研究者詳細 - 高木　章乃夫

MISC - 高木　章乃夫

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アルコール性肝硬変患者に対する肝移植適応基準確立に向けた岡山大学病院での取組み

吉田龍一, 高木弘誠, 内海方嗣, 信岡大輔, 楳田祐三, 篠浦先, 貞森裕, 保田裕子, 高木章乃夫, 藤原俊義, 八木孝仁

移植 48 ( 総会臨時 ) 309 - 309 2013年8月

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

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

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

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

脂肪性肝疾患における血中Fetuin-Aの検討

岩崎良章, 池田房雄, 安中哲也, 竹内康人, 森藤由記, 森元裕貴, 三宅康広, 高木章乃夫, 山本和秀

肝臓 54 ( Suppl.1 ) A308 - A308 2013年4月

C型慢性肝炎患者におけるインターフェロン治療前AFP値と肝発癌予測

竹内康人, 池田房雄, 安中哲也, 三宅康広, 高木章乃夫, 岩崎良章, 藤岡真一, 大澤俊哉, 宮武和宏, 荒木康之, 牧野泰祐, 谷口英明, 妹尾知典, 高口浩一, 松村周治, 真鍋康二, 山本和秀

肝臓 54 ( Suppl.1 ) A130 - A130 2013年4月

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

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 Gastroenterology 48 ( 3 ) 405 - 412 2013年3月

記述言語：英語

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.

DOI： 10.1007/s00535-012-0647-3

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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

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

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

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

8.NASHに対する水素分子の有用性

高木章乃夫, 山本和秀

Hepatology Practice第二巻 2 ( 2 ) 376 - 379 2013年

Nashに対する水素分子の有用性

河合大介, 高木章乃夫, 山本和秀

岡山医学会雑誌 125 ( 3 ) 201 - 204 2013年

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

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 Oncology 7 ( 4 ) 840 - 849 2013年

記述言語：英語出版者・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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Risk factors for acute renal injury in living donor liver transplantation: evaluation of the RIFLE criteria．国際誌

Utsumi M, Umeda Y, Sadamori H, Nagasaka T, Takaki A, Matsuda H, Shinoura S, Yoshida R, Nobuoka D, Satoh D, Fuji T, Yagi T, Fujiwara T

Transpl Int 26 ( 8 ) 842 - 52 2013年

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

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

BIOMEDICAL ENGINEERING ONLINE 11 e93-e93 2012年12月

記述言語：英語出版者・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.

DOI： 10.1186/1475-925X-11-93

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

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

ACTA MEDICA OKAYAMA 66 ( 6 ) 461 - 468 2012年12月

記述言語：英語出版者・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.

DOI： 10.18926/AMO/49042

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

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 CANCER 131 ( 11 ) 2537 - 2546 2012年12月

記述言語：英語出版者・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.

DOI： 10.1002/ijc.27575

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

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 RESEARCH 42 ( 12 ) 1187 - 1195 2012年12月

記述言語：英語出版者・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.

DOI： 10.1111/j.1872-034X.2012.01044.x

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