Faculty Profiles - ISHIKAWA, Tetsuya

Papers - ISHIKAWA, Tetsuya

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

ISHIKAWA Tetsuya

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

Authorship：Lead author Language：English

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

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

洪繁、松浦俊博、木村宏之、石川哲也、京兼和宏、山田理

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

Language：Japanese Publishing type：Research paper (scientific journal)

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

瀉血による慢性肝炎の進展予防

伊東和樹, 石川哲也

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

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

伊東和樹, 石川哲也

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

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

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

Liver Int page： 1359-1365 2011.6

Language：English Publishing type：Research paper (scientific journal)

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

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

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

葛谷貞二, 竹田欽一, 宇都宮節夫, 多賀雅浩, 川田登, 池田誉, 今井則博, 水谷佳貴, 広瀬健, 石川哲也

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

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(株)癌と化学療法社

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

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

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

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

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

沈降型B型肝炎ワクチン Invited

石川哲也

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

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

PubMed

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

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC IMMUNOLOGISTS

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

DOI： 10.4049/jimmunol.0904173

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

Ito Hiroyasu, Ando Kazuki, Ishikawa Tetsuya, SEISHIMA Mitsuru

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

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

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

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

A case of erythropoietic protoporphyria with severe liver damage Reviewed

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

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

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

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

DOI： 10.2957/kanzo.51.175

Scopus

CiNii Books

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

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

Vol. 37 ( 3 ) page： 527-529 2010.3

B型肝炎に対する免疫療法 Invited

石川哲也

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

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

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

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

Language：Japanese Publishing type：Research paper (scientific journal)

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

PubMed

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

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

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

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

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

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

BSCガストロストミーシステムを用いた胃瘻交換時における患者に与える影響についての検討

綾田穣, 堀田直樹, 中野達徳, 鮫島庸一, 吉田篤生, 花井恵美, 伊藤陽子, 徳永有姫, 石川哲也, 増子和郎

在宅医療と内視鏡治療 Vol. 13 ( 1 ) page： 19 - 24 2009.9

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：PEG・在宅医療研究会

BSCガストロストミーシステム:BSC gastrostomy system(以下BSCGSと略す)は、ガイドワイヤーを用いずに胃瘻造設後のカテーテル交換を行うことができるバンパータイプ・ボタン型カテーテルキットである。今回BSCGSに改良が加えられたため、交換に要する時間や、バイタルサインの変化について、ガイドワイヤーを用いる同タイプのキットとの比較検討を行った。BSCGSでは、有意に交換時間が短縮され(p<0.01)、バイタルサインの変化に有意差は認めず、有用かつ安全と考えられた。(著者抄録)

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

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

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

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Papers - ISHIKAWA, Tetsuya