASV併用療法でSVR24を達成した5ヵ月後に再燃を認めたC型慢性肝炎の一例

    和田 望, 池田 房雄, 大山 淳史, 足立 卓哉, 坂田 雅浩, 安中 哲也, 大西 秀樹, 白羽 英則, 高木 章乃夫, 岡田 裕之

    日本消化器病学会中国支部例会プログラム・抄録集110回   119 - 119   2018年12月

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    記述言語:日本語   出版者・発行元:日本消化器病学会-中国支部  

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  • 肝細胞癌に対するシスプラチン肝動注化学療法後に大腸炎を発症した一例

    山本 峻平, 大西 秀樹, 大山 淳史, 足立 卓哉, 和田 望, 坂田 雅浩, 安中 哲也, 池田 房雄, 白羽 英則, 能祖 一裕, 高木 章乃夫, 岡田 裕之

    日本消化器病学会中国支部例会プログラム・抄録集110回   114 - 114   2018年12月

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    記述言語:日本語   出版者・発行元:日本消化器病学会-中国支部  

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  • REIC/Dkk-3遺伝子導入における胆道癌の新規治療法開発

    田中 瑛美, 内田 大輔, 白羽 英則, 加藤 博也, 岡田 裕之

    日本消化器病学会雑誌115 ( 臨増大会 ) A744 - A744   2018年10月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • DAA治療後のSVR後発癌の特徴

    和田 望, 竹内 康人, 池田 房雄, 大山 淳史, 足立 卓哉, 安中 幸, 安中 哲也, 大西 秀樹, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓59 ( Suppl.2 ) A672 - A672   2018年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 進行肝細胞癌におけるソラフェニブ治療の長期生存症例と短期終了症例のそれぞれの特徴

    足立 卓哉, 能祖 一裕, 大山 淳史, 和田 望, 安中 幸, 竹内 康人, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 高木 章乃夫, 高口 浩一, 植松 周二, 高畠 弘行, 萩原 宏明, 岡田 裕之

    The Liver Cancer Journal ( Suppl.1 ) 77 - 77   2018年6月

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    記述言語:日本語   出版者・発行元:(株)メディカルレビュー社  

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  • 5-FU代謝酵素による膵癌化学療法FORFILINOXの効果予測因子の検討

    伊藤 由佳子, 堀口 繁, 柄田 佐和子, 河渕 真治, 加藤 博也, 白羽 英則, 栄田 敏之

    TDM研究35 ( 2 ) 124 - 124   2018年5月

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    記述言語:日本語   出版者・発行元:(一社)日本TDM学会  

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  • エンテカビル投与後のB型肝硬変患者の長期予後

    坂口 智紘, 竹内 康人, 和田 望, 安中 幸, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 高木 章乃夫, 岡田 裕之

    日本消化器病学会雑誌115 ( 臨増総会 ) A390 - A390   2018年4月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 肝がんの分子機構の解明に基づく新規治療法の開発 原発性及び転移性肝癌をターゲットとした新規遺伝子治療

    大山 淳史, 白羽 英則, 岡田 裕之

    日本消化器病学会雑誌115 ( 臨増総会 ) A172 - A172   2018年4月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 肝臓 治療 安全かつ確実なRFA治療を目指した超音波技術の工夫 RFAにおける部分的free-hand法の利点と、ファントムを用いた穿刺トレーニング

    中村 進一郎, 竹内 康人, 能祖 一裕, 大西 秀樹, 森井 和彦, 和田 望, 安中 幸, 白羽 英則, 高木 章乃夫, 岡田 裕之

    超音波医学45 ( Suppl. ) S329 - S329   2018年4月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 非アルコール性脂肪性肝疾患における酸化ストレス評価と発癌も見据えた最適な抗酸化療法の探索

    足立 卓哉, 高木 章乃夫, 下村 泰之, 大山 淳史, 和田 望, 安中 幸, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 岡田 裕之

    肝臓59 ( Suppl.1 ) A522 - A522   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 転移性肝癌の治療と予後への影響 転移性肝癌に対するAd-REIC遺伝子治療

    白羽 英則, 大山 淳史, 岡田 裕之

    肝臓59 ( Suppl.1 ) A225 - A225   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 膵癌化学療法における治療選択バイオマーカーに関する検討

    柄田 佐和子, 伊藤 由佳子, 河渕 真治, 堀口 繁, 加藤 博也, 白羽 英則, 栄田 敏之

    日本薬学会年会要旨集138年会 ( 4 ) 67 - 67   2018年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

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  • 膵癌化学療法における治療選択バイオマーカーに関する検討

    柄田 佐和子, 伊藤 由佳子, 河渕 真治, 堀口 繁, 加藤 博也, 白羽 英則, 栄田 敏之

    日本薬学会年会要旨集138年会 ( 4 ) 67 - 67   2018年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

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  • HCV関連肝細胞癌の根治後にInterferon-free治療を行った312症例の再発と予後の解析

    中村 進一郎, 能祖 一裕, 岡田 裕之, 大西 秀樹, 白羽 英則, 池田 房雄, 桑木 健志, 安中 哲也, 安中 幸, 竹内 康人, 和田 望, 大山 淳史, 高木 章乃夫, 藤岡 真一, 荒木 康之, 岩堂 昭太, 守本 洋一, 安東 正晴, 守屋 昭男, 萩原 宏明, 金吉 俊彦, 狩山 和也, 谷口 英明, 小橋 春彦, 熊田 卓, 豊田 秀徳, 本村 健太

    肝臓58 ( Suppl.3 ) A812 - A812   2017年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 進行肝細胞癌治療における最新治療:基礎と臨床の立場から REIC/Dkk-3遺伝子導入アデノウイルスベクターを用いた肝癌治療

    大山 淳史, 白羽 英則, 岡田 裕之

    肝臓58 ( Suppl.3 ) A744 - A744   2017年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 酸化ストレスマーカーを指標とした肝硬変体液貯留患者のトルバプタン治療

    足立 卓哉, 高木 章乃夫, 佐藤 秀一, 大山 淳史, 和田 望, 安中 幸, 竹内 康人, 安中 哲也, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 岡田 裕之

    肝臓58 ( Suppl.3 ) A860 - A860   2017年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝生検で診断し得た非典型画像の悪性リンパ腫の1例

    坂口 智紘, 和田 望, 大山 淳史, 竹内 康人, 安中 哲也, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓58 ( Suppl.3 ) A827 - A827   2017年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • DAA治療によるSVR後発癌

    竹内 康人, 池田 房雄, 和田 望, 安中 幸, 安中 哲也, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓58 ( Suppl.2 ) A578 - A578   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝硬変に伴う軽症肺高血圧の病態分類と生体肝移植後生命予後に与える影響

    大山 淳史, 高木 章乃夫, 安中 哲也, 足立 卓哉, 和田 望, 竹内 康人, 大西 秀樹, 中村 進一郎, 白羽 英則, 信岡 大輔, 吉田 龍一, 楳田 祐三, 篠浦 先, 岡田 裕之, 八木 孝仁

    肝臓58 ( Suppl.2 ) A650 - A650   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • トルバプタンによる胸水腹水治療戦略 肝硬変患者の体液貯留に対するトルバプタン効果予測因子としての酸化ストレスマーカーの有用性

    足立 卓哉, 高木 章乃夫, 佐藤 秀一, 大山 淳史, 和田 望, 安中 幸, 竹内 康人, 安中 哲也, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 岡田 裕之

    日本門脈圧亢進症学会雑誌23 ( 3 ) 65 - 65   2017年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • 職域での出張肝臓病教室と同時開催の肝炎検診の意義

    難波 志穂子, 池田 房雄, 下村 泰之, 犬山 奈穂美, 大久保 進之介, 槇田 崇志, 長谷川 祐子, 岩井 賢司, 細羽 章子, 三浦 留美, 藤井 洋輔, 安中 哲也, 竹内 康人, 和田 望, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓58 ( 5 ) 304 - 306   2017年5月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

    出張肝臓病教室では、岡山大学病院の肝疾患サポートチームが職域に出向き、職員全員を対象として肝炎検診受検や肝臓専門機関受診の重要性を説明した。12回の出張肝臓病教室を603人が受講し、アンケート回答に欠損のない565人の回答を分析した。肝臓病で通院中の人は3人(0.5%)、健康診断で今まで肝機能異常を指摘されたことがない人が468人(82.8%)、健康診断で肝臓に関する検査結果を意識してみていない人が263人(46.5%)であった。肝臓病教室を受講して肝炎ウイルス検査を受けようと思った人が300人(53.1%)、既に受けている人が154人(27.3%)で、111人(19.6%)は受けないと回答した。講演が職場の肝臓病に対する偏見や誤解の解消に非常に役立つと思った人が347人(61.4%)、少し役に立つと思った人が208人(36.8%)であった。出張肝臓病教室に参加した306名中288名(94.1%)が肝炎検診を受検し、HBs抗原陽性者3名(1%)、HCV抗体陽性者3名(1%)であった。陽性者6名全員が肝炎専門医療機関を受診した。

    DOI: 10.2957/kanzo.58.304

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  • Prospective evaluation of the factors predicting the prognosis of advanced hepatocellular carcinoma (HCC) patients treated with sorafenib.

    Takuya Adachi, Kazuhiro Nouso, Koji Miyahara, Chihiro Dohi, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Koichi Takaguchi, Shuji Uematsu, Shouta Iwadou, Yoshitaka Takuma, Hiroaki Hagihara, Hiroyuki Takabatake, Akinobu Takaki, Hiroyuki Okada

    JOURNAL OF CLINICAL ONCOLOGY35   2017年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    DOI: 10.1200/JCO.2017.35.15_suppl.e15674

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  • 肝腫瘤に対する穿刺・治療の進歩 穿刺用マイクロコンベックスプローブに求められるもの

    中村 進一郎, 大西 秀樹, 桑木 健志, 竹内 康人, 白羽 英則, 和田 望, 安中 幸, 能祖 一裕, 高木 章乃夫, 岡田 裕之

    超音波医学44 ( Suppl. ) S260 - S260   2017年4月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 肝硬変体液貯留に対するトルバプタンの効果予測因子としての酸化ストレスの重要性

    足立 卓哉, 高木 章乃夫, 佐藤 秀一, 大山 淳史, 下村 泰之, 和田 望, 竹内 康人, 安中 幸, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 岡田 裕之

    肝臓58 ( Suppl.1 ) A407 - A407   2017年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 難治性肝細胞癌に対するREIC/Dkk-3を用いた遺伝子治療

    大山 淳史, 澤原 大明, 内田 大輔, 白羽 英則, 岡田 裕之

    肝臓58 ( Suppl.1 ) A282 - A282   2017年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • PREDICTION OF PROGNOSIS: RETREATMENT WITH TACE ON DEMAND IN PATIENTS WITH HCC

    Nozomu Wada, Kazuhiro Nouso, Shouta Iwado, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    GASTROENTEROLOGY152 ( 5 ) S1174 - S1174   2017年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • SUBCLINICAL PULMONARY HYPERTENSION IS A STRONG RISK OF POST LIVING DONOR LIVER TRANSPLANTATION SURVIVAL FOR LIVER CIRRHOSIS

    Yosuke Saragai, Akinobu Takaki, Yuzo Umeda, Tetsuya Yasunaka, Ryuji Kaku, Kazufumi Nakamura, Takahito Yagi, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Takuya Adachi, Yasuyuki Shimomura, Nozomu Wada, Kenji Kuwaki, Fusao Ikeda, Hideki Onishi, Hidenori Shiraha, Shinichiro Nakamura, Hiroshi Ito, Toshiyoshi Fujiwara, Hiroyuki Okada

    GASTROENTEROLOGY152 ( 5 ) S1122 - S1122   2017年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 肝炎ウイルス検査陽性患者に対する検査報告システムの効果的な運用方法 肝臓専門医受診率向上のさらなる工夫

    下村 泰之, 藤井 洋輔, 池田 房雄, 安中 哲也, 山崎 典子, 笠原 郁子, 犬山 奈穂美, 小山 道弘, 難波 志穂子, 竹内 康人, 和田 望, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓58 ( 8 ) 427 - 434   2017年

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

    非肝臓専門診療科で実施される肝炎ウイルス検査の結果が受検者に適切に説明されるように、当院では2013年に電子カルテ上で検査陽性を知らせるアラートの自動表示システムを導入した。このシステムを利用して担当医が説明した割合は28%と不十分であったため、検査実施診療科了解のもと検査陽性者へ検査報告書を郵送し、検査陽性者への報告率は89%と改善した。肝臓専門医への紹介状と返信用書類を同封、郵送半年後に肝臓専門医受診を確認できていない場合は再送し、肝炎専門医受診把握率は49%から72%に改善した(p<0.001)。検査報告書再送で肝精査の必要性に気づき肝臓専門医を受診し、肝炎治療を受けた症例もあった。肝炎ウイルス検査陽性者への報告を徹底することは肝臓専門医受診率の向上や適切な肝炎治療の受療に有用である。(著者抄録)

    DOI: 10.2957/kanzo.58.427

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  • 肝移植後C型肝炎再発に対するソホスブビル含有治療の有効性

    大山 淳史, 高木 章乃夫, 安中 哲也, 足立 卓哉, 池田 房雄, 和田 望, 竹内 康人, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 弘誠, 杭瀬 崇, 信岡 大輔, 吉田 龍一, 楳田 祐三, 吉田 真理, 有森 千聖, 八木 孝仁, 岡田 裕之

    肝臓58 ( 11 ) 599 - 604   2017年

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

    肝移植後C型肝炎に対するDirect Acting Antivirals(DAA)治療効果を検討した。Genotypelは29症例で、ダクラタスビル+アスナプレビル(DCV+ASV)5例、ソホスブビル+レジパスビル(SOF+LDV)25例(含DCV+ASV無効1例)、Genotype2が2症例でSOF+リバビリン治療を行った。DCV+ASVは5例中4例で治療完遂、3例でSustained viral response(SVR)24を達成。SOF+LDVは全例SVR24を達成、移植後2ヵ月以内の肝炎再燃例も含まれているが問題なく治療完遂可能であった。Genotype2はSVR24を達成。SOF中心レジメンで100%のSVR24達成率であり、移植後早期においても問題なくウイルス駆除達成可能であった。C型肝硬変の肝移植適応評価においてC型肝炎のネガティブインパクトはなくなったと言っても過言ではない。(著者抄録)

    DOI: 10.2957/kanzo.58.599

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  • Low-dose FP療法が奏効した切除不能混合型肝癌の1例

    加藤 小百合, 竹内 康人, 和田 望, 森元 裕貴, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    日本消化器病学会雑誌113 ( 12 ) 2050 - 2056   2016年12月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

    症例は50歳代、女性。肝左葉を占める、肝内多発転移・門脈腫瘍塞栓をともなう混合型肝癌と診断された。肝細胞癌成分が有意と判断し、肝細胞癌に準じた化学療法を導入した。Sorafenib・CDDP肝動注療法では病勢と全身状態の悪化を認めたが、Low-dose FP(LFP)療法は奏効を認め、長期生存が得られている。今回LFP療法が、切除不能な混合型肝癌の治療の選択肢としても有効である可能性が示唆された。(著者抄録)

    DOI: 10.11405/nisshoshi.113.2050

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  • 脊柱側彎症術後上腸間膜動脈症候群を合併した一例

    中村 知子, 中村 進一郎, 勢井 麻梨, 戸田 由佳, 竹内 康人, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕

    超音波医学43 ( 6 ) 784 - 784   2016年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 超音波検査で指摘できた腫瘍内出血を伴った肝細胞癌の1例

    竹内 康人, 勢井 麻梨, 中村 知子, 戸田 由香, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 岡田 裕之

    超音波医学43 ( 6 ) 775 - 775   2016年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 後腹膜神経節細胞腫の二例

    戸田 由香, 中村 進一郎, 勢井 麻梨, 中村 知子, 竹内 康人, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕

    超音波医学43 ( 6 ) 784 - 784   2016年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 肝動注化学療法から分子標的薬への切り替えのタイミング 肝機能と早期治療効果判定の観点から

    大西 秀樹, 能祖 一裕, 中村 進一郎, 和田 望, 安中 幸, 竹内 康人, 安中 哲也, 桑木 健志, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓57 ( Suppl.2 ) A562 - A562   2016年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 乏血性腫瘤におけるEOB-MRIを用いた肝癌の診断手順

    土肥 千紘, 能祖 一裕, 赤穂 宗一郎, 和田 望, 森元 裕貴, 竹内 康人, 桑木 健志, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓57 ( Suppl.2 ) A610 - A610   2016年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • データマイニング手法を用いた非侵襲的肝線維化診断法によるC型肝硬変症例の抽出

    桑木 健志, 中村 進一郎, 安中 幸, 竹内 康人, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 高木 章乃夫, 岡田 裕之

    超音波医学43 ( Suppl. ) S673 - S673   2016年4月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • The Pattern of Recurrence Associated With the Prognosis of the Patients With Hepatocellular Carcinoma After Radiofrequency Ablation

    Shinichiro Nakamura, Kazuhiro Nouso, Hideki Onishi, Kenji Kuwaki, Yasuto Takeuchi, Nozomu Wada, Yuuki Morimoto, Tetsuya Yasunaka, Yuki Yasunaka, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto, Hiroyuki Okada

    GASTROENTEROLOGY150 ( 4 ) S1135 - S1135   2016年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Changes of Immunoglobulin-Bound Glycans in Patients With Gastro-Intestinal Cancers

    Chihiro Dohi, Kazuhiro Nouso, Soichiro Ako, Yuuki Morimoto, Koji Miyahara, Hideaki Kinugasa, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    GASTROENTEROLOGY150 ( 4 ) S614 - S614   2016年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Characteristics of HCC Patients With hTERT Promoter Mutation

    Soichiro Ako, Kazuhiro Nouso, Hideaki Kinugasa, Takuya Adachi, Chihiro Dohi, Yuuki Morimoto, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Shinichi Fujioka, Hiroyuki Okada

    GASTROENTEROLOGY150 ( 4 ) S1152 - S1152   2016年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer

    H. Sawahara, H. Shiraha, D. Uchida, H. Kato, T. Nagahara, M. Iwamuro, J. Kataoka, S. Horiguchi, M. Watanabe, M. Sakaguchi, A. Takaki, K. Nouso, Y. Nasu, H. Kumon, H. Okada

    Cancer Gene Therapy23 ( 8 ) 278 - 283   2016年

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  • 直接作用型抗ウイルス薬によるC型肝炎治療後の線維化評価におけるFibroscanの有用性

    竹内 康人, 中村 進一郎, 勢井 麻梨, 中村 知子, 戸田 由香, 桑木 健志, 大西 秀樹, 白羽 英則, 岡田 裕之

    超音波医学42 ( 6 ) 759 - 759   2015年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • TACE後RFAまでの腫瘍縮小を目指した至適待機期間の探索

    赤穂 宗一郎, 中村 進一郎, 能祖 一裕, 和田 望, 森元 裕貴, 竹内 康人, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓56 ( Suppl.3 ) A954 - A954   2015年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝癌治療の新展開 REIC/Dkk-3遺伝子導入による肝細胞癌治療の検討

    澤原 大明, 白羽 英則, 岡田 裕之

    肝臓56 ( Suppl.3 ) A833 - A833   2015年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • C型肝炎に合併した肝原発MALT lymphomaの一例

    勢井 麻梨, 中村 進一郎, 中村 知子, 戸田 由香, 竹内 康人, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕

    超音波医学42 ( 6 ) 758 - 758   2015年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 乳癌に合併したPEComaの一例

    戸田 由香, 中村 進一郎, 勢井 麻梨, 中村 知子, 竹内 康人, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕

    超音波医学42 ( 6 ) 757 - 757   2015年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 異なる経過をたどった多発肝転移合併脾臓原発血管肉腫の2例

    脇地 一生, 大西 秀樹, 能祖 一裕, 大山 淳史, 足立 卓哉, 下村 泰之, 和田 望, 森元 裕貴, 安中 幸, 竹内 康人, 安中 哲也, 桑木 健志, 池田 房雄, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓56 ( Suppl.3 ) A1122 - A1122   2015年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 虫垂に再発した悪性黒色腫の一例

    中村 知子, 中村 進一郎, 勢井 麻梨, 戸田 由香, 竹内 康人, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕

    超音波医学42 ( 6 ) 763 - 763   2015年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • ソラフェニブ治療による長期生存例の検討

    足立 卓哉, 能祖 一裕, 和田 望, 森元 裕貴, 竹内 康人, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓56 ( Suppl.2 ) A749 - A749   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 門脈圧亢進症の病態と治療 基礎から臨床へ 門脈圧亢進症における心肺機能と酸化ストレスについての検討

    高木 章乃夫, 寺尾 正子, 安中 哲也, 白羽 英則, 中村 進一郎, 麻植 浩樹, 中村 一文, 岡田 裕之

    日本門脈圧亢進症学会雑誌21 ( 3 ) 67 - 67   2015年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • Local Recurrences and Complications After Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma: Analysis Focused on Tumor Locations

    Junichi Toshimori, Kazuhiro Nouso, Shinichiro Nakamura, Nozomu Wada, Yuki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Tetsuya Yasunaka, Hideki Onishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    GASTROENTEROLOGY148 ( 4 ) S1030 - S1030   2015年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 適切なRFAのsafety marginとは? 肝細胞癌に対するラジオ波焼灼療法後の局所再発に寄与する因子と適切なsafety margin

    中村 進一郎, 能祖 一裕, 大西 秀樹, 桑木 健志, 竹内 康人, 白羽 英則, 歳森 淳一, 萩原 宏明, 小林 功幸, 山本 和秀

    超音波医学42 ( Suppl. ) S285 - S285   2015年4月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 腫瘍マーカーの推移から見た肝動注化学療法の早期治療効果予測

    大西 秀樹, 能祖 一裕, 中村 進一郎, 和田 望, 竹内 康人, 桑木 健志, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓56 ( Suppl.1 ) A522 - A522   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • C型慢性肝炎に対するアスナプレビル・ダクラタスビル(第3相治験)の臨床的特徴から看護支援の検討

    難波 志穂子, 池田 房雄, 人部 友, 黒田 智, 千堂 年昭, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓56 ( Suppl.1 ) A505 - A505   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • γセクレターゼ阻害薬による肝細胞癌治療抵抗性の克服

    永原 照也, 白羽 英則, 山本 和秀

    肝臓56 ( Suppl.1 ) A383 - A383   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Adenovirus-Mediated Overexpression of REIC/DKK-3 Inhibits Cell Growth and Induces Apoptosis in Pancreatic Cancer and Hepatocellular Carcinoma

    Sawahara Hiroaki, Hidenori Shiraha, Daisuke Uchida, Hironari Kato, Masami Watanabe, Hiromi Kumon, Yasutomo Nasu, Kazuhide Yamamoto

    GASTROENTEROLOGY148 ( 4 ) S954 - S954   2015年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Serum N-Glycan Profiles in Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas

    Yutaka Akimoto, Kazuhiro Nouso, Hironari Kato, Koji Miyahara, Chihiro Dohi, Yuki Morimoto, Hideaki Kinugasa, Takeshi Tomoda, Naoki Yamamoto, Koichiro Tsutsumi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Maho Amano, Shin-ichiro Nishimura, Kazuhide Yamamoto

    GASTROENTEROLOGY148 ( 4 ) S518 - S518   2015年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Alteration of Serum N-Glycan Profile in Patients With Hepatocellular Carcinoma and Their Clinical Application

    Kazuhiro Nouso, Koji Miyahara, Chihiro Dohi, Yuki Morimoto, Hideaki Kinugasa, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    GASTROENTEROLOGY148 ( 4 ) S1022 - S1022   2015年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • REIC/Dkk-3遺伝子導入による肝細胞癌治療の検討

    澤原 大明, 内田 大輔, 白羽 英則, 永原 照也, 岩室 雅也, 片岡 淳朗, 堀口 繁, 竹内 康人, 桑木 健志, 大西 秀樹, 中村 進一郎, 高木 章乃夫, 能祖 一裕, 山本 和秀

    日本消化器病学会雑誌112 ( 臨増総会 ) A345 - A345   2015年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 【最新肝癌学-基礎と臨床の最新研究動向-】 臨床応用を目指した基礎研究 遺伝子発現抑制 RUNX3(runt-related transcription factor 3)発現低下と癌幹細胞化、EMT(epithelial-mesenchymal transition)

    白羽 英則

    日本臨床73 ( 増刊1 最新肝癌学 ) 422 - 425   2015年1月

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    記述言語:日本語   出版者・発行元:(株)日本臨床社  

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  • 腹部超音波検査で発見されたHepatic adrenal rest tumorの一例

    勢井 麻梨, 中村 進一郎, 中村 知子, 戸田 由香, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学41 ( 6 ) 905 - 905   2014年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 特徴的な造影超音波像を呈したReactive lymphoid hyperplasia(RLH)の一例

    中村 知子, 中村 進一郎, 勢井 麻梨, 戸田 由香, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学41 ( 6 ) 906 - 906   2014年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 縦隔腫瘍に合併した肝細胞腺腫の1例

    戸田 由香, 中村 進一郎, 中村 知子, 勢井 麻梨, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学41 ( 6 ) 906 - 906   2014年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • γ-secretase inhibitorによるNotch経路阻害は膵癌幹細胞を阻害し抗癌剤治療効果を増強する可能性がある

    堀口 繁, 白羽 英則, 内田 大輔, 永原 照也, 片岡 淳朗, 岩室 雅也, 加藤 博也, 高木 章乃夫, 能祖 一裕, 山本 和秀

    日本消化器病学会雑誌111 ( 臨増大会 ) A951 - A951   2014年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 膵/胆道癌の分子標的・免疫と治療応用 REIC/Dkk-3遺伝子による膵癌治療

    内田 大輔, 白羽 英則, 山本 和秀

    日本消化器病学会雑誌111 ( 臨増大会 ) A702 - A702   2014年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 非B非C肝癌の臨床的特徴

    竹内 康人, 能祖 一裕, 和田 望, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓55 ( Suppl.2 ) A633 - A633   2014年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 柿胃石の成分分析における標準物質としての柿渋の有用性

    岩室 雅也, 岡本 裕子, 村田 年弘, 河合 良成, 白羽 英則, 岡田 裕之, 山本 和秀

    岡山医学会雑誌126 ( 2 ) 127 - 131   2014年8月

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    記述言語:日本語   出版者・発行元:岡山医学会  

    柿胃石の成分分析における標準物質としてタンニン酸、柿渋および各種の柿を用い、その有用性を赤外吸収分光法にて検討した。その結果、未精製の柿渋の波形が柿胃石症例の波形に最も近いことが明らかとなった。以上の結果から、未精製の柿渋が柿胃石の成分分析における標準物質として有用であることが示唆された。

    DOI: 10.4044/joma.126.127

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  • 【肝胆膵領域の光学医療;一見に如かず】 肝臓領域の腹腔鏡検査 代表的な肝疾患腹腔鏡アトラス(後世に残る図譜として)

    安中 哲也, 池田 房雄, 下村 泰之, 和田 望, 森元 裕貴, 三宅 康広, 白羽 英則, 高木 章乃夫, 能祖 一裕, 岩崎 良章, 山本 和秀

    肝・胆・膵69 ( 2 ) 169 - 176   2014年8月

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    記述言語:日本語   出版者・発行元:(株)アークメディア  

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  • Loss of runt-related transcription factor 3 induces gemcitabine resistance in pancreatic cancer (vol 7, pg 840, 2013)

    Shigeru Horiguchi, Hidenori Shiraha, Teruya Nagahara, Jyunnro Kataoka, Masaya Ituamuro, Minoru Matsubara, Shinichi Nishina, Hironari Kato, Akinobu Takaki, Kazuhiro Nouso, Takehiro Tanaka, Koichi Ichimura, Takahito Yagi, Kazuhide Yamamoto

    MOLECULAR ONCOLOGY8 ( 5 ) 1054 - 1054   2014年7月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI LTD  

    DOI: 10.1016/j.molonc.2014.03.007

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  • 自己免疫性膵炎と悪性腫瘍についての検討

    堀口 繁, 加藤 博也, 室 信一郎, 野間 康宏, 山本 直樹, 原田 亮, 堤 康一郎, 友田 健, 植木 亨, 白羽 英則, 八木 孝仁, 山本 和秀

    膵臓29 ( 3 ) 644 - 644   2014年6月

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    記述言語:日本語   出版者・発行元:日本膵臓学会  

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  • 膵癌におけるγセクレターゼ阻害剤を用いた幹細胞抑制による抗癌剤増強効果の検討

    堀口 繁, 白羽 英則, 内田 大輔, 永原 照也, 片岡 淳朗, 岩室 雅也, 加藤 博也, 高木 章乃夫, 能祖 一裕, 山本 和秀

    膵臓29 ( 3 ) 553 - 553   2014年6月

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    記述言語:日本語   出版者・発行元:日本膵臓学会  

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  • PNET診療ガイドラインをめぐって 膵神経内分泌腫瘍(PNET)のGrade診断及び悪性度診断における造影CTの有用性の検討

    堀口 繁, 加藤 博也, 室 信一郎, 野間 康宏, 山本 直樹, 原田 亮, 堤 康一郎, 田中 健大, 伏見 総一郎, 藤井 雅邦, 植木 亨, 白羽 英則, 八木 孝仁, 山本 和秀

    膵臓29 ( 3 ) 457 - 457   2014年6月

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    記述言語:日本語   出版者・発行元:日本膵臓学会  

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  • The Efficacy of REIC/DKK-3 Gene Therapy for Pancreatic Cancer

    Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Sigeru Horiguchi, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Kazuhide Yamamoto

    GASTROENTEROLOGY146 ( 5 ) S301 - S301   2014年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 肝疾患の病態と糖鎖抗原の意義 網羅的糖鎖解析による肝細胞癌バイオマーカーの検討

    宮原 孝治, 能祖 一裕, 森元 裕貴, 衣笠 秀明, 和田 望, 竹内 康人, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 三宅 康弘, 中村 進一郎, 白羽 英則, 高木 章乃夫, 天野 麻穂, 西村 紳一郎, 山本 和秀

    肝臓55 ( Suppl.1 ) A154 - A154   2014年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝癌におけるNotchシグナル活性化とその治療ターゲットとしての可能性

    白羽 英則, 片岡 淳朗, 堀口 繁, 岩室 雅也, 永原 照也, 内田 大輔, 仁科 慎一, 竹内 康人, 桑木 健志, 大西 秀樹, 中村 進一郎, 高木 章乃夫, 能祖 一裕, 山本 和秀

    肝臓55 ( Suppl.1 ) A229 - A229   2014年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌は、肝星細胞と液性因子を介したインテラクションにより幹細胞化が進行する

    永原 照也, 白羽 英則, 内田 大輔, 岩室 雅也, 片岡 淳朗, 堀口 繁, 山本 和秀

    日本消化器病学会雑誌111 ( 臨増総会 ) A273 - A273   2014年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • γセクレターゼ阻害剤を用いた膵癌幹細胞治療についての検討

    堀口 繁, 白羽 英則, 内田 大輔, 永原 照也, 岩室 雅也, 片岡 淳朗, 加藤 博也, 高木 章乃夫, 能祖 一裕, 山本 和秀

    日本消化器病学会雑誌111 ( 臨増総会 ) A289 - A289   2014年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 肝動注化学療法からソラフェニブへの変更のタイミング

    大西 秀樹, 能祖 一裕, 中村 進一郎, 和田 望, 森元 裕貴, 竹内 康人, 宮原 孝治, 桑木 健志, 三宅 康広, 白羽 英則, 山本 和秀

    日本消化器病学会雑誌111 ( 臨増総会 ) A274 - A274   2014年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 膵神経内分泌腫瘍のGrade診断における造影CTの有用性と病理学的背景の検討

    堀口 繁, 加藤 博也, 室 信一郎, 野間 康宏, 山本 直樹, 原田 亮, 堤 康一郎, 白羽 英則, 田中 健大, 八木 孝仁, 岡田 裕之, 山本 和秀

    日本消化器病学会雑誌111 ( 臨増総会 ) A290 - A290   2014年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 悪性リンパ腫の非腫瘤性肝浸潤の1例

    戸田 由香, 中村 進一郎, 中村 知子, 勢井 麻梨, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学40 ( 6 ) 666 - 666   2013年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 膵鉤部神経鞘腫の一例

    中村 知子, 中村 進一郎, 勢井 麻梨, 戸田 由香, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学40 ( 6 ) 670 - 670   2013年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 腹部USにて診断に苦慮した炎症性偽腫瘍

    勢井 麻梨, 中村 進一郎, 中村 知子, 戸田 由香, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学40 ( 6 ) 667 - 667   2013年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • Strong hepatitis C virus-specific T-cell immune responses correlate with lower hepatitis activities and donor IL28B major genotype in the early period after living donor liver transplantation

    Ryuichiro Tsuzaki, Akinobu Takaki, Takahito Yagi, Fusao Ikeda, Kazuko Koike, Yoshiaki Iwasaki, Hidenori Shiraha, Yasuhiro Miyake, Hirsohi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Masashi Utsumi, Daisuke Nobuoka, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    HEPATOLOGY58   1048A - 1048A   2013年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

    Web of Science

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  • Prediction of Survival in Patients with Hepatocellular Carcinoma Treated with Sorafenib by Comprehensive Serum Glycan Analysis

    Kazuhiro Nouso, Koji Miyahara, Yuuki Morimoto, Yasuto Takeuchi, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Koichi Takaguchi, Takahisa Sato, Shinpei Sato, Shuntaro Obi, Kazuko Hirose, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    HEPATOLOGY58   1242A - 1242A   2013年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • Frequency of regulatory T cell and HCV antigen specific immune response in recurrent hepatitis C after liver transplantation

    Akinobu Takaki, Masashi Utsumi, Kazuko Koike, Takahito Yagi, Nobukazu Watanabe, Ryuichiro Tsuzaki, Hirsohi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Tetsuya Yasunaka, Hidenori Shiraha, Kazuhide Yamamoto

    HEPATOLOGY58   1178A - 1178A   2013年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

    Web of Science

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  • 血清糖鎖マーカーによる進行肝細胞癌の予後予測

    宮原 孝治, 能祖 一裕, 森元 裕貴, 和田 望, 竹内 康人, 萩原 宏明, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 天野 麻穂, 西村 紳一郎, 山本 和秀

    肝臓54 ( Suppl.2 ) A638 - A638   2013年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • TACE不応症例への治療戦略の検討

    和田 望, 能祖 一裕, 中村 進一郎, 森元 裕貴, 竹内 康人, 安中 哲也, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓54 ( Suppl.2 ) A641 - A641   2013年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • C型慢性肝炎の肝線維化診断における高周波探触子を用いたASQの有用性〜Fib-4 indexとの比較

    桑木 健志, 中村 進一郎, 和田 望, 森元 裕貴, 竹内 康人, 萩原 宏明, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 能祖 一裕, 山本 和秀

    肝臓54 ( Suppl.2 ) A632 - A632   2013年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌遠隔転移と血小板の関係

    森元 裕貴, 能祖 一裕, 和田 望, 竹内 康人, 宮原 孝治, 萩原 宏明, 桑木 健志, 安中 哲也, 大西 秀樹, 三宅 康広, 中村 進一郎, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓54 ( Suppl.2 ) A638 - A638   2013年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 法改正後の肝移植紹介患者の経過より分かる現状の生体と脳死の選択

    高木 章乃夫, 保田 裕子, 八木 孝仁, 安中 哲也, 貞森 裕, 篠浦 先, 楳田 祐三, 白羽 英則, 能祖 一裕, 藤原 俊義, 山本 和秀

    日本門脈圧亢進症学会雑誌19 ( 3 ) 184 - 184   2013年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • 【検査値を読む2013】 肝・胆道機能検査 IV型コラーゲン,IV型コラーゲン・7S

    白羽 英則, 山本 和秀

    内科111 ( 6 ) 1240 - 1240   2013年6月

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    記述言語:日本語   出版者・発行元:(株)南江堂  

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  • 肝細胞癌における上皮間葉転換

    山本 和秀, 白羽 英則

    犬山シンポジウム29回   173 - 175   2013年6月

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    記述言語:日本語   出版者・発行元:(株)メディカルトリビューン  

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  • 血管新生関連サイトカインによる進行肝細胞癌の治療効果・予後予測

    宮原 孝治, 能祖 一裕, 和田 望, 森元 裕貴, 竹内 康人, 萩原 宏明, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 山本 和秀

    The Liver Cancer Journal5 ( 2 ) 140 - 141   2013年6月

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    記述言語:日本語   出版者・発行元:(株)メディカルレビュー社  

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  • 【検査値を読む2013】 肝・胆道機能検査 プロコラーゲンタイプIIIペプチド

    白羽 英則, 山本 和秀

    内科111 ( 6 ) 1241 - 1241   2013年6月

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    記述言語:日本語   出版者・発行元:(株)南江堂  

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  • PIVKA-IIに関する最近の話題と将来展望 PIVKA-IIの海外展開 肝細胞癌におけるカルボキシラーゼ活性低下と細胞接着低下およびEMTとの関連

    白羽 英則

    犬山シンポジウム29回   115 - 120   2013年6月

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    記述言語:日本語   出版者・発行元:(株)メディカルトリビューン  

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  • REIC/Dkk-3遺伝子導入による膵癌治療の検討

    内田 大輔, 白羽 英則, 加藤 博也, 永原 照也, 岩室 雅也, 片岡 淳郎, 堀口 繁, 堤 康一郎, 那須 保友, 公文 裕巳, 山本 和秀

    膵臓28 ( 3 ) 371 - 371   2013年6月

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    記述言語:日本語   出版者・発行元:日本膵臓学会  

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  • ソラフェニブ中止に伴う腫瘍進展に関する検討

    宮原 孝治, 能祖 一裕, 森元 裕貴, 竹内 康人, 和田 望, 萩原 宏明, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 三宅 康広, 中村 進一郎, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓54 ( Suppl.1 ) A115 - A115   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • カルニチン及びビタミンE投与による酸化ストレスとNASH病態改善の関連

    石川 久, 高木 章乃夫, 松下 浩志, 津崎 龍一郎, 小池 和子, 三宅 康広, 白羽 英則, 山本 和秀

    肝臓54 ( Suppl.1 ) A389 - A389   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝癌におけるRUNX3発現低下はNotchシグナルを介し癌幹細胞化とEMTを制御する

    白羽 英則, 片岡 淳朗, 堀口 繁, 岩室 雅也, 永原 照也, 内田 大輔, 仁科 慎一, 高木 章乃夫, 萩原 宏明, 桑木 健志, 大西 秀樹, 中村 進一郎, 能祖 一裕, 山本 和秀

    肝臓54 ( Suppl.1 ) A151 - A151   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 原発性硬化性胆管炎の病態における自然免疫の関与

    松下 浩志, 三宅 康広, 山本 和秀, 池田 房雄, 小池 和子, 白羽 英則, 高木 章乃夫, 能祖 一裕

    日本消化器病学会雑誌110 ( 臨増総会 ) A339 - A339   2013年2月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 肝癌EMTマーカーとしてのPIVKA-II

    白羽 英則, 堀口 繁, 岩室 雅也, 片岡 淳朗, 永原 照也, 内田 大輔, 高木 章乃夫, 萩原 宏明, 桑木 健志, 大西 秀樹, 中村 進一郎, 能祖 一裕, 山本 和秀

    日本消化器病学会雑誌110 ( 臨増総会 ) A387 - A387   2013年2月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • RUNX3欠失はmultidrug resistant protein発現を介してgemcitabine感受性に影響を与える

    堀口 繁, 白羽 英則, 内田 大輔, 永原 照也, 片岡 淳朗, 岩室 雅也, 松原 稔, 加藤 博也, 高木 章乃夫, 能祖 一裕, 八木 孝仁, 山本 和秀

    日本消化器病学会雑誌110 ( 臨増総会 ) A210 - A210   2013年2月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 3D/4Dプローブによる多血性肝腫瘤の造影超音波検査の有用性

    中村 進一郎, 能祖 一裕, 大西 秀樹, 白羽 英則, 桑木 健志, 萩原 宏明, 竹内 康人, 山本 和秀

    日本消化器病学会雑誌110 ( 臨増総会 ) A379 - A379   2013年2月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 貧血を契機に発見され肝硬変に至っていた小児自己免疫性肝炎の1例

    室 信一郎, 安中 哲也, 森元 裕貴, 池田 房雄, 白羽 英則, 高木 章乃夫, 能祖 一裕, 山本 和秀

    肝臓54 ( 10 ) 698 - 704   2013年

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

    症例は15歳男児。高校入学時の検診で貧血を指摘され、近医を受診。血液検査にて肝機能障害を認め、CT検査では肝脾腫、少量腹水を認めた。抗核抗体・抗平滑筋抗体陽性、IgG高値であり前医で自己免疫性肝炎(autoimmune hepatitis:AIH)を強く疑われたため、プレドニゾロン(prednisolone:PSL)20mg/日による治療を開始され、更なる精査目的に当科紹介。エコー下肝生検を施行し、新犬山分類F4A3の肝硬変像とAIHに一致する病理所見を得た。PSL開始後の肝機能の改善が不充分であり、PSL40mg/日への増量やアザチオプリンの併用も試みたが効果不十分であった。さらにメチルプレドニゾロンパルス療法を追加したところ肝機能は改善した。本症例は腹部症状や黄疸はなく貧血を契機にAIHと診断された症例であり、診断時には肝硬変に至っていた貴重な症例と考える。(著者抄録)

    DOI: 10.2957/kanzo.54.698

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  • 【肝癌治療のこれまでと今後-アジアをリードする日本の役割-】 腫瘍マーカーの発現メカニズムから考える肝癌治療の方向性

    白羽 英則

    クリニシアン59 ( 11 ) 1062 - 1068   2012年11月

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    記述言語:日本語   出版者・発行元:エーザイ(株)  

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  • 肝嚢胞に近似した超音波像を呈した肝細胞癌結節

    中村 知子, 中村 進一郎, 勢井 麻梨, 戸田 由香, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学39 ( 6 ) 641 - 642   2012年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 4DプローブにてSonazoid造影超音波検査(4D CE-US)を行った類上皮血管内皮腫(EHE)の1例

    萩原 宏明, 中村 進一郎, 勢井 麻梨, 中村 知子, 戸田 由香, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学39 ( 6 ) 638 - 638   2012年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 造影超音波検査で悪性腫瘍との鑑別が困難であった肝炎症性偽腫瘍の2例

    大西 秀樹, 中村 進一郎, 勢井 麻梨, 中村 知子, 戸田 由香, 萩原 宏明, 桑木 健志, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学39 ( 6 ) 641 - 641   2012年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • Sonazoidを用いたCE-USとfusion image併用下の肝細胞癌ラジオ波治療の有用性

    桑木 健志, 中村 進一郎, 勢井 麻梨, 中村 知子, 戸田 由香, 萩原 宏明, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学39 ( 6 ) 641 - 641   2012年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 多発性嚢胞follow中に超音波検査にて血管肉腫肝転移を疑った一例

    勢井 麻梨, 中村 進一郎, 中村 知子, 戸田 由香, 萩原 宏明, 桑木 健志, 白羽 英則, 大西 秀樹, 能祖 一裕, 山本 和秀

    超音波医学39 ( 6 ) 638 - 638   2012年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 肝臓領域の超音波がん検診へのカテゴリー判定導入の有効性と問題点

    桑木 健志, 竹内 康人, 萩原 宏明, 大西 秀樹, 中村 進一郎, 白羽 英則, 能祖 一裕, 山本 和秀

    日本消化器病学会雑誌109 ( 臨増大会 ) A707 - A707   2012年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 非B非C肝癌の予後及び特徴

    竹内 康人, 能祖 一裕, 萩原 宏明, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 三宅 康広, 高木 章乃夫, 山本 和秀

    肝臓53 ( Suppl.2 ) A765 - A765   2012年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Streptozotocin投与NASH発癌モデルマウスにおける病態進行と水素水投与の有効性の検討

    河合 大介, 高木 章乃夫, 山本 和秀, 中司 敦子, 和田 淳, 玉木 直文, 安中 哲也, 小池 和子, 津崎 龍一郎, 松本 和幸, 三宅 康広, 白羽 英則, 森田 学, 槇野 博史

    日本消化器病学会雑誌109 ( 臨増大会 ) A708 - A708   2012年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 膵癌において、CD44の発現は、RUNX3発現は逆相関する(CD44 expression correlates negatively with runt-related transcription factor 3 in pancreatic ductal adenocarcinoma)

    堀口 繁, 白羽 英則, 内田 大輔, 永原 照也, 岩室 雅也, 片岡 淳朗, 加藤 博也, 高木 章乃夫, 能祖 一裕, 山本 和秀

    日本癌学会総会記事71回   179 - 180   2012年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 肝細胞癌において、MRP発現とEMT進行は相関する(MRP expression correlates with epithelial-mesenchymal transition progression in hepatocellular carcinoma)

    片岡 淳朗, 白羽 英則, 中村 進一郎, 能祖 一裕, 堀口 繁, 岩室 雅也, 永原 照也, 松原 稔, 内田 大輔, 桑木 健志, 萩原 宏明, 大西 秀樹, 山本 和秀

    日本癌学会総会記事71回   144 - 144   2012年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 肝細胞癌において、カルボキシラーゼ活性低下はEMT進行に寄与する(Deactivation of GGCX induced epithelial-mesenchymal transition in hepatocellular carcinoma)

    白羽 英則, 片岡 淳朗, 中村 進一郎, 能祖 一裕, 堀口 繁, 岩室 雅也, 永原 照也, 松原 稔, 内田 大輔, 桑木 健志, 萩原 宏明, 大西 秀樹, 山本 和秀

    日本癌学会総会記事71回   142 - 142   2012年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 肝癌基礎 肝細胞癌において、カルボキシラーゼ活性低下は、SPARC発現を誘導し、細胞接着低下、EMT進行を引き起こす

    白羽 英則, 堀口 繁, 岩室 雅也, 片岡 淳朗, 永原 照也, 高木 章乃夫, 萩原 宏明, 桑木 健志, 大西 秀樹, 中村 進一郎, 能祖 一裕, 山本 和秀

    肝臓53 ( Suppl.1 ) A232 - A232   2012年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • B型肝炎 腹腔鏡検査での赤色紋理は、B型慢性肝炎の肝発癌危険因子である

    安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 藤岡 真一, 小橋 春彦, 山本 和秀

    肝臓53 ( Suppl.1 ) A326 - A326   2012年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝癌基礎 RUNX3発現低下は、肝細胞癌における5-FUとcisplatinの耐性化を誘導する

    片岡 淳朗, 白羽 英則, 永原 照也, 岩室 雅也, 堀口 繁, 松原 稔, 山本 和秀

    肝臓53 ( Suppl.1 ) A228 - A228   2012年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 【マルチモダリティによるAbdominal Imaging 2012 臨床編 注目の診断技術は日常診療を変えるか?】 話題の技術・診断法の臨床応用 超音波ガイド下肝穿刺における新プローブの臨床評価 マイクロコンベックスプローブの有用性について

    中村 進一郎, 大西 秀樹, 白羽 英則, 桑木 健志, 萩原 宏明, 竹内 康人, 能祖 一裕, 山本 和秀

    INNERVISION27 ( 5 ) 82 - 85   2012年4月

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    記述言語:日本語   出版者・発行元:(株)インナービジョン  

    このたび、東芝社から超音波診断装置「Aplio 500(TUS-A500)」(図1)に対応した、改良型マイクロコンベックスプローブ「PVT-382BT」(図2)が発売されることとなった。当科では、肝がんのラジオ波焼灼療法(radiofrequency ablation:RFA)や肝生検に際し、専らマイクロコンベックスプローブを使用している。本稿では、まずマイクロコンベックスプローブが必要な理由について述べ、続いて「PVT-382BT」の開発最終段階試用機の使用経験について紹介する。(著者抄録)

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  • 肝癌臨床 HCV関連肝細胞癌の遺伝子学的成因についての検討

    竹内 康人, 池田 房雄, 森藤 由記, 萩原 宏明, 安中 哲也, 桑木 健志, 三宅 康広, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岩崎 良章, 能祖 一裕, 山本 和秀

    肝臓53 ( Suppl.1 ) A263 - A263   2012年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • RUNX3の欠失はMRP発現を誘導しgemcitabine感受性に影響を与える

    堀口 繁, 白羽 英則, 永原 照也, 片岡 淳朗, 岩室 雅也, 高木 章乃夫, 能祖 一裕, 八木 孝仁, 山本 和秀

    日本消化器病学会雑誌109 ( 臨増総会 ) A335 - A335   2012年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • Streptozotocin投与NASHモデルマウスにおける病態進行と水素水投与の有効性の検討

    河合 大介, 高木 章乃夫, 山本 和秀, 松本 和幸, 石川 久, 津崎 龍一郎, 安中 哲也, 中司 敦子, 小池 和子, 三宅 康広, 白羽 英則, 和田 淳

    日本消化器病学会雑誌109 ( 臨増総会 ) A325 - A325   2012年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 【進行肝細胞癌の治療選択】 門脈腫瘍栓合併肝細胞癌への放射線療法の治療効果

    大西 秀樹, 能祖 一裕, 小林 功幸, 白羽 英則, 中村 進一郎, 三宅 康広, 歳森 淳一, 桑木 健志, 萩原 宏明, 山本 和秀

    消化器内科54 ( 1 ) 110 - 114   2012年1月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

    門脈腫瘍栓合併肝細胞癌に対し動注療法および放射線療法を施行した41例(男36例、女5例、平均65歳)の成績を報告した。対象は肝予備能が比較的保たれ、遠隔転移の合併がないStage IVAが主であった。肝実質内の結節に対する動注療法はlow dose FPが22例、5-FU+CDDP+IFNが8例、5-FU単剤が8例、5-FU+IFNが3例で、放射線療法は動注療法の初回導入時に同時併用し、門脈腫瘍栓の肝門部先端に対して三次元照射(2Gy×25回)を行った。生存期間の中央値(MST)は9.9ヵ月、1年生存率42%であった。門脈腫瘍栓に対する治療効果はCR 2%、PR 42%、SD 49%、PD 7%で、奏効率44%、病勢コントロール率93%、1年後の無増悪率59%であった。肝内結節と門脈腫瘍栓の治療効果別に見ると、いずれも奏効した症例のMSTは12.3ヵ月、門脈腫瘍栓のみ奏効が7.5ヵ月、いずれも無効が6.5ヵ月で、これらの間に有意差が認められた。

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  • 血管新生関連サイトカインによるソラフェニブ効果予測

    宮原 孝治, 能祖 一裕, 友田 健, 小林 沙代, 萩原 宏明, 桑木 健志, 歳森 淳一, 大西 秀樹, 中村 進一郎, 白羽 英則, 山本 和秀

    The Liver Cancer Journal3 ( 4 ) 318 - 319   2011年12月

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    記述言語:日本語   出版者・発行元:(株)メディカルレビュー社  

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  • 核酸アナログ併用下、低用量HBIG・ワクチンによるB型肝炎ウイルスコントロール

    高木 章乃夫, 八木 孝仁, 貞森 裕, 松田 浩明, 安中 哲也, 篠浦 先, 楳田 祐三, 吉田 龍一, 内海 方嗣, 小池 和子, 池田 房雄, 三宅 康広, 白羽 英則, 保田 裕子, 藤原 俊義, 山本 和秀

    移植46 ( 6 ) 660 - 660   2011年12月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 肝細胞癌におけるPIVKA-II産生とEpithelial-Mesenchymal Transition

    白羽 英則, 松原 稔, 堀口 繁, 岩室 雅也, 片岡 淳朗, 永原 照也, 高木 章乃夫, 萩原 宏明, 桑木 健志, 大西 秀樹, 中村 進一郎, 能祖 一裕, 山本 和秀

    肝臓52 ( Suppl.3 ) A839 - A839   2011年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 特異な再発形式を呈しSonazoid造影超音波が診断に有用であった肝細胞癌の1例

    萩原 宏明, 中村 進一郎, 能祖 一裕, 竹内 康人, 松下 浩志, 桑木 健志, 大西 秀樹, 白羽 英則, 山本 和秀

    超音波医学38 ( 6 ) 695 - 696   2011年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • B-modeで描出困難であった自己免疫性肝炎に合併した肝細胞癌の1例

    大西 秀樹, 中村 進一郎, 能祖 一裕, 松下 浩志, 竹内 康人, 萩原 宏明, 桑木 健志, 白羽 英則, 山本 和七

    超音波医学38 ( 6 ) 696 - 696   2011年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 肝内に腫瘤影を認めず、門脈内にのみ腫瘍が進展した肝細胞癌の1例

    桑木 健志, 中村 進一郎, 松下 浩志, 竹内 康人, 萩原 宏明, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学38 ( 6 ) 696 - 696   2011年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 血管新生関連サイトカインによる進行肝細胞癌の治療効果予測

    宮原 孝治, 能祖 一裕, 衣笠 秀明, 竹内 康人, 友田 健, 小林 沙代, 萩原 宏明, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 三宅 康広, 中村 進一郎, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓52 ( Suppl.3 ) A810 - A810   2011年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 腹部超音波(US)下経皮肝生検にて診断しえたc-kit陽性間葉腫瘍の1例

    松下 浩志, 中村 進一郎, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 那須 淳一郎, 能祖 一裕, 山本 和秀

    超音波医学38 ( 6 ) 699 - 699   2011年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • USEFULNESS OF SERUM FUCOSYLATED-HEMOPEXIN AS A BIOMARKER FOR HEPATOCELLULAR CARCINOMA IN JAPANESE PATIENTS

    Sayo Kobayashi, Kazuhiro Nouso, Takeshi Tomoda, Koji Miyahara, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Kazuhide Yamamoto

    HEPATOLOGY54   1417A - 1417A   2011年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • SERUM FOLLISTATIN AS A PROGNOSTIC MARKER FOR HEPATOCELLULAR CARCINOMA

    Kazuhiro Nouso, Takeshi Tomoda, Sayo Kobayashi, Koji Miyahara, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY54   1375A - 1376A   2011年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • NBI(Narrow Band Imaging)による腹腔鏡診断

    安中 哲也, 小橋 春彦, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 山本 和秀

    Gastroenterological Endoscopy53 ( Suppl.2 ) 2613 - 2613   2011年9月

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    記述言語:日本語   出版者・発行元:(一社)日本消化器内視鏡学会  

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  • RUNX3発現低下は、HCCにおける5-FUとcisplatinに対する抗癌剤耐性化を誘導する(Loss of RUNX3 induced resistance against 5-fluorouracil and cisplatin in hepatocellular carcinoma)

    片岡 淳朗, 白羽 英則, 永原 照也, 堀口 繁, 岩室 雅也, 松原 稔, 山本 和秀

    日本癌学会総会記事70回   378 - 378   2011年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 肝細胞癌におけるepithelial-mesenchymal transition制御(The regulatory mechanism for epithelial-mesenchymal transition in hepatocellular carcinoma)

    白羽 英則, 仁科 慎一, 堀口 繁, 片岡 淳朗, 岩室 雅也, 松原 稔, 高岡 伸行, 高木 章乃夫, 大西 秀樹, 中村 進一郎, 能祖 一裕, 山本 和秀

    日本癌学会総会記事70回   256 - 256   2011年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • RUNX3発現低下は、MRP発現を亢進させgemcitabine耐性化を誘導する(Loss of RUNX3 induced gemcitabine resistance via inducing multidrug resistance protein expression in pancreatic cancer)

    堀口 繁, 白羽 英則, 片岡 淳朗, 岩室 雅也, 松原 稔, 八木 孝仁, 山本 和秀

    日本癌学会総会記事70回   150 - 150   2011年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 先天性胆道閉鎖症に対する葛西手術後に肝細胞癌を発症した30歳台前半女性の一例

    太田 茂, 高木 章乃夫, 内海 方嗣, 松田 浩明, 大西 秀樹, 池田 房雄, 三宅 康広, 中村 進一郎, 白羽 英則, 岩崎 良章, 能祖 一裕, 八木 孝仁, 山本 和秀

    肝臓52 ( Suppl.2 ) A614 - A614   2011年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 本学関連病院における急性B型肝炎の実態調査

    安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 小橋 春彦, 藤岡 真一, 岡本 良一, 狩山 和也, 高山 裕基, 宮武 宏和, 守屋 昭男, 高口 浩一, 辰川 匡史, 金吉 俊彦, 坂田 達朗, 高畠 弘行, 守本 洋一, 山田 剛太郎, 山本 和秀

    肝臓52 ( Suppl.2 ) A583 - A583   2011年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝硬変に対するインターフェロン治療 血小板減少を伴うC型慢性肝炎・肝硬変症例へのインターフェロン治療に関するQOL評価の解析

    安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 山本 和秀

    日本門脈圧亢進症学会雑誌17 ( 3 ) 59 - 59   2011年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • Hydrogen Rich Water Prevents Progression of NASH and Accompanying Hepatic Tumorigenesis in Mice

    Daisuke Kawai, Akinobu Takaki, Tetsuya Yasunaka, Kazuko Koike, Yasuhiro Miyake, Hidenori Shiraha, Kazuhide Yamamoto

    GASTROENTEROLOGY140 ( 5 ) S703 - S703   2011年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 非アルコール性脂肪性肝炎(NASH)モデルマウスの病態進行に対する水素水の効果の検討

    河合 大介, 高木 章乃夫, 松本 和幸, 津崎 龍一郎, 安中 哲也, 中司 敦子, 小池 和子, 三宅 康広, 白羽 英則, 和田 淳, 山本 和秀

    肝臓52 ( Suppl.1 ) A259 - A259   2011年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 膵臓癌においてRUNX3の発現低下は上皮間葉移行を促進し予後を悪化させる可能性がある

    堀口 繁, 白羽 英則, 片岡 淳朗, 松原 稔, 仁科 慎一, 河本 博文, 八木 孝仁, 山本 和秀

    日本消化器病学会雑誌108 ( 臨増総会 ) A217 - A217   2011年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 劇症肝炎患者の血清中における血管増殖因子レベルと予後

    高山 裕基, 三宅 康広, 能祖 一裕, 安中 哲也, 池田 房雄, 白羽 英則, 高木 章乃夫, 岩崎 良章, 小橋 春彦, 山本 和秀

    肝臓52 ( 3 ) 220 - 220   2011年3月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 【早期肝細胞癌の診断ストラテジー】 早期肝細胞癌診断におけるGd-EOB-DTPA造影MRIの有用性

    中村 進一郎, 能祖 一裕, 小林 功幸, 白羽 英則, 大西 秀樹, 歳森 淳一, 桑木 健志, 萩原 宏明, 高山 裕基, 山本 和秀

    消化器内科51 ( 5 ) 531 - 535   2010年11月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

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  • ラジオ波焼灼療法直後の穿刺部出血の診断と処置に造影超音波検査が有用であった1例

    桑木 健志, 小林 功幸, 中村 進一郎, 高山 裕基, 萩原 宏明, 歳森 淳一, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学37 ( 6 ) 686 - 686   2010年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 肝細胞特異的造影剤Gd-EOB-DTPA造影MRIで検出される乏血性肝細胞性結節の超音波像

    歳森 淳一, 小林 功幸, 中村 進一郎, 高山 裕基, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学37 ( 6 ) 676 - 676   2010年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 原発性胆汁性肝硬変に合併した悪性リンパ腫の一例

    大西 秀樹, 小林 功幸, 中村 進一郎, 高山 裕基, 萩原 宏明, 桑木 健志, 歳森 淳一, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学37 ( 6 ) 678 - 678   2010年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 腹部エコーにて診断し得た径10mm以下のFNHの3症例

    萩原 宏明, 小林 功幸, 中村 進一郎, 高山 裕基, 桑木 健志, 歳森 淳一, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学37 ( 6 ) 677 - 677   2010年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 【これだけは知っておきたい検査のポイント】 免疫学的検査 感染関連検査<ウイルス関連検査> B型肝炎ウイルス関連検査

    白羽 英則, 小出 典男

    Medicina47 ( 11 ) 376 - 378   2010年10月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

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  • 【これだけは知っておきたい検査のポイント】 血液生化学検査 酵素および関連物質 AST(GOT), ALT(GPT)

    白羽 英則, 小出 典男

    Medicina47 ( 11 ) 180 - 181   2010年10月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

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  • 肝疾患(悪性腫瘍を含む)での間質実質相互作用、形質転換からみた治療戦略 HCCにおいてDes-gamma-carboxy prothrombinは腫瘍血管新生に関与する

    松原 稔, 白羽 英則, 山本 和秀

    日本消化器病学会雑誌107 ( 臨増大会 ) A709 - A709   2010年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • RUNX3は膵臓癌細胞において癌細胞の増殖・浸潤能を低下させる

    堀口 繁, 白羽 英則, 岩室 雅也, 片岡 淳朗, 松原 稔, 仁科 慎一, 河本 博文, 八木 孝仁, 山本 和秀

    日本消化器病学会雑誌107 ( 臨増大会 ) A943 - A943   2010年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 癌抑制遺伝子RUNX3はNotchシグナルを抑制しEpCAM陽性肝細胞癌を減少させる

    仁科 慎一, 白羽 英則, 松原 稔, 堀口 繁, 岩室 雅也, 高岡 伸行, 上村 雅之, 萩原 宏明, 桑木 健志, 歳森 淳一, 大西 秀樹, 中村 進一郎, 小林 功幸, 山本 和秀

    日本消化器病学会雑誌107 ( 臨増大会 ) A879 - A879   2010年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 劇症肝炎患者の血清中における血管増殖因子レベルと予後

    高山 裕基, 三宅 康広, 能祖 一裕, 安中 哲也, 池田 房雄, 白羽 英則, 高木 章乃夫, 岩崎 良章, 小橋 春彦, 山本 和秀

    肝臓51 ( Suppl.2 ) A581 - A581   2010年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 進行肝細胞癌に対するソラフェニブ治療

    歳森 淳一, 能祖 一裕, 小林 功幸, 中村 進一郎, 大西 秀樹, 桑木 健志, 萩原 宏明, 白羽 英則, 山本 和秀

    肝臓51 ( Suppl.2 ) A622 - A622   2010年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • RUNX3は肝細胞癌においてJAG1-Notchシグナルを介し癌幹細胞を制御する(RUNX3 expression reduces cancer stem cells in hepatocellular carcinoma through JAG1-Notch signaling repression)

    仁科 慎一, 白羽 英則, 松原 稔, 堀口 繁, 岩室 雅也, 高岡 伸行, 上村 雅之, 片岡 淳朗, 能祖 一裕, 山本 和秀

    日本癌学会総会記事69回   488 - 488   2010年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 肝細胞癌においてDes-gamma-carboxy prothrombinは血管新生に関与する(Des-gamma-carboxy prothrombin is associated with angiogenesis in hepatocellular carcinoma)

    松原 稔, 白羽 英則, 片岡 淳朗, 岩室 雅也, 堀口 繁, 仁科 慎一, 高岡 伸行, 上村 雅之, 能祖 一裕, 山本 和秀

    日本癌学会総会記事69回   130 - 130   2010年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 肝癌においてカルボキシラーゼ活性は、EMTを制御する(Gamma-glutamyl-carboxylase regulates epithelial-mesenchymal transition in hepatocellular carcinoma)

    白羽 英則, 仁科 慎一, 松原 稔, 堀口 繁, 片岡 淳朗, 岩室 雅也, 高岡 伸行, 上村 雅之, 高木 章乃夫, 能祖 一裕, 山本 和秀

    日本癌学会総会記事69回   120 - 120   2010年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • DES-GAMMA-CARBOXY PROTHROMBIN AND ANGIOGENESIS IN HEPATOCELLULAR CARCINOMA

    H. Shiraha, S. Nishina, M. Matsubara, S. Horiguchi, M. Iwamuro, J. Kataoka, N. Takaoka, A. Takaki, K. Nouso, K. Yamamoto

    TUMOR BIOLOGY31   S93 - S93   2010年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:SPRINGER  

    Web of Science

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  • 高齢者肝疾患の治療適応と予後、何歳まで治療するべきか? 高齢者肝細胞癌の治療成績

    能祖 一裕, 小林 功幸, 中村 進一郎, 宮原 孝治, 友田 健, 小林 沙代, 高山 裕基, 大西 秀樹, 歳森 淳一, 萩原 宏明, 桑木 健志, 安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 山本 和秀

    日本高齢消化器病学会誌13 ( 1 ) 89 - 89   2010年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本高齢消化器病学会  

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  • 自己免疫性肝疾患研究の進歩 CTLA4遺伝子の+49A/G多型は自己免疫性肝炎および原発性胆汁性肝硬変の疾患感受性に関連する

    三宅 康広, 安中 哲也, 池田 房雄, 中村 進一郎, 白羽 英則, 小林 功幸, 高木 章乃夫, 岩崎 良章, 能祖 一裕, 小橋 春彦, 山本 和秀

    肝臓51 ( Suppl.1 ) A58 - A58   2010年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞特異的造影剤Gd-EOB-DTPA造影MRIで検出される乏血性肝細胞性小結節の超音波像

    歳森 淳一, 小林 功幸, 中村 進一郎, 大西 秀樹, 桑木 健志, 萩原 宏明, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学37 ( Suppl. ) S495 - S495   2010年4月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • AFP20ng/mL以下の肝細胞癌におけるL3分画測定の意義

    能祖 一裕, 小林 功幸, 中村 進一郎, 高山 裕基, 小林 沙代, 大西 秀樹, 歳森 淳一, 萩原 宏明, 桑木 健志, 安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 岩崎 良章, 小橋 春彦, 山本 和秀

    肝臓51 ( Suppl.1 ) A203 - A203   2010年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌の分子標的探索と臨床応用 RUNX3欠損による肝癌のシグナル活性化

    白羽 英則, 仁科 慎一, 山本 和七

    肝臓51 ( Suppl.1 ) A34 - A34   2010年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 慢性肝炎・肝硬変・肝細胞癌症例における末梢血酸化ストレス度・抗酸化ストレス度の検討

    高木 章乃夫, 玉木 直文, 小池 和子, 安中 哲也, 岩崎 良章, 池田 房雄, 三宅 康広, 白羽 英則, 小橋 春彦, 森田 学, 山本 和秀

    肝臓51 ( Suppl.1 ) A181 - A181   2010年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 異常プロトロンビンの血管新生促進効果の検討

    白羽 英則, 松原 稔, 山本 和秀, 藤川 達也, 仁科 慎一, 堀口 繁, 上村 雅之, 高木 章乃夫, 萩原 宏明, 桑木 健志, 歳森 淳一, 大西 秀樹, 中村 進一郎, 小林 功幸, 能祖 一裕

    日本消化器病学会雑誌107 ( 臨増総会 ) A265 - A265   2010年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 消化器疾患と樹状細胞 病態の解明と治療法の開発 C型肝炎ウイルス(HCV)構成遺伝子導入およびHCVタンパク添加による樹状細胞機能の変化

    高木 章乃夫, 小池 和子, 安中 哲也, 三宅 康広, 白羽 英則, 岩崎 良章, 山本 和秀

    消化器と免疫 ( 46 ) 59 - 63   2010年3月

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    記述言語:日本語   出版者・発行元:日本消化器免疫学会  

    【目的】HCV構成タンパクを健常者樹状細胞に添加した場合の、細胞表面マーカー・サイトカイン産生能の変化を検討した。【方法】健常成人末梢血よりCD14陽性細胞を回収。樹状細胞を樹立後、HCV構成タンパクを添加。細胞表面マーカーの発現を比較、また自己CD4陽性T細胞と、PPDを加えて抗原特異的リンパ球増殖能、および、Th1・Th2・Th17サイトカイン産生の測定を行った。【結果】CD86発現、IFNγ産生・IL17産生はNS4添加により低下したが、成熟刺激により回復した。【結論】HCV-NS4により樹状細胞のTh1産生能・Th17産生能が低下する。(著者抄録)

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  • 男性同性愛者のインターネット・コミュニティを介してGenotype AのB型急性肝炎と大腸アメーバ症を合併感染したと考えられる2症例

    小橋 春彦, 安中 哲也, 池田 房雄, 恩地 正浩, 三宅 康広, 白羽 英則, 高木 章乃夫, 岩崎 良章, 山本 和秀

    日本消化器病学会雑誌107 ( 臨増総会 ) A405 - A405   2010年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 肝細胞特異的造影剤Gd-EOB-DTPA造影MRIのみで検出された乏血性肝細胞性結節の超音波像

    歳森 淳一, 小林 功幸, 中村 進一郎, 高山 裕基, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学36 ( 6 ) 700 - 700   2009年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 小型腫瘤形成型肝内胆管癌の2例

    桑木 健志, 小林 功幸, 中村 進一郎, 高山 裕基, 萩原 宏明, 歳森 淳一, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学36 ( 6 ) 702 - 702   2009年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 肝細胞癌のラジオ波焼灼療法後の局所再発の超音波所見

    大西 秀樹, 小林 功幸, 中村 進一郎, 高山 裕基, 萩原 宏明, 桑木 健志, 歳森 淳一, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学36 ( 6 ) 701 - 701   2009年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 肝腫瘍に対するSonazoid造影下RFA症例の検討

    萩原 宏明, 小林 功幸, 中村 進一郎, 高山 裕基, 桑木 健志, 歳森 淳一, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    超音波医学36 ( 6 ) 701 - 701   2009年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 低用量HBIG・核酸アナログ併用によるHBV関連肝移植症例のHBV再発予防療法における血清HBcrAg、肝組織中HBV DNAの検討

    安中 哲也, 高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松田 浩明, 篠浦 先, 吉田 龍一, 内海 方嗣, 小池 和子, 河合 大介, 池田 房雄, 三宅 康広, 白羽 英則, 小橋 春彦, 山本 和秀

    肝臓50 ( Suppl.3 ) A733 - A733   2009年10月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • LOW-DOSE HEPATITIS B IMMUNOGLOBULIN AND NUCLEOS(T)IDE ANALOGUES THERAPY FOR POST-TRANSPLANTATION HEPATITIS B RESULTS IN LOW INTRAHEPATIC CCCDNA AND SERUM HBCRAG LEVELS

    Tetsuya Yasunaka, Akinobu Takaki, Takahito Yagi, Masashi Utsumi, Ryuichi Yoshida, Daisuke Sato, Fusao Ikeda, Yasuhiro Miyake, Susumu Shinoura, Hidenori Shiraha, Hiroaki Matsuda, Hiroshi Sadamori, Yoshiaki Iwasaki, Kazuhiro Nouso, Haruhiko Kobashi, Kazuhide Yamamoto

    HEPATOLOGY50 ( 4 ) 552A - 552A   2009年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

    Web of Science

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  • 腹腔鏡でびまん性肝紫斑症の所見を呈した肝血管肉腫の1例

    安中 哲也, 小橋 春彦, 萩原 宏明, 桑木 健志, 歳森 淳一, 大西 秀樹, 池田 房雄, 三宅 康広, 白羽 英則, 中村 進一郎, 小林 功幸, 高木 章乃夫, 岩崎 良章, 能祖 一裕, 山本 和秀

    肝臓50 ( Suppl.3 ) A764 - A764   2009年10月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝線維化・発癌機構の解明 癌抑制遺伝子RUNX3は肝細胞癌のapoptosisを亢進させ、移動能を抑制する

    仁科 慎一, 白羽 英則, 山本 和秀

    日本消化器病学会雑誌106 ( 臨増大会 ) A708 - A708   2009年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 肝癌に対するラジオ波焼灼療法における合併症の危険因子の検討 治療関連因子を中心に

    桑木 健志, 小林 功幸, 中村 進一郎, 萩原 宏明, 歳森 淳一, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    肝臓50 ( Suppl.2 ) A573 - A573   2009年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 核酸アナログによりB型肝炎ウイルス関連肝細胞癌の予後は改善されている

    能祖 一裕, 小林 功幸, 中村 進一郎, 大西 秀樹, 歳森 淳一, 萩原 宏明, 桑木 健志, 安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 岩崎 良章, 山本 和秀

    肝臓50 ( Suppl.2 ) A560 - A560   2009年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Von Hippel-Lindau病の10例における膵合併症の検討

    岩室 雅也, 白羽 英則, 河本 博文, 石田 悦嗣, 山本 和秀

    日本消化器病学会雑誌106 ( 臨増大会 ) A925 - A925   2009年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 肝細胞癌における異常プロトロンビン血管新生亢進作用(Des-gamma-carboxy prothrombin promotes growth and angiogenesis in hepatocellular carcinoma)

    白羽 英則, 田中 盛富, 仁科 慎一, 松原 稔, 堀口 繁, 藤川 達也, 高岡 伸行, 上村 雅之, 高木 章乃夫, 山本 和秀

    日本癌学会総会記事68回   312 - 312   2009年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 肝細胞癌においてRUNX3発現低下がJAG1発現を誘導する(The decreased expression of runt-related transcription factor 3 causes jagged-1 expression in hepatocellular carcinoma)

    仁科 慎一, 白羽 英則, 中西 豊, 田中 盛富, 松原 稔, 高岡 伸行, 上村 雅之, 堀口 繁, 山本 和秀

    日本癌学会総会記事68回   315 - 315   2009年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • Diagnosis of Hypovascular Hepatocellular Carcinoma: Evaluated with Gd-EOB-DTPA-Enhanced Liver Magnetic Resonance Imaging

    Shinichiro Nakamura, Yoshiyuki Kobayashi, Kazuhiro Nouso, Hidenori Shiraha, Hiroaki Hagihara, Junichi Toshimori, Kenji Kuwaki, Hideki Ohnishi, Kazuhide Yamamoto

    GASTROENTEROLOGY136 ( 5 ) A856 - A857   2009年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Web of Science

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  • ガイドライン 内科シリーズ 肝癌診療ガイドライン

    小林 功幸, 中村 進一郎, 大西 秀樹, 歳森 淳一, 桑木 健志, 萩原 宏明, 三宅 康広, 白羽 英則, 能祖 一裕, 八木 孝仁, 田中 紀章, 山本 和秀

    岡山医学会雑誌121 ( 1 ) 41 - 45   2009年4月

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    記述言語:日本語   出版者・発行元:岡山医学会  

    DOI: 10.4044/joma.121.41

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  • 再発肝細胞癌に対する経皮的ラジオ波焼灼療法 治療成績と予後因子の検討

    歳森 淳一, 小林 功幸, 中村 進一郎, 萩原 宏明, 安中 哲也, 桑木 健志, 大西 秀樹, 白羽 英則, 能祖 一裕, 山本 和秀

    肝臓50 ( Suppl.1 ) A357 - A357   2009年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • B型慢性肝炎・肝硬変に対する核酸アナログ療法によるAFPの変化と肝細胞癌スクリーニングにおける診断的意義

    小橋 春彦, 安中 哲也, 池田 房雄, 三宅 康広, 谷口 英明, 白羽 英則, 中村 進一郎, 高木 章乃夫, 小林 功幸, 能祖 一裕, 岩崎 良章, 山本 和秀

    肝臓50 ( Suppl.1 ) A193 - A193   2009年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Gd-EOB-DTPA造影MRIは乏血性の早期肝細胞癌の診断に有用である

    中村 進一郎, 小林 功幸, 能祖 一裕, 白羽 英則, 大西 秀樹, 歳森 淳一, 桑木 健志, 萩原 宏明, 山本 和秀

    肝臓50 ( Suppl.1 ) A125 - A125   2009年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 血管新生因子としての異常プロトロンビン in vivoにおける検討

    白羽 英則, 藤川 達也, 仁科 慎一, 松原 稔, 田中 盛富, 高岡 伸行, 中西 豊, 上村 雅之, 上田 直樹, 高木 章乃夫, 山本 和秀

    肝臓50 ( Suppl.1 ) A303 - A303   2009年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 生体肝移植後C型肝炎症例におけるPD-L2発現の検討

    小池 和子, 高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松田 浩明, 安中 哲也, 三宅 康広, 池田 房雄, 白羽 英則, 小橋 春彦, 能祖 一裕, 山本 和秀

    肝臓50 ( Suppl.1 ) A247 - A247   2009年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Des-γ-carboxy prothrombinは血管内皮細胞の増殖能と移動能を亢進させる

    藤川 達也, 白羽 英則, 山本 和秀

    岡山医学会雑誌121 ( 1 ) 1 - 8   2009年4月

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    記述言語:日本語   出版者・発行元:岡山医学会  

    DOI: 10.4044/joma.121.1

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  • Matrix Metalloproteinase 3阻害による肝線維化抑制

    高岡 伸行, 上村 雅之, 松原 稔, 仁科 慎一, 藤川 達也, 田中 盛富, 中西 豊, 白羽 英則, 高木 章乃夫, 山本 和秀

    日本消化器病学会雑誌106 ( 臨増総会 ) A368 - A368   2009年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 肝細胞癌に対するSonazoid造影下RFA症例の検討

    萩原 宏明, 小林 功幸, 中村 進一郎, 桑木 健志, 歳森 淳一, 栗原 直子, 三宅 康広, 白羽 英則, 山本 和秀

    超音波医学36 ( 1 ) 91 - 92   2009年1月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • Sonazoidによる造影USボリュームデータを用いたRVS併用下でのラジオ波焼灼療法

    歳森 淳一, 中村 進一郎, 小林 功幸, 萩原 宏明, 桑木 健志, 栗原 直子, 三宅 康広, 白羽 英則, 山本 和秀

    超音波医学36 ( 1 ) 92 - 93   2009年1月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 肝癌ラジオ波治療におけるBモードUSボリュームデータを用いたRVSの有用性

    桑木 健志, 小林 功幸, 中村 進一郎, 萩原 宏明, 歳森 淳一, 三宅 康広, 栗原 直子, 白羽 英則, 山本 和秀

    超音波医学36 ( 1 ) 92 - 92   2009年1月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 肝癌の分子標的治療 カルボキシラーゼ異常による血管新生誘導

    白羽 英則, 藤川 達也, 山本 和秀

    肝臓49 ( Suppl.2 ) A423 - A423   2008年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • RUNX3は肝細胞癌の進展を抑制する(RUNX3 regulates development of hepatocellular carcinoma)

    中西 豊, 白羽 英則, 田中 盛富, 仁科 慎一, 藤川 達也, 松尾 則行, 高岡 伸行, 上村 雅之, 高木 章乃夫, 山本 和秀

    日本癌学会総会記事67回   185 - 185   2008年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • twist発現が肝細胞癌の転移・移動能を制御する(Twist expression regulates migration and invasion in hepatocellular carcinoma)

    白羽 英則, 松尾 則行, 田中 盛富, 藤川 達也, 高岡 伸行, 中西 豊, 仁科 慎一, 上村 雅之, 高木 章乃夫, 山本 和秀

    日本癌学会総会記事67回   184 - 184   2008年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • RUNX3の肝細胞癌におけるアポトーシス・転移抑制作用

    中西 豊, 白羽 英則, 仁科 慎一, 松尾 則行, 田中 盛富, 高岡 伸行, 上村 雅之, 山本 和秀

    肝臓49 ( Suppl.1 ) A239 - A239   2008年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Hepatitis B virus DNA in liver tissue and risk for hepatocarcinogenesis in patients with hepatitis C virus-related chronic liver disease: A prospective study

    Mikako Obika, Toshiyuki Shinji, Shin-ichi Fujioka, Hidenori Shiraha, Ryo Terada, Norio Koide

    GASTROENTEROLOGY134 ( 4 ) A807 - A807   2008年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 肝硬変の成因別実態

    庄司 凡, 小橋 春彦, 安中 哲也, 萩 原, 桑木 健志, 歳森 淳一, 宮武 宏和, 白羽 英則, 中村 進一郎, 高木 章乃夫, 小林 功幸, 岩崎 良章, 山本 和秀

    肝臓49 ( Suppl.1 ) A105 - A105   2008年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • カルボキシラーゼ活性低下による肝癌進展

    白羽 英則, 高岡 伸行, 上田 直樹, 藤川 達也, 仁科 慎一, 中西 豊, 田中 盛富, 松尾 則行, 高木 章乃夫, 山本 和秀

    肝臓49 ( Suppl.1 ) A241 - A241   2008年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝腫瘍診断におけるHybrid contrast imagingを用いたSonazoid造影超音波の有用性

    歳森 淳一, 小林 功幸, 中村 進一郎, 萩原 宏明, 安中 哲也, 桑木 健志, 宮武 宏和, 庄司 凡, 白羽 英則, 岩崎 良章, 坂口 孝作

    超音波医学35 ( 2 ) 263 - 263   2008年3月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • Sonazoid造影超音波が存在診断に有用であった肝細胞癌の1例

    萩原 宏明, 小林 功幸, 中村 進一郎, 安中 哲也, 桑木 健志, 歳森 淳一, 宮武 宏和, 庄司 凡, 白羽 英則, 岩崎 良章, 坂口 孝作

    超音波医学35 ( 2 ) 262 - 262   2008年3月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • Gamma-Glutamyl-Carboxylase Regulates Development of Hepatocellular Carcinoma

    Hidenori Shiraha, Tatsuya Fujikawa, Naoki Ueda, Nobuyuki Takaoka, Yutaka Nakanishi, Shigetomi Tanaka, Shin-ichi Nishina, Akinobu Takaki, Kazuhide Yamamoto

    TUMOR BIOLOGY29   41 - 41   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:KARGER  

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  • 血管新生からみた肝細胞癌の発生・進展機構とその臨床への貢献 画像的、病理学的、分子生物学的見地から カルボキシラーゼの肝癌血管新生における意義

    白羽 英則, 藤川 達也, 坂口 孝作

    肝臓48 ( Suppl.2 ) A353 - A353   2007年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Gamma-glutamyl carboxylase活性低下による肝細胞癌転移能の変化

    高岡 伸行, 白羽 英則, 藤川 達也, 上田 直樹, 中西 豊, 松尾 則行, 田中 盛富, 仁科 慎一, 高木 章乃夫, 坂口 孝作

    日本消化器病学会雑誌104 ( 臨増大会 ) A679 - A679   2007年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 結腸癌細胞においてhMLH1の発現減少は5-フルオロウラシル介在性アポトーシスの減少に関連する(Decreased expression of hMLH1 correlates with reduced 5-fluorouracil-mediated apoptosis in colon cancer cells)

    藤田 英行, 加藤 順, 堀井 城一朗, 原田 馨太, 平岡 佐規子, 白羽 英則, 坂口 孝作, 白鳥 康史

    日本癌学会総会記事66回   488 - 488   2007年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • カルボキシラーゼ遺伝子変異による肝癌悪性化(Splice variant of gamma-glutamyl carboxylase contributes progression of hepatocellular carcinoma)

    白羽 英則, 上田 直樹, 藤川 達也, 鈴木 真由美, 高岡 伸行, 中西 豊, 松尾 則之, 田中 盛富, 仁科 慎一, 坂口 孝作, 白鳥 康史

    日本癌学会総会記事66回   504 - 504   2007年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • RUNX3による肝癌細胞株における細胞移動能の抑制(RUNX3 inhibits cell migration in hepatocellular carcinoma cell line)

    田中 盛富, 白羽 英則, 中西 豊, 上田 直樹, 高岡 伸行, 松尾 則行, 仁科 慎一, 藤川 達也, 上村 雅之, 高木 章乃夫, 坂口 孝作

    日本癌学会総会記事66回   139 - 139   2007年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 【PIVKA-IIの新しい展開】 PIVKA-IIの基礎 PIVKA-IIと細胞増殖

    白羽 英則, 藤川 達也, 鈴木 真由美, 坂口 孝作, 白鳥 康史

    肝・胆・膵54 ( 4 ) 477 - 481   2007年4月

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    記述言語:日本語   出版者・発行元:(株)アークメディア  

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  • Decreased expression of Hmlh1 correlates with reduced 5-fluorouracil-mediated apoptosis in colon cancer cells

    Hideyuki Fujita, Jun Kato, Joichiro Horii, Keita Harada, Sakiko Hiraoka, Hidenori Shiraha, Yasushi Shiratori

    GASTROENTEROLOGY132 ( 4 ) A629 - A629   2007年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 腫瘍マーカーの分子機能はどこまで解っているのか 異常プロトロンビンの肝細胞癌進展における役割

    白羽 英則, 藤川 達也, 上田 直樹, 鈴木 真由美, 高岡 伸行, 高木 章乃夫, 坂口 孝作, 白鳥 康史

    日本臨床検査自動化学会会誌32 ( 2 ) 164 - 165   2007年4月

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    記述言語:日本語   出版者・発行元:(一社)日本臨床検査自動化学会  

    異常プロトロンビン(PIVKA-II)は、肝細胞癌に特異性が高い腫瘍マーカーである。Alfa feto protein(AFP)との相関が低く二つを組み合わせることで肝細胞癌のスクリーニングに有用なことから、広く臨床現場で用いられている。特に高感度PIVKA-IIの測定が開始されてからは、肝細胞癌の早期診断に役立つばかりではなく、肝細胞癌の治療およびその予後予測にも用いられている。PIVKA-II陽性の肝細胞癌は予後が不良であることが知られており、PIVKA-II陽性の肝細胞癌は陰性の肝細胞癌と比較して門脈腫瘍塞栓を起こしやすいこと、腫瘍径が大きいことなどが既に報告されている。PIVKA-II陽性の肝細胞癌は、その臨床的特徴と比較して、その分子生物学的メカニズムや、その産生機序などは比較的知られていない。プロトロンビン前駆物質やPIVKA-II、正常プロトロンビンはそのN末端に41アミノ酸から構成されるGlaドメインを持つ。このGlaドメインには10個のグルタミン酸残基が存在している。10個のグルタミン酸残基は、vitamin Kとγ-グルタミルカルボキシラーゼ(GGCX)の働きによりカルボキシル化され、カルシウム結合能を有するγ-カルボキシグルタミン酸へと変化する。しかしながら何らかの原因でカルボキシル化が阻害されるとPIVKA-IIが産生されるようになる。(著者抄録)

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  • カルボキシラーゼ遺伝子異常と肝癌増殖

    白羽 英則, 上田 直樹, 鈴木 真由美, 藤川 達也, 真治 紀之, 坂口 孝作, 白鳥 康史, 小出 典男

    Minophagen Medical Review52 ( 2 ) 144 - 145   2007年3月

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    記述言語:日本語   出版者・発行元:(株)ミノファーゲン製薬  

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  • Des gamma-carboxy prothrombin promotes progression of hepatocellular carcinoma

    Hidenori Shiraha, Tatsuya Fujikawa, Mayumi Suzuki, Naoki Ueda, Nobuyuki Takaoka, Shin-ichi Nishina, Shigetomi Tanaka, Kohsaku Sakaguchi, Yasushi Shiratori

    TUMOR BIOLOGY28   105 - 105   2007年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:KARGER  

    Web of Science

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  • Gamma-glutamyl carboxylase inhibits cell migration in hepatocellular carcinoma cell lines

    Nobuyuki Takaoka, Hidenori Shiraha, Naoki Ueda, Shin-ichi Nishina, Tatsuya Fujikawa, Noriyuki Matsuo, Shigetomi Tanaka, Akinobu Takaki, Kohsaku Sakaguchi, Yasushi Shiratori

    HEPATOLOGY44 ( 4 ) 488A - 489A   2006年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • Hepatitis C virus non-structural protein 4 downregulates differentiation and CD4 T cell stimulatory function of dendritic cells

    Akinobu Takaki, Yoshiaki Iwasaki, Kazuko Koike, Masashi Tatsukawa, Hidenori Shiraha, Kohsaku Sakaguchi, Eiichi Nakayama, Yasushi Shiratori

    HEPATOLOGY44 ( 4 ) 308A - 309A   2006年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • 腫瘍マーカーの分子機能はどこまで解っているのか 異常プロトロンビンの肝細胞癌進展における役割

    白羽 英則, 藤川 達也, 上田 直樹, 鈴木 真由美, 高岡 伸行, 高木 章乃夫, 坂口 孝作, 白鳥 康史

    日本臨床検査自動化学会会誌31 ( 4 ) 352 - 352   2006年9月

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    記述言語:日本語   出版者・発行元:(一社)日本臨床検査自動化学会  

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  • Gamma-glutamyl carboxylase活性低下による肝細胞癌悪性化

    高岡 伸行, 白羽 英則, 藤川 達也, 上田 直樹, 中西 豊, 松尾 則行, 田中 盛富, 仁科 慎一, 高木 章乃夫, 坂口 孝作, 白鳥 康史

    日本癌学会総会記事65回   296 - 296   2006年9月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • B型慢性肝炎の血清中HBV-DNA全長塩基配列の検討 肝線維化の進展とゲノム変異

    辰川 匡史, 高木 章乃夫, 白羽 英則, 小池 和子, 岩崎 良章, 小橋 春彦, 坂口 孝作, 白鳥 康史

    肝臓47 ( Suppl.2 ) A391 - A391   2006年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝移植臨床の最前線 生体部分肝移植後のC型ウイルス肝炎の再燃・再発時におけるHCV特異的免疫応答変化の検討

    高木 章乃夫, 八木 孝仁, 岩崎 良章, 小池 和子, 辰川 匡史, 白羽 英則, 貞森 裕, 松川 啓義, 松田 浩明, 篠浦 先, 楳田 祐三, 田中 紀章, 白鳥 康史

    肝臓47 ( Suppl.1 ) A53 - A53   2006年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Laterally spreading type of colorectal adenoma exhibits a unique methylation phenotype and K-ras mutations

    Sakiko Hiraoka, Jun Kato, Joichiro Horii, Keita Harada, Hideyuki Fujita, Tamiya Morikawa, Hidenori Shiraha, Yasushi Shiratori

    GASTROENTEROLOGY130 ( 4 ) A716 - A716   2006年4月

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  • Double mutation in core promoter region of hepatitis B virus genotype C is associated with an increased risk of hepatocellular carcinoma

    Masashi Tatsukawa, Akinobu Takaki, Kazuko Koike, Hidenori Shiraha, Haruhiko Kobashi, Yoshiaki Iwasaki, Yasushi Shiratori

    GASTROENTEROLOGY130 ( 4 ) A751 - A751   2006年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • B型慢性肝炎 発癌例と非発癌例の血清中HBV-DNA全長塩基配列の相違

    辰川 匡史, 高木 章乃夫, 小池 和子, 白羽 英則, 小橋 春彦, 岩崎 良章, 坂口 孝作, 白鳥 康史

    肝臓47 ( Suppl.1 ) A150 - A150   2006年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 異常プロトロンビンDes-γ-carboxy prothrombinの血管新生亢進作用

    藤川 達也, 白羽 英則, 上田 直樹, 鈴木 真由美, 高岡 伸行, 中西 豊, 白鳥 康史

    肝臓47 ( Suppl.1 ) A87 - A87   2006年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Addition of 5-FU enhances the IFN alpha induced signaling pathway and caspase-8 activities, resulting in marked apoptosis in hepatoma cell lines

    Kazuko Koike, Akinobu Takaki, Masashi Tatsukawa, Hidenori Shiraha, Yoshiaki Iwasaki, Haruhiko Kobashi, Kohsaku Sakaguchi, Yasushi Shiratori

    GASTROENTEROLOGY130 ( 4 ) A832 - A832   2006年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 肝癌発生と進展の分子機構 PIVKA-II増殖刺激ネットワークを介する肝細胞癌進展

    白羽 英則, 鈴木 真由美, 白鳥 康史

    肝臓47 ( Suppl.1 ) A20 - A20   2006年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • GGCX(gamma glutamyl carboxylase)の発現制御による肝癌細胞におけるDCP(Des-gamma carboxy prothrombin)産生能の変化と細胞機能

    上田 直樹, 白羽 英則, 藤川 達也, 鈴木 真由美, 高岡 伸行, 中西 豊, 白鳥 康史

    肝臓47 ( Suppl.1 ) A87 - A87   2006年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌におけるRUNX3とapotosisの関連

    中西 豊, 白羽 英則, 仁科 慎一, 松尾 則行, 田中 盛富, 上田 直樹, 藤川 達也, 高岡 伸行, 白鳥 康史

    日本消化器病学会雑誌103 ( 臨増総会 ) A230 - A230   2006年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • DES-gamma-carboxy prothrombin (DCP) promotes vascular endothelial cell proliferation and migration through VEGFR2-PLC gamma-MAPK signaling pathway

    T. Fujikawa, H. Shiraha, M. Suzuki, N. Ueda, N. Takaoka, Y. Nakanishi, K. Sakaguchi, Y. Shiratori

    JOURNAL OF HEPATOLOGY44   S135 - S135   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE BV  

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  • Des-gamma-carboxy prothrombin is an autologous growth factor for hepatocellular carcinoma

    H. Shiraha, M. Suzuki, T. Fujikawa, N. Ueda, N. Takaoka, Y. Nakanishi, A. Takaki, Y. Shiratori

    JOURNAL OF HEPATOLOGY44   S117 - S117   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE BV  

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  • Novel splicing variant of the vitamin K-dependent gamma-glutamyl carboxylase (GGCX) causes des-gamma-carboxyl prothrombin production in human hepatocellular carcinoma cell lines

    N. Ueda, H. Shiraha, T. Fujikawa, M. Suzuki, N. Takanka, Y. Nakanishi, A. Takaki, Y. Shiratori

    JOURNAL OF HEPATOLOGY44   S109 - S110   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE BV  

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  • Novel splicing variant of the vitamin K-dependent Fa-glutamyl carboxylase (GGCX) in human des-gamma-carboxyl prothrombin producing hepatocellular carcinoma cell lines

    N Ueda, H Shiraha, T Fujikawa, M Suzuki, N Takaoka, A Takaki, S Nakamura, Y Shiratori

    HEPATOLOGY42 ( 4 ) 528A - 528A   2005年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • Des-gamma-carboxy prothrombin (DCP) promotes vascular endothelial cell proliferation and migration through PLC-gamma-MAPK signaling pathway.

    T Fujikawa, H Shiraha, M Suzuki, N Takaoka, N Ueda, K Sakaguchi, Y Shiratori

    HEPATOLOGY42 ( 4 ) 646A - 646A   2005年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • 異常プロトロンビンDCPの血管新生亢進作用に関する検討

    藤川 達也, 白羽 英則, 鈴木 真由美, 上田 直樹, 高岡 伸行, 坂口 孝作, 白鳥 康史

    日本癌学会総会記事64回   42 - 42   2005年9月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • Vitamin K-dependent γ-glutamyl carboxylase(GGCX)の発現制御と肝癌細胞の増殖能との関連

    上田 直樹, 白羽 英則, 藤川 達也, 高岡 伸行, 鈴木 真由美, 仁科 慎一, 坂口 孝作, 白鳥 康史

    日本癌学会総会記事64回   268 - 269   2005年9月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • PIVKA-IIは増殖因子か?

    白羽 英則, 鈴木 真由美, 白鳥 康史

    最新医学60 ( 7 ) 1639 - 1642   2005年7月

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    記述言語:日本語   出版者・発行元:(株)最新医学社  

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  • 肝細胞癌における異常プロトロンビンの増殖制御機構

    白羽 英則, 鈴木 真由美, 藤川 達也, 高岡 伸行, 上田 直樹, 高木 章乃夫, 白鳥 康史

    肝臓46 ( Suppl.1 ) A141 - A141   2005年5月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • C型肝炎ウイルス(HCV)構成遺伝子導入及びHCVタンパク貪食による樹状細胞(DC)表面マーカー及び機能の変化

    高木 章乃夫, 辰川 匡史, 小池 和子, 白羽 英則, 岩崎 良章, 白鳥 康史

    肝臓46 ( Suppl.1 ) A225 - A225   2005年5月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 異常プロトロンビンPIVKA-IIの血管新生亢進作用に関する検討

    藤川 達也, 白羽 英則, 白鳥 康史

    肝臓46 ( Suppl.1 ) A141 - A141   2005年5月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • GGCX(gamma glutamyl carboxylase)の発現抑制による肝癌細胞の増殖能亢進作用

    上田 直樹, 白羽 英則, 藤川 達也, 鈴木 真由美, 高岡 伸行, 中西 豊, 白鳥 康史

    肝臓46 ( Suppl.1 ) A38 - A38   2005年5月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • B型慢性肝炎発癌例と非発癌例の血清中HBV-DNA全長塩基配列の相違

    辰川 匡史, 高木 章乃夫, 白羽 英則, 小池 和子, 藤岡 真一, 岩崎 良章, 白鳥 康史

    肝臓46 ( Suppl.1 ) A190 - A190   2005年5月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 消化器癌におけるcAMPを介したCimetidineのEGF依存性細胞増殖,移動能抑制効果

    藤川 達也, 白羽 英則, 中西 豊, 白鳥 康史

    日本消化器病学会雑誌102 ( 臨増総会 ) A229 - A229   2005年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 肝細胞癌におけるRUNX3の発現とその機能解析

    中西 豊, 白羽 英則, 白鳥 康史

    日本消化器病学会雑誌102 ( 臨増総会 ) A228 - A228   2005年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 骨髄由来万能幹細胞の肝細胞への分化誘導と増殖制御可能な株化細胞の樹立

    白羽 英則

    上原記念生命科学財団研究報告集18   379 - 381   2004年11月

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    記述言語:日本語   出版者・発行元:(公財)上原記念生命科学財団  

    肝細胞は,in vitroで数回しか分裂することができない.老化による細胞分裂寿命は,初代培養肝細胞および万能幹細胞由来肝細胞の両方に共通した問題点である.細胞に遺伝子を導入し,その発現を制御することによって老化細胞の分裂寿命を延長し,バイオ人工肝臓のバイオリアクターを大量に確保するための基礎技術の確立を行った.増殖因子受容体の導入およびRNAiによる遺伝子のノックアウトでは細胞増殖能の増加に成功し,さらに細胞分裂寿命の延長にも成功した.継代延長は最高2回でPDLに換算して,6回の分裂が可能であった.しかし,現在のところでは永久に増殖する細胞は得られていない

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  • Des-gamma-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma.

    T Fujikawa, M Suzuki, H Shiraha, N Takaoka, N Ueda, Y Nakanishi, K Koike, A Takaki, Y Shiratori

    HEPATOLOGY40 ( 4 ) 602A - 603A   2004年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • B型慢性肝炎 発癌例と非発癌例の血清中HBV DNA全長塩基配列の相違

    辰川 匡史, 高木 章乃夫, 白羽 英則, 小池 和子, 藤岡 真一, 岩崎 良章, 白鳥 康史

    肝臓45 ( Suppl.2 ) A451 - A451   2004年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • PIVKA-IIによる細胞増殖シグナルをターゲットとした新しい肝細胞癌治療の検討

    鈴木 真由美, 白羽 英則, 藤川 達也, 白鳥 康史

    日本癌学会総会記事63回   398 - 398   2004年9月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • 消化器再生医療における増殖因子受容体遺伝子導入の効果

    白羽 英則, 白鳥 康史

    肝臓45 ( Suppl.2 ) A509 - A509   2004年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌におけるRUNX3の発現とその機能解析

    中西 豊, 白羽 英則, 上田 直樹, 藤川 達也, 鈴木 真由美, 高岡 伸行, 高木 章乃夫, 白鳥 康史

    日本消化器病学会雑誌101 ( 臨増大会 ) A811 - A811   2004年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 消化器癌におけるCimetidineのEGF依存性細胞増殖,移動能に対する効果

    藤川 達也, 白羽 英則, 鈴木 真由美, 白鳥 康史

    日本癌学会総会記事63回   526 - 526   2004年9月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • インターフェロンα8はα2よりもcaspaseを強く活性化し,抗癌剤による肝細胞癌株アポトーシスを誘導する

    小池 和子, 高木 章乃夫, 辰川 匡史, 白羽 英則, 岩崎 良章, 坂口 孝作, 白鳥 康史

    肝臓45 ( Suppl.2 ) A484 - A484   2004年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 【ウイルス性肝炎 基礎・臨床研究の進歩】 C型肝炎ウイルス(HCV) C型慢性肝炎の治療 IFN治療効果判定基準

    白羽 英則, 岩崎 良章, 白鳥 康史

    日本臨床62 ( 増刊7 ウイルス性肝炎(上) ) 489 - 492   2004年7月

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    記述言語:日本語   出版者・発行元:(株)日本臨床社  

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  • Epidermal growth factor activates m-calpain (calpain II), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation (vol 24, pg 2499, 2004)

    A Glading, RJ Bodnar, IJ Reynolds, H Shiraha, L Satish, DA Potter, HC Blair, A Wells

    MOLECULAR AND CELLULAR BIOLOGY24 ( 13 ) 6116 - 6116   2004年7月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    DOI: 10.1128/MCB.24.13.6116.2004

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  • siRNAを用いた新しい肝細胞癌治療の検討

    鈴木 真由美, 白羽 英則, 藤川 達也, 高岡 伸行, 上田 直樹, 白鳥 康史

    肝臓45 ( Suppl.1 ) A53 - A53   2004年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • cAMP-PKA-calpainシグナル伝達経路をターゲットとした癌転移治療

    白羽 英則, 藤川 達也, 鈴木 真由美, 中西 豊, 白鳥 康史

    日本消化器病学会雑誌101 ( 臨増総会 ) A265 - A265   2004年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • インターフェロンαサブタイプによる肝癌細胞株アポトーシス誘導効果の相違

    高木 章乃夫, 小池 和子, 白羽 英則, 岩崎 良章, 坂口 孝作, 稲葉 二朗, 窪田 規一, 白鳥 康史

    日本免疫学会総会・学術集会記録33   331 - 331   2003年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本免疫学会  

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  • Interferon alpha 8 and 2 show differential activation of apoptosis pathway and growth factor pathway in human hepatoma cell lines.

    A Takaki, K Koike, H Shiraha, Y Iwasaki, K Sakaguchi, N Inaba, K Kubota, Y Shiratori

    HEPATOLOGY38 ( 4 ) 406A - 406A   2003年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO  

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  • PIVKA-II-Metオートクラインループをターゲットとした新しい肝細胞癌治療

    白羽 英則, 鈴木 真由美, 白鳥 康史

    肝臓44 ( Suppl.2 ) A308 - A308   2003年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 原発性胆汁性肝硬変では胆管上皮細胞よりHLA class II遺伝子を発現している-Laser Capture Microdissectionを用いたマイクロアレイ解析

    馬場 伸介, 山本 和秀, 寺田 亮, 箱田 知美, 藤岡 真一, 白羽 英則, 白鳥 康史

    肝臓44 ( Suppl.2 ) A456 - A456   2003年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • C型肝炎ウイルス構成遺伝子導入による樹状細胞HLA及びCostimulatory molecule発現の変化についての検討

    高木 章乃夫, 小池 和子, 白羽 英則, 岩崎 良章, 中山 睿一, 白鳥 康史

    肝臓44 ( Suppl.2 ) A433 - A433   2003年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • プロモーター上流結合部位を介したp53によるIGFBP-3の発現誘導とそのメチル化による阻害

    花房 直志, 白羽 英則, 真治 紀之, 能祖 一裕, 湯本 英一朗, 小野 俊朗, 小出 典男

    日本癌学会総会記事62回   114 - 114   2003年8月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • 【内科キーワード2003】 肝・胆・膵 インターフェロン難治症例

    坂口 孝作, 岩崎 良章, 白羽 英則, 白鳥 康史

    内科91 ( 6 ) 1075 - 1075   2003年6月

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    記述言語:日本語   出版者・発行元:(株)南江堂  

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  • Light Cyclerを用いたreal-time PCR法によるLamivudine未治療例における耐性株の検出

    梅岡 二美, 藤岡 真一, 岩崎 良章, 白羽 英則, 谷口 英明, 朴 成郁, 守屋 昭男, 坂口 孝作, 下村 宏之, 山本 和秀, 白鳥 康史

    肝臓44 ( Suppl.1 ) A34 - A34   2003年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Des-gamma-carboxy prothrombin is an autocrine mitogen for hepatocellular carcinoma

    M Suzuki, H Shiraha, T Fujikawa, N Takaoka, A Takaki, Y Nakanishi, N Ueda, K Koike, K Sakaguchi, Y Shiratori

    GASTROENTEROLOGY124 ( 4 ) A285 - A285   2003年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO  

    Web of Science

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  • インターフェロンαサブタイプによる肝癌細胞アポトーシス誘導能の相違と,細胞内情報伝達系及びアポトーシス関連遺伝子の変化の関連

    高木 章乃夫, 小池 和子, 白羽 英則, 岩崎 良章, 坂口 孝作, 白鳥 康史

    肝臓44 ( Suppl.1 ) A168 - A168   2003年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • ケモカインinterferon-γinducible protein-10の肝線維化に与える影響

    白羽 英則, Alan Wells, 白鳥 康史

    肝臓44 ( Suppl.1 ) A101 - A101   2003年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 再生医療におけるEGF受容体依存性シグナル伝達

    白羽 英則, Wells Alan, 白鳥 康史

    日本消化器病学会雑誌100 ( 臨増総会 ) A230 - A230   2003年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • インターフェロンαサブタイプによる肝癌細胞アポトーシス誘導能の相違 インターフェロンα2とα8で異なる細胞内情報伝達系とアポトーシス関連遺伝子の連係

    高木 章乃夫, 小池 和子, 白羽 英則, 岩崎 良章, 白鳥 康史

    日本消化器病学会雑誌100 ( 臨増総会 ) A150 - A150   2003年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 【発癌のケモプリベンション】 発癌予防

    白羽 英則, 白鳥 康史

    細胞35 ( 3 ) 76 - 77   2003年3月

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    記述言語:日本語   出版者・発行元:(株)ニュー・サイエンス社  

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  • IP-9 induced keratinocyte migration is effected through mu-calpain isoform during wound repair

    L Satish, A Glading, H Shiraha, D Yager, A Wells

    MOLECULAR BIOLOGY OF THE CELL12   43A - 43A   2001年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Web of Science

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  • cAMP-dependent PKA inhibits EGF-induced fibroblast cell motility by directory phosphorylating M-calpain

    H Shiraha, A Glading, ZC Jia, A Wells

    MOLECULAR BIOLOGY OF THE CELL12   2A - 2A   2001年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Web of Science

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  • Epidermal growth factor receptor signaling is decreased in aged fibroblasts

    H Shiraha, K Tran, A Wells

    MOLECULAR BIOLOGY OF THE CELL12   16A - 16A   2001年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Web of Science

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  • Epidermal growth factor (EGF) receptor transcription is decreased in near sensecent human fibroblasts

    H Shiraha, A Wells

    MOLECULAR BIOLOGY OF THE CELL11   457A - 457A   2000年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Web of Science

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  • The ELR-negative CXC chemokines inhibits EGF-induced cell motility by limiting calpain activation

    H Shiraha, A Glading, A Wells

    MOLECULAR BIOLOGY OF THE CELL11   85A - 85A   2000年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Web of Science

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  • 肝癌遺伝子発現のマイクロアレイによる解析

    花房 直志, 湯本 泰弘, 真治 紀之, 白羽 英則, 氏家 浩三, 平崎 照士, 小出 典男, 東 俊宏, 辻 孝夫

    肝臓40 ( Suppl.2 ) 216 - 216   1999年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • ELR-negative CXC chemokines inhibit EGF receptor-induced mobility by decreasing EGF-induced calpain activity.

    H Shiraha, K Gupta, A Glading, A Wells

    AMERICAN JOURNAL OF CLINICAL PATHOLOGY112 ( 1 ) 136 - 136   1999年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLIN PATHOLOGISTS  

    Web of Science

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  • Epidermal growth factor receptor-mediated motility in fibroblasts

    A Wells, K Gupta, P Chang, S Swindle, A Glading, H Shiraha

    MICROSCOPY RESEARCH AND TECHNIQUE43 ( 5 ) 395 - 411   1998年12月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:WILEY-LISS  

    Cell motility is induced by many growth factors acting through cognate receptors with intrinsic tyrosine kinase activity (RPTK). However, most of the links between receptor activation and the biophysical processes of cell motility remain undeciphered. We have focused on the mechanisms by which the EGF receptor (EGFR) actuates fibroblast cell motility in an attempt to define this integrated process in one system. Our working model is that divergent, but interconnected pathways lead to the biophysical processes necessary for cell motility: cytoskeleton reorganization, membrane extension, formation of new adhesions to substratum, cell contraction, and release of adhesions at the rear. We postulate that for any given growth factor some of the pathways/processes will be actively signaled and rate-limiting, while others will be permissive due to background low-level activation. Certain couplings have been defined, such as PLC gamma and actin modifying proteins being involved in cytoskeletal reorganization and lamellipod extension and MEK being implicated in detachment from substratum. Others are suggested by complementary investigations in integrin-mediated motility, including rac in membrane protrusion, rho in new adhesions, myosin II motors in contraction, and calpain in detachment, but have yet to be placed in growth factor-induced motility. Our model postulates that many biochemical pathways will be shared between chemokinetic and haptokinetic motility but that select pathways will be activated only during RPTK-enhanced motility. (C) 1998 Wiley-Liss, Inc.

    Web of Science

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  • Aging fibroblasts present reduced EGF responsiveness due to preferential loss of EGF receptors

    H Shiraha, K Gupta, KA Drabik, A Wells

    MOLECULAR BIOLOGY OF THE CELL9   234A - 234A   1998年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Web of Science

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  • Chemokine IP-10 inhibits EGF-induced fibroblast motility by preventing EGF receptor-mediated cell detachment from substratum

    H Shiraha, K Gupta, A Wells

    MOLECULAR BIOLOGY OF THE CELL9   288A - 288A   1998年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Web of Science

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  • The effect of aging on epidermal growth factor receptor-mediated fibroblast motility and proliferation.

    H Shiraha, K Gupta, A Wells

    MOLECULAR BIOLOGY OF THE CELL8   2230 - 2230   1997年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Web of Science

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  • The effect of ELR-C-X-C chemokines on EGF-induced fibroblast motility.

    A Wells, H Shiraha, K Gupta

    MOLECULAR BIOLOGY OF THE CELL8   2229 - 2229   1997年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Web of Science

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  • ハイブリッド型人工肝臓開発のためのブタ肝細胞の大量調整法の開発

    中村 正基, 小出 典男, 白羽 英則

    人工臓器25 ( 3 ) 674 - 677   1996年6月

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    記述言語:日本語   出版者・発行元:(一社)日本人工臓器学会  

    初代培養肝細胞を用いる生物学的人工肝臓補助装置の開発には,中大動物肝細胞の大量調整法の開発が不可欠である.この論文では,20-25kgのブタから短時間で大量の単離肝細胞を分離する方法を報告した.全身麻酔下で,門脈から前灌流に続いてディスパーゼ 10,000単位添加0.05%コラゲナーゼ液で灌流し,胆嚢剥離後,肝臓を摘出した.摘出肝を37℃に加温しながら,0.05%コラゲナーゼ液で10分間灌流した.これにより,肝小葉断片と多少の単離細胞が得られた.この組織断片浮遊液をメッシュ4.7-100のふるいで分別濾過した.どのようなメッシュサイズの組み合わせでも常にメッシュ30ふるいに多量の肝小葉断片が詰まり貯留した.更にコラゲナーゼ液を追加して,37℃で約10分間軽く振盪することにより容易にふるいを通過した.この方法により,20-25kgのブタより約100gの単離肝細胞が肝灌流開始から約2時間で回収された

    DOI: 10.11392/jsao1972.25.674

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  • 慢性ウイルス性肝疾患における腹腔鏡所見と肝細胞癌発生の関連性

    白羽 英則

    Gastroenterological Endoscopy38 ( Suppl.1 ) 718 - 718   1996年2月

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    記述言語:日本語   出版者・発行元:(一社)日本消化器内視鏡学会  

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  • 比重密度勾配遠心及び固相化lectinを利用したC型肝炎ウイルス粒子表面の糖鎖の解析とウイルス粒子の精製

    白羽 英則

    日本消化器病学会雑誌92 ( 臨増 ) 1483 - 1483   1995年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • ラット肝細胞spheroidをbioreactorとするhollow fiber型人工肝臓の開発

    白羽 英則, 小出 典男, 真治 紀之

    人工臓器24 ( 3 ) 740 - 743   1995年6月

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    記述言語:日本語   出版者・発行元:(一社)日本人工臓器学会  

    培養槽にhollow fiberを用い,bioreactorとしてアガロースのマイクロビーズにカプセル化したラット肝細胞spheroidを用いた生物学的人工肝臓モデルを作成した. 1)培養液のpH,溶存酸素濃度をモニターしフィードバック制御を行うことによってbioreactorの培養条件を自動的に一定に保つことができた. 2)Albuminの産生は培養期間を通じて2.0mg/l/hour,transferrinの産生は培養開始から24時間まで0.84mg/l/hourとよく保たれていた. 3)Bioreactorとした肝細胞spheroidのviabilityは培養前91%,培養後86%とほとんど変化がなく,形態もよく保たれていた

    DOI: 10.11392/jsao1972.24.740

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  • ラット肝細胞スヘェロイドを用いたホローファイバー型人工肝臓モデルの検討

    白羽 英則

    日本消化器病学会雑誌91 ( 臨増 ) 1770 - 1770   1994年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • C型肝炎ウイルス粒子の表面糖鎖の解析

    白羽 英則, 羽田 元, 小出 典男

    消化器と免疫 ( 29 ) 185 - 189   1994年8月

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    記述言語:日本語   出版者・発行元:日本消化器免疫学会  

    C型肝硬変患者の肝組織より超遠心と蔗糖密度勾配遠心によりHCV粒子を調製し,固定化lectin (ConA, LCA, RCA, WGA)を用いたaffinity column chromatographyで分画し,HCV-RNAの検出を行うことによってlectinへの結合能を検討した。蔗糖密度勾配遠心ではdensity 1.14g/mlの分画にHCV-RNAが検出された。WGAには強い親和性を,ConA, RCAには中等度の親和性を示したが,LCAには結合しなかった。これらの結果よりHCV粒子は肝組織より分離できる可能性があること,さらに分離HCV粒子表面の糖鎖は主に複合型糖鎖又は混成型糖鎖である可能性が示唆された

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  • カプセル化したラット肝細胞スフェロイドを用いた人工肝臓モデルでのアルブミンと尿素の産生能に関する検討

    白羽 英則

    肝臓35 ( Suppl.1 ) 155 - 155   1994年6月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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▼全件表示

産業財産権

共同研究・競争的資金等の研究

  • 新規バイオチップを用いた消化器癌の血液循環癌細胞検出

    2020年04月 - 2021年03月

    岡山県健康づくり財団  令和2年度がんに関する研究助成金 

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    担当区分:研究代表者 

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  • 新規ナノバイオチップを用いた消化器がん患者における血中循環腫瘍細胞解析

    2019年07月 - 2020年03月

    岡山大学  令和元年度岡山大学-産総研マッチング研究支援事業 

    白羽 英則

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:500000円

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  • 糖鎖変化による肝癌進展機序の解明

    2019年04月 - 2022年03月

    日本学術振興会  基盤研究(C) 

    大西 秀樹, 大学病院

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    資金種別:競争的資金

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • プロテオーム解析に基づくエクソソームを用いたIPMN良悪性診断法の開発

    2019年04月 - 2022年03月

    日本学術振興会  基盤研究(C) 

    堤 康一郎, 大学病院

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    資金種別:競争的資金

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • REIC遺伝子導入アデノウイルスベクターを用いた肝癌遺伝子治療

    2019年01月 - 2021年12月

    日本消化器病学会  日本消化器病学会臨床研究助成 

    白羽 英則

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:3000000円

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  • 肝細胞癌に対する新規遺伝⼦治療の開発

    2019年01月 - 2019年12月

    エーザイ  医学・薬学に関する研究活動への奨学寄付 

    白羽 英則

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:500000円 ( 直接経費:500000円 )

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  • 消化器癌における新規癌関連遺伝子REICの機能解析と臨床応用に関する研究

    2015年 - 2017年

    岡山大学  基盤研究(C) 

    加藤 博也, 大学病院

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    資金種別:競争的資金

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  • 肝癌における癌悪性化シグナルを標的とした新規治療法の確立

    2015年 - 2017年

    岡山大学  基盤研究(C) 

    白羽 英則, 大学病院

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    担当区分:研究代表者  資金種別:競争的資金

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  • 肝細胞癌化学療法の革新的選択基準開発

    2015年 - 2017年

    岡山大学  基盤研究(C) 

    能祖 一裕, 医学部, 客員研究員

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    資金種別:競争的資金

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  • 肺癌におけるR-spondin-Lgr6シグナル系の発現・機能解析

    2014年 - 2016年

    福岡歯科大学  基盤研究(C) 

    橋本 修一, 口腔歯学部

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    資金種別:競争的資金

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  • miRNA阻害による効率的肝癌動注化学療法の開発

    2014年 - 2016年

    岡山大学  基盤研究(C) 

    中村 進一郎, 大学病院

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    資金種別:競争的資金

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  • 消化器癌における新規癌関連遺伝子REICの機能解析と臨床応用に関する研究

    2012年 - 2014年

    岡山大学  基盤研究(C) 

    加藤 博也, 大学病院

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    資金種別:競争的資金

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  • iPS細胞由来肝細胞を用いた肝不全治療法の確立

    2011年 - 2013年

    岡山大学  基盤研究(C) 

    山本 和秀, 医歯(薬, 学総合研究科

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    資金種別:競争的資金

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  • 肝癌におけるNotchシグナルをターゲットとした新規腫瘍血管新生抑制療法の開発

    2011年 - 2013年

    岡山大学  基盤研究(C) 

    白羽 英則, 大学病院

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    担当区分:研究代表者  資金種別:競争的資金

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  • 新規パラメーターを用いた肝癌化学療法効果予測

    2011年 - 2013年

    岡山大学  基盤研究(C) 

    能祖 一裕, 医歯(薬, 学総合研究科

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    資金種別:競争的資金

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  • 新規循環がん細胞検出による肝細胞癌テーラメード治療法の確立

    2010年 - 2012年

    岡山大学  基盤研究(C) 

    中村 進一郎, 岡山大学病院

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    資金種別:競争的資金

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  • 肝臓組織幹細胞を用いた肝再生療法の開発

    2010年 - 2012年

    岡山大学  基盤研究(C) 

    小出 典男, 医歯(薬, 学総合研究科

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    資金種別:競争的資金

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  • 肝癌進展と血管新生の新規メカニズム

    2008年 - 2010年

    岡山大学  基盤研究(C) 

    白羽 英則, 病院, 助

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    担当区分:研究代表者  資金種別:競争的資金

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