 | 本庶 元 （ホンジョ ハジメ）
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Last Updated :2024/04/25
コミュニケーション情報 byコメンテータガイド
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消化器全般、内視鏡診断と治療を担当しています。
研究者情報
学位
ホームページURL
科研費研究者番号
- 60845808
ORCID ID
J-Global ID
研究キーワード
- 炎症性腸疾患 消化器内視鏡
現在の研究分野（キーワード）
- 消化器全般、内視鏡診断と治療を担当しています。
研究分野
経歴
- 2022年04月 - 現在 近畿大学医学部 消化器内科医学部講師
- 2019年04月 - 2022年03月 近畿大学医学部 消化器内科助教
- 2009年07月 - 2019年04月 大津赤十字病院消化器内科副部長
- 2003年04月 - 2009年07月 大阪鉄道病院消化器内科医長
- 1998年04月 - 2003年03月 虎の門病院消化器科医員
- 1995年04月 - 1998年03月 城北病院内科研修医
学歴
研究活動情報
論文
- Sho Masaki; Hajime Honjo; Tomohiro WatanabeGastroenterology 2023年12月
- Hironobu Sugimori; Sho Masaki; Hajime Honjo; Masatoshi Kudo; Tomohiro WatanabeCureus 2023年11月
- Tomohiro Watanabe; Kosuke Minaga; Hajime Honjo; Masatoshi KudoBiochemical and Biophysical Research Communications 2023年06月
- Hajime Honjo; Yasuhiro Masuta; Yasuo Otsuka; Sho Masaki; Kosuke Minaga; Masatoshi Kudo; Tomohiro WatanabeDEN Open 4 1 2023年05月 [査読有り]
- Natsuki Okai; Yasuhiro Masuta; Yasuo Otsuka; Akane Hara; Sho Masaki; Ken Kamata; Kosuke Minaga; Hajime Honjo; Masatoshi Kudo; Tomohiro WatanabeJournal of Clinical Biochemistry and Nutrition 2023年
- Yasuo Otsuka; Yasuhiro Masuta; Kosuke Minaga; Natsuki Okai; Akane Hara; Ryutaro Takada; Sho Masaki; Ken Kamata; Hajime Honjo; Kouhei Yamashita; Masatoshi Kudo; Tomohiro WatanabeJournal of Clinical Biochemistry and Nutrition 2023年
- Yasuhiro Masuta; Kosuke Minaga; Yasuo Otsuka; Natsuki Okai; Akane Hara; Sho Masaki; Tomoyuki Nagai; Hajime Honjo; Masatoshi Kudo; Tomohiro WatanabeJournal of Clinical Biochemistry and Nutrition 2023年
- Hajime Honjo; Kosuke Minaga; Akane Hara; Ryutaro Takada; Yasuo Otsuka; Yasuhiro Masuta; Sho Masaki; Shigenaga Matsui; Masatoshi Kudo; Tomohiro WatanabeInternal Medicine 2023年
- IL-6応答亢進を伴う潰瘍性大腸炎関連脊椎関節炎の一例藤田 峻輔; 本庶 元; 高田 隆太郎; 原 茜; 益田 康弘; 半田 康平; 三長 孝輔; 渡邉 智裕; 工藤 正俊; 辻 成佳日本消化器病学会近畿支部例会プログラム・抄録集 118回 88 - 88 日本消化器病学会-近畿支部 2023年01月
- Yasuhiro Masuta; Yasuo Otsuka; Kosuke Minaga; Hajime Honjo; Masatoshi Kudo; Tomohiro WatanabeJournal of Clinical Biochemistry and Nutrition 2023年
- Yoriaki Komeda; Masashi Kono; Hiroshi Kashida; George Tribonias; Sho Masaki; Ryutaro Takada; Tomoyuki Nagai; Satoru Hagiwara; Naoshi Nishida; Mamoru Takenaka; Hajime Honjo; Shigenaga Matsui; Naoko Tsuji; Masatoshi KudoAnnals of gastroenterology 36 1 97 - 102 2023年BACKGROUND: The standard therapy for acute severe ulcerative colitis (ASUC) is intravenous corticosteroids; however, 30% of ulcerative colitis (UC) patients do not recover with corticosteroids alone. Few studies have reported the efficacy and safety of tofacitinib for ASUC with steroid resistance. We report a case series of successful first-line treatment consisting of tofacitinib (20 mg/day) administered to ASUC patients with steroid resistance. METHODS: Patients diagnosed with ASUC at our institution between October 2018 and February 2020 were retrospectively evaluated. They were administered a high dose of tofacitinib (20 mg) after showing no response to steroid therapy in a dose of 1-1.5 mg/kg/day. RESULTS: Eight patients with ASUC, 4 (50%) men, median age 47.1 (range 19-65) years, were included. Four patients were newly diagnosed, and the median UC duration was 4 (range 0-20) years. Six of the 8 patients were able to avoid colectomy. One patient (patient 2) had no response; however, remission was achieved after switching from tofacitinib to infliximab. One patient (patient 6) with no response to tofacitinib underwent total colectomy. Only one patient (patient 4) experienced an adverse event, local herpes zoster, treated with acyclovir without tofacitinib discontinuation. CONCLUSIONS: Clinical remission without serious adverse events can be achieved with high probability and colectomy can be avoided by first administering high-dose tofacitinib to steroid-resistant ASUC patients. Tofacitinib may be one of the first-line treatment options for steroid-resistant ASUC.
- Shunsuke Fujita; Hajime Honjo; Ryutaro Takada; Akane Hara; Yasuhiro Masuta; Yasuo Otsuka; Kohei Handa; Kosuke Minaga; Shigeyoshi Tsuji; Masatoshi Kudo; Tomohiro WatanabeInternal Medicine 2023年
- Yasuhiro Masuta; Kosuke Minaga; Masayuki Kurimoto; Ikue Sekai; Akane Hara; Naoya Omaru; Natsuki Okai; Yasuo Otsuka; Ryutaro Takada; Tomoe Yoshikawa; Sho Masaki; Ken Kamata; Hajime Honjo; Yasuyuki Arai; Kouhei Yamashita; Masatoshi Kudo; Tomohiro WatanabeInternational Immunology 2022年09月Abstract Mutations in nucleotide-binding oligomerization domain 2 (NOD2) are associated with Crohn’s disease (CD). Although NOD2 activation contributes to the maintenance of intestinal homeostasis through the negative regulation of pro-inflammatory cytokine responses mediated by Toll-like receptors (TLRs), the effects of NOD2 activation on interferon (IFN)-α responses induced by TLR9 have been poorly defined. To explore the cross-talk between NOD2 and TLR9, human monocytes or dendritic cells (DCs) were stimulated with NOD2 and/or TLR9 ligands to measure IFN-α production. The severity of dextran sodium sulfate (DSS)-induced colitis was compared in mice treated with NOD2 and/or TLR9 ligands. Expression of IFN-α and IFN-stimulated genes (ISGs) was examined in the colonic mucosa of patients with inflammatory bowel disease (IBD). NOD2 activation reduced TLR9-induced IFN-α production by monocytes and DCs in a deubiquitinating enzyme A (DUBA)-dependent manner. Activation of DUBA induced by the co-stimulation of TLR9 and NOD2 inhibited Lys63-linked polyubiquitination of TRAF3 and suppressed TLR9-mediated IFN-α production. NOD2 activation in hematopoietic cells protected mice from TLR9-induced exacerbation of DSS-induced colitis by down-regulating IFN-α responses and up-regulating DUBA expression. Colonic mucosa of patients with active and remitted IBD phases was characterized by the enhanced and reduced expression of ISGs, respectively. Expression levels of IFN-α and IL-6 positively correlated in the active colonic mucosa of patients with ulcerative colitis and CD, whereas DUBA expression inversely correlated with that of IFN-α in patients with CD. Collectively, these data suggest that DUBA-dependent negative effect of NOD2 on TLR9-mediated IFN-α responses contributes to the maintenance of intestinal homeostasis.
- Natsuki Okai; Tomohiro Watanabe; Kosuke Minaga; Ken Kamata; Hajime Honjo; Masatoshi KudoWorld journal of gastroenterology 28 26 3063 - 3070 2022年07月Crohn's disease (CD) is driven by the loss of tolerance to intestinal microbiota and excessive production of pro-inflammatory cytokines. These pro-inflammatory cytokines are produced by macrophages and dendritic cells (DCs) upon sensing the intestinal microbiota by the pattern recognition receptors (PRRs). Impaired activation of PRR-mediated signaling pathways is associated with chronic gastrointestinal inflammation, as shown by the fact that loss-of-function mutations in the nucleotide-binding oligomerization domain 2 gene increase the risk of CD development. Autophagy is an intracellular degradation process, during which cytoplasmic nutrients and intracellular pathogens are digested. Given that impaired reaction to intestinal microbiota alters signaling pathways mediated by PRRs, it is likely that dysfunction of the autophagic machinery is involved in the development of CD. Indeed, the loss-of-function mutation T300A in the autophagy related 16 like 1 (ATG16L1) protein, a critical regulator of autophagy, increases susceptibility to CD. Recent studies have provided evidence that ATG16L1 is involved not only in autophagy, but also in PRR-mediated signaling pathways. ATG16L1 negatively regulates pro-inflammatory cytokine responses of macrophages and DCs after these cells sense the intestinal microbiota by PRRs. Here, we discuss the molecular mechanisms underlying the development of CD in the T300A ATG16L1 mutation by focusing on PRR-mediated signaling pathways.
- 腸内細菌に対する炎症性サイトカイン応答の増強を示すクローン病関連脊椎関節炎の一例福西 香栄; 本庶 元; 岡井 夏輝; 河野 匡志; 鎌田 研; 三長 孝輔; 米田 頼晃; 辻 成佳; 渡邉 智裕; 工藤 正俊日本消化器病学会近畿支部例会プログラム・抄録集 116回 108 - 108 日本消化器病学会-近畿支部 2022年02月
- 腸内細菌に対する炎症性サイトカイン応答の増強を示すクローン病関連脊椎関節炎の一例福西 香栄; 本庶 元; 岡井 夏輝; 河野 匡志; 鎌田 研; 三長 孝輔; 米田 頼晃; 辻 成佳; 渡邉 智裕; 工藤 正俊日本消化器病学会近畿支部例会プログラム・抄録集 116回 108 - 108 日本消化器病学会-近畿支部 2022年02月
- 制御性T細胞に依存性しない寛解導入が得られたCollagenous Colitisの一例瀬海 郁衣; 本庶 元; 今村 瑞貴; 松原 卓哉; 河野 匡志; 原 茜; 栗本 真之; 吉川 馨介; 益田 康弘; 大塚 康生; 高田 隆太郎; 吉川 智恵; 鎌田 研; 三長 孝輔; 松井 繁長; 木村 雅友; 渡邉 智裕; 工藤 正俊日本消化器病学会近畿支部例会プログラム・抄録集 116回 117 - 117 日本消化器病学会-近畿支部 2022年02月
- Ryutaro Takada; Kosuke Minaga; Akane Hara; Yasuo Otsuka; Shunsuke Omoto; Ken Kamata; Kentaro Yamao; Mamoru Takenaka; Satoru Hagiwara; Hajime Honjo; Shigenaga Matsui; Takaaki Chikugo; Tomohiro Watanabe; Masatoshi KudoJournal of clinical medicine 10 16 2021年08月Due to the tendency of gastric linitis plastica (GLP) to cause extensive submucosal infiltration, a superficial endoscopic biopsy sometimes yields no evidence of malignancy, hindering definite diagnosis. The present study was a single-center retrospective analysis of 54 consecutive patients diagnosed with GLP between 2016 and 2020 to evaluate EUS-guided fine-needle aspiration (EUS-FNA) biopsy outcomes in patients with negative endoscopic biopsy findings. A pathological GLP diagnosis was achieved by endoscopic biopsy in 40 patients (74.1%). EUS-FNA biopsy with a 22-gauge needle was performed in 13 of the remaining 14 patients, and GLP diagnosis was confirmed in 10 patients, with a median of three needle passes. The remaining four patients were laparoscopically diagnosed with GLP. The diagnostic ability of EUS-FNA biopsy for GLP was 76.9%, and EUS-FNA biopsy contributed to GLP diagnosis in 18.5% (10/54) of all cases. None of the 13 patients exhibited EUS-FNA biopsy-related adverse events. Univariable and multivariable analyses revealed an absence of superficial ulcerations as a predictor of false-negative endoscopic biopsy findings in patients with GLP. These results suggest EUS-FNA biopsy as a minimally invasive and safe alternative diagnostic modality for GLP in cases where conventional endoscopic biopsy fails to verify malignancy, although prospective studies with larger cohorts are warranted to confirm these findings.
- Hajime Honjo; Tomohiro Watanabe; Natsuki Okai; Masashi Kono; Ken Kamata; Kosuke Minaga; Yoriaki Komeda; Shigeyoshi Tsuji; Masatoshi KudoAsian Pacific journal of allergy and immunology 2021年04月BACKGROUND: Despite the high incidence of spondyloarthritis (SpA) as an extra-intestinal manifestation of Crohn's disease (CD), the immunopathogenesis of CD-associated SpA remains largely unknown. OBJECTIVE: We tried to explore molecular mechanisms accounting for the development of CD-associated SpA in a patient successfully treated with infliximab. METHODS: Peripheral blood mononuclear cells (PBMCs) before infliximab treatment were stimulated with Toll-like receptor (TLR) ligands to measure pro-inflammatory cytokine responses. Endoscopic biopsy samples before and after infliximab treatment were subjected to quantitative polymerase chain reaction. RESULTS: PBMCs from this CD-associated SpA patient exhibited higher production of pro-inflammatory cytokines upon stimulation with TLR ligands than PBMCs from healthy controls. Induction of remission by infliximab was associated with the downregulation of pro-inflammatory cytokine responses in the small intestinal mucosa, which is continually exposed to TLR ligands. CONCLUSIONS: Excessive pro-inflammatory cytokine responses to TLR ligands might underlie the immunopathogenesis of CD-associated SpA.
- Hajime Honjo; Tomohiro Watanabe; Yasuyuki Arai; Ken Kamata; Kosuke Minaga; Yoriaki Komeda; Kouhei Yamashita; Masatoshi KudoInternational immunology 33 2 91 - 105 2021年01月Polymorphisms in the autophagy-related protein 16 like 1 (ATG16L1) and nucleotide-binding oligomerization domain 2 (NOD2) genes are associated with Crohn's disease (CD). Impaired interaction between ATG16L1 and NOD2 underlies CD immunopathogenesis. Although activation of the receptor-interacting serine-threonine kinase (RICK, also known as RIP2), a downstream signaling molecule for NOD2 and multiple toll-like receptors (TLRs), plays a pathogenic role in the development of inflammatory bowel disease, the molecular interaction between ATG16L1 and RICK/RIP2 remains poorly understood. In this study, we examined the physical interaction between ATG16L1 and RICK/RIP2 in human embryonic kidney 293 cells and human monocyte-derived dendritic cells (DCs) expressing excessive and endogenous levels of these proteins, respectively. We established that ATG16L1 binds to RICK/RIP2 kinase domain and negatively regulates TLR2-mediated nuclear factor-kappa B (NF-κB) activation and pro-inflammatory cytokine responses by inhibiting the interaction between TLR2 and RICK/RIP2. Binding of ATG16L1 to RICK/RIP2 suppressed NF-κB activation by down-regulating RICK/RIP2 polyubiquitination. Notably, the percentage of colonic DCs expressing ATG16L1 inversely correlated with IL-6 and TNF-α expression levels in the colon of CD patients. These data suggest that the interaction between ATG16L1 and RICK/RIP2 maintains intestinal homeostasis via the down-regulation of TLR-mediated pro-inflammatory cytokine responses.
- Hajime Honjo; Tomohiro Watanabe; Ken Kamata; Kosuke Minaga; Masatoshi KudoFrontiers in pharmacology 12 650403 - 650403 2021年Inflammatory bowel diseases (IBDs) are becoming more frequent worldwide. A significant fraction of patients with IBD are refractory to various types of therapeutic biologics and small molecules. Therefore, identification of novel therapeutic targets in IBD is required. Receptor-interacting serine/threonine kinase 2 (RIPK2), also known as receptor-interacting protein 2 (RIP2), is a downstream signaling molecule for nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs). RIPK2 is expressed in antigen-presenting cells, such as dendritic cells and macrophages. Recognition of microbe-associated molecular patterns by NOD1, NOD2, and TLRs leads to the interaction between RIPK2 and these innate immune receptors, followed by the release of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12/23p40 through the activation of nuclear factor kappa B and mitogen-activated protein kinases. Thus, activation of RIPK2 plays a critical role in host defense against microbial infections. Recent experimental and clinical studies have provided evidence that activation of RIPK2 is involved in the development of autoimmune diseases, especially IBDs. In addition, the colonic mucosa of patients with IBD exhibits enhanced expression of RIPK2 and associated signaling molecules. Furthermore, the blockage of RIPK2 activation ameliorates the development of experimental murine colitis. Thus, activation of RIPK2 underlies IBD immunopathogenesis. In this review, we attempt to clarify the roles played by RIPK2 in the development of IBD by focusing on its associated signaling pathways. We also discuss the possibility of using RIPK2 as a new therapeutic target in IBD.
- Hajime Honjo; Tomohiro Watanabe; Mizuki Tomooka; Takuya Matsubara; Masashi Kono; Ikue Sekai; Akane Hara; Masayuki Kurimoto; Keisuke Yoshikawa; Yasuhiro Masuta; Yasuo Otsuka; Ryutaro Takada; Tomoe Yoshikawa; Ken Kamata; Kosuke Minaga; Shigenaga Matsui; Masatomo Kimura; Masatoshi KudoFrontiers in medicine 8 678268 - 678268 2021年Collagenous colitis (CC), a prototypical microscopic colitis, is a chronic inflammatory disorder of the colon. The diagnosis of CC depends on the pathological examination. The colonic mucosa of patients with CC is characterized by the presence of a substantially thickened collagen band (>10μm) under the surface epithelium. In addition, intraepithelial and lamina propria lymphocytes are markedly increased in patients with CC. However, the roles played by the lymphocytes accumulating in the colonic mucosa of patients with CC are poorly defined. Recent studies indicate that T cells infiltrating the colonic mucosa of patients with CC are mainly represented by CD4+ T cells, CD8+ T cells, and forkhead box P3 (FOXP3)+ regulatory T cells (Tregs). Given that activation of CD4+/CD8+ T cells and FOXP3+ Tregs usually mediates pro-inflammatory and anti-inflammatory responses, respectively, alterations in the colonic numbers of these adaptive T cells might be related to the resolution of colitis in patients with CC. We determined alterations in the composition of colonic T cells by extensive immunohistochemical (IHC) analyses in a case of CC successfully treated with budesonide and metronidazole. Colonic lamina propria immune cells mainly comprised CD3+ T cells, CD4+ T cells, CD8+ T cells, CD68+ macrophages, and FOXP3+ Tregs, but not CD20+ B cells or myeloperoxidase (MPO)+ granulocytes in the active phase. During remission, the numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD68+ macrophages did not change significantly in the colonic lamina propria, whereas FOXP3+ Tregs were markedly decreased, suggesting that induction of remission was achieved in a Treg-independent manner. Thus, our study indicates that accumulation of FOXP3+ Tregs in the colonic mucosa of patients with CC might be a counter-regulatory mechanism reflecting persistent inflammation and that induction of remission might be achieved without activation of Tregs.
- Yuko Sogabe; Yuzo Kodama; Hajime Honjo; Ikuo Aoyama; Yuya Muramoto; Eri Koga; Takafumi Yanaidani; Munenori Kawai; Teppei Yoshikawa; Shimpei Matsumoto; Astushi Matsumoto; Yoshiharu Mori; Chikage Ono; Miyu Nishida; Yoshihiro Nishida; Takao Mikami; Yasuhiro Matsunaga; Yukiko Miyamoto; Motoya Kitami; Koji Nishikawa; Masahiko Kondo; Naoki Miyake; Chiharu Kawanami; Hiroshi SenoGastroenterological Endoscopy 61 1 71 - 80 2019年01月 [査読有り]
© 2019 Japan Gastroenterological Endoscopy Society. All rights reserved. Background and Aim: Cholecystitis is a major complication after self-expandable metallic stent (SEMS) placement for malignant biliary obstruction. Ischemia is one of the risk factors for cholecystitis, but little is known about the influence of tumor invasion to the feeding artery of the gallbladder on the onset of cholecystitis after SEMS placement. The aim of the present study was to identify risk factors for cholecystitis after SEMS placement. Methods: Incidence and nine predictive factors of cholecystitis were retrospectively evaluated in 107 patients who underwent SEMS placement for unresectable distal malignant biliary obstruction at Kyoto University Hospital and Otsu Red Cross Hospital between January 2012 and June 2016. Results: Cholecystitis occurred in 13 of 107 patients (12.1%) after SEMS placement during the median follow-up period of 262 days. Univariate analyses showed that tumor invasion to the feeding artery of the gallbladder and tumor involvement to the orifice of the cystic duct were significant predictors of cholecystitis (P= 0.001 and P<0.001). Multivariate analysis confirmed that these two factors were significant and independent risks for cholecystitis with odds ratios of 22.13 (95% CI, 3.57-137.18; P=0.001) and 25.26 (95% CI, 4.12-154.98; P<0.001), respectively. Conclusions: This study showed for the first time that tumor invasion to the feeding artery of the gallbladder as well as tumor involvement to the orifice of the cystic duct are independent risk factors for cholecystitis after SEMS placement. - Yuko Sogabe; Yuzo Kodama; Hajime Honjo; Ikuo Aoyama; Yuya Muramoto; Eri Koga; Takafumi Yanaidani; Munenori Kawai; Teppei Yoshikawa; Shimpei Matsumoto; Astushi Matsumoto; Yoshiharu Mori; Chikage Ono; Miyu Nishida; Yoshihiro Nishida; Takao Mikami; Yasuhiro Matsunaga; Yukiko Miyamoto; Motoya Kitami; Koji Nishikawa; Masahiko Kondo; Naoki Miyake; Chiharu Kawanami; Hiroshi SenoDigestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 30 3 380 - 387 2018年05月BACKGROUND AND AIM: Cholecystitis is a major complication after self-expandable metallic stent (SEMS) placement for malignant biliary obstruction. Ischemia is one of the risk factors for cholecystitis, but little is known about the influence of tumor invasion to the feeding artery of the gallbladder on the onset of cholecystitis after SEMS placement. The aim of the present study was to identify risk factors for cholecystitis after SEMS placement. METHODS: Incidence and nine predictive factors of cholecystitis were retrospectively evaluated in 107 patients who underwent SEMS placement for unresectable distal malignant biliary obstruction at Kyoto University Hospital and Otsu Red Cross Hospital between January 2012 and June 2016. RESULTS: Cholecystitis occurred in 13 of 107 patients (12.1%) after SEMS placement during the median follow-up period of 262 days. Univariate analyses showed that tumor invasion to the feeding artery of the gallbladder and tumor involvement to the orifice of the cystic duct were significant predictors of cholecystitis (P = 0.001 and P < 0.001). Multivariate analysis confirmed that these two factors were significant and independent risks for cholecystitis with odds ratios of 22.13 (95% CI, 3.57-137.18; P = 0.001) and 25.26 (95% CI, 4.12-154.98; P < 0.001), respectively. CONCLUSIONS: This study showed for the first time that tumor invasion to the feeding artery of the gallbladder as well as tumor involvement to the orifice of the cystic duct are independent risk factors for cholecystitis after SEMS placement.
- Yuko Sogabe; Hajime Honjo; Yuya Muramoto; Teppei Yoshikawa; Tomomi Ozawa; Shimpei Matsumoto; Takahiro Utsumi; Atsushi Matsumoto; Yoshiharu Mori; Chiharu KawanamiNihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 113 9 1588 - 93 2016年09月
- Atsushi Yamada; Takahiro Horimatsu; Yoshinaga Okugawa; Naoshi Nishida; Hajime Honjo; Hiroshi Ida; Tadayuki Kou; Toshihiro Kusaka; Yu Sasaki; Makato Yagi; Takuma Higurashi; Norio Yukawa; Yusuke Amanuma; Osamu Kikuchi; Manabu Muto; Yoshiyuki Ueno; Atsushi Nakajima; Tsutomu Chiba; C Richard Boland; Ajay GoelClinical cancer research : an official journal of the American Association for Cancer Research 21 18 4234 - 42 2015年09月PURPOSE: Circulating microRNAs (miRNA) are emerging as promising diagnostic biomarkers for colorectal cancer, but their usefulness for detecting early colorectal neoplasms remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early colorectal neoplasms. EXPERIMENTAL DESIGN: A cohort of 237 serum samples from 160 patients with early colorectal neoplasms (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyzed in a three-step approach that included a comprehensive literature review for published biomarkers, a screening phase, and a validation phase. RNA was extracted from sera, and levels of miRNAs were examined by real-time RT-PCR. RESULTS: Nine miRNAs (miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-24, miR-29a, miR-92, and miR-125b) were selected as candidate biomarkers for initial analysis. In the screening phase, serum levels of miR-21, miR-29a, and miR-125b were significantly higher in patients with early colorectal neoplasm than in healthy controls. Elevated levels of miR-21, miR-29a, and miR-125b were confirmed in the validation phase using an independent set of subjects. Area under the curve (AUC) values for serum miR-21, miR-29a, miR-125b, and their combined score in discriminating patients with early colorectal neoplasm from healthy controls were 0.706, 0.741, 0.806, and 0.827, respectively. Serum levels of miR-29a and miR-125b were significantly higher in patients who had only small colorectal neoplasms (≤5 mm) than in healthy subjects. CONCLUSIONS: Because serum levels of miR-21, miR-29a, and miR-125b discriminated patients with early colorectal neoplasm from healthy controls, our data highlight the potential clinical use of these molecular signatures for noninvasive screening of patients with colorectal neoplasia.
- Atsushi Yamada; Takahiro Horimatsu; Yoshinaga Okugawa; Naoshi Nishida; Tadayuki Kou; Toshihiro Kusaka; Hajime Honjo; Yusuke Amanuma; Osamu Kikuchi; Manabu Muto; Ajay Goel; C. Richard BolandCANCER RESEARCH 74 19 2014年10月 [査読有り]
- Shuji Hiramoto; Ayako Mizota; Akira Yoshioka; Chikage Zaima; Yuko Sogabe; Nobuhiro Hieda; Yoshihiro Nishida; Aya Mizuguchi; Nobuyuki Kakiuchi; Yasuhiro Matsunaga; Satoki Yasumura; Katsutoshi Kuriyama; Kentaro Hidaka; Wataru Tanabe; Hajime Honjo; Kazunori Hasegawa; Masahiko Kondo; Koji Nishikawa; Naoki Miyake; Chiharu Kawanami; Tomoyuki ShiraseGan to kagaku ryoho. Cancer & chemotherapy 39 8 1255 - 8 2012年08月A 41-year-old man was admitted to our hospital because of multiple liver tumors. Colonoscopy showed a mass lesion in the cecum. He was given a diagnosis of endocrine cell carcinoma by immunostaining technique, and received chemotherapy of CAPOX regimen for 3 courses. After that, he underwent second-line chemotherapy of EP(CDDP/VP-16)regimen due to deterioration of his performance status(PS), and his tumor marker NSE. He then showed dramatically improved PS, and improvement in the size of liver mets and NSE(4. 3mg/mL).
- Naoki Hiki; Michio Kaminishi; Kenjiro Yasuda; Noriya Uedo; Masumi Kobari; Terufumi Sakai; Takashi Hiratsuka; Kyota Ohno; Hajime Honjo; Sachiyo Nomura; Naohisa Yahagi; Hisao Tajiri; Hiroaki SuzukiDigestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 24 2 79 - 86 2012年03月AIM: Peppermint oil solution was found to be effective for reducing gastric spasm during upper gastrointestinal endoscopy. The aim of the present study was to assess whether the gastric peristalsis-suppressing effect is dose-dependently induced by L-menthol, the major constituent of peppermint oil, and to determine the recommended dose of an L-menthol preparation. METHODS: In this phase II, multicenter, double-blind, dose-response study, 131 eligible patients were randomly assigned to receive 20 mL of 0.4% L-menthol (n = 32), 0.8% L-menthol (n = 35), 1.6% L-menthol (n = 30), or placebo (n = 34). The primary efficacy measure was the proportion of subjects with no peristalsis in two time periods, 75 to 105 s after treatment and immediately before the completion of endoscopy. RESULTS: The peristalsis-suppressing effect of L-menthol increased dose dependently (5.6%, 32.0%, 47.4% and 52.9% in the 0%, 0.4%, 0.8% and 1.6% groups, respectively: P < 0.001, one-tailed Cochran-Armitage trend test). As compared with the placebo group, the proportion of subjects with no peristalsis after administration was significantly higher in the 0.8% group (P = 0.015) and 1.6% group (P = 0.009). Adverse events in the L-menthol dose groups occurred with similar frequencies in the placebo group. CONCLUSION: L-menthol suppresses peristalsis in a dose-dependent manner, and the dose-response reaches a plateau at 0.8% L-menthol. Further Phase III studies are needed to establish the superiority of 0.8% L-menthol over placebo.
- Naoki Hiki; Michio Kaminishi; Kenjiro Yasuda; Noriya Uedo; Hajime Honjo; Nobuyuki Matsuhashi; Takashi Hiratsuka; Chuichi Sekine; Sachiyo Nomura; Naohisa Yahagi; Hisao Tajiri; Hiroaki SuzukiGastrointestinal endoscopy 73 5 932 - 41 2011年05月BACKGROUND: GI peristalsis during GI endoscopy commonly requires intravenous or intramuscular injection of antispasmodic agents, which sometimes cause unexpected adverse reactions. OBJECTIVE: Our ultimate goal was to evaluate whether the antiperistaltic effect of L-menthol-based preparations facilitates endoscopic examinations in a clinical setting. DESIGN: Multicenter, randomized, double-blind, placebo-controlled study. SETTING: Six Japanese referral centers. PATIENTS AND INTERVENTION: A total of 87 patients scheduled to undergo upper GI endoscopy were randomly assigned to receive 160 mg of L-menthol (n=45) or placebo (n=42). Both treatments were sprayed endoscopically on the gastric mucosa. The degree of gastric peristalsis was assessed by an independent committee. MAIN OUTCOME MEASUREMENTS: The proportion of subjects with no peristalsis 90 to 135 seconds after administration and at the end of the endoscopic examination (complete suppression of gastric peristalsis). Other outcomes were the proportion of subjects with no or mild peristalsis (adequate suppression of gastric peristalsis) and the ease of intragastric observation as evaluated by the endoscopist who performed the procedure. RESULTS: Gastric peristalsis was completely suppressed in 35.6% (21.9, 51.2) of the L-menthol group compared with only 7.1% (1.5, 19.5) of the placebo group (P<.001). In the L-menthol group, 77.8% (62.9, 88.8) (35/45 subjects) of the subjects had no or mild peristalsis at the completion of endoscopy. Minor peristalsis interfered with intragastric examination in only 1 of these 35 patients (2.9%). The incidence of adverse events did not differ significantly between the groups (P=.512). LIMITATION: Small sample size. CONCLUSIONS: During upper GI endoscopy, L-menthol sprayed on the gastric mucosa significantly suppresses peristalsis with minimal adverse drug reactions compared with placebo. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00742599.).
- Rikako Koyama; Tsunao Imamura; Chikao Okuda; Natsuko Sakamoto; Hajime Honjo; Kazuo TakeuchiPancreas 37 3 259 - 64 2008年10月OBJECTIVES: Patients with autoimmune pancreatitis (AIP) commonly have lesions in the bile duct itself and show stenosis of the bile duct system; however, no detailed study has evaluated the ultrasonographic findings of bile duct lesions in AIP. In this study, we monitored the clinical course and imaging findings, mainly ultrasonographic, of bile duct lesions in AIP. METHODS: We retrospectively analyzed the incidence of bile duct lesions, imaging findings, and clinical course in 37 patients with AIP. RESULTS: Characteristic bile duct and gallbladder wall thickening was recognized on ultrasound in 37.8% (14/37) of AIP patients. We divided the patients into 2 types according to the ultrasonographic findings of bile duct wall thickening: (1) 3-layer type (64.3%) and (2) parenchymal-echo type (35.7%). All 14 cases were treated with prednisolone, with immediate resolution of the bile duct lesions. CONCLUSION: Sclerosing cholangitis is one of the extrapancreatic lesions that are commonly detected in AIP patients; it is detected on ultrasonographic imaging as characteristic wall thickening. Our ultrasonographic findings reflect the fact that bile duct wall thickening in AIP is an inflammatory process that responds to prednisolone therapy. Ultrasonography is a useful tool in detecting biliary tract lesions in AIP.
- Takatsugu Yamamoto; Yasushi Kuyama; Kazuo Takeuchi; Natsuko Nagashima; Hajime Honjo; Norio Sakurai; Chikao OkudaPancreas 26 3 313 - 4 2003年04月
- Takatsugu Yamamoto; Kiyoko Uki; Kazuo Takeuchi; Natsuko Nagashima; Hajime Honjo; Norio Sakurai; Chikao Okuda; Goro Watanabe; Masaya Mori; Yasushi KuyamaJournal of gastroenterology 38 7 704 - 6 2003年Patients troubled with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at high risk for cholangiocarcinoma, whereas cancer of the gallbladder (GBC) is rarely reported to develop in that population. A Japanese man aged 62 years with a 14-year history of PSC and UC had been found to have a protruding lesion of the gallbladder by screening sonography. The preoperative examination suggested the lesion to be GBC at an early stage. Pathology examination after cholecystectomy proved that the lesion was papillary adenocarcinoma localized in the mucosal layer. Although the prognosis of GBC is poor, the outcome of cholecystectomy against early GBC is relatively good. Early detection of the tumor is required for a better prognosis of patients with GBC. According to the review of the literature, PSC and UC patients are regarded as a high-risk group not only for cholangiocarcinoma but also GBC. It is advocated that clinicians perform repeated radiographic examinations including sonography for patients with PSC and UC even if the diseases are being controlled.
- Takatsugu Yamamoto; Kazuo Takeuchi; Natsuko Nagashima; Hajime Honjo; Norio Sakurai; Chikao Okuda; Yasushi KuyamaJournal of clinical gastroenterology 35 1 103 - 4 2002年07月
- Takatsugu Yamamoto; Kazuo Takeuchi; Natsuko Nagashima; Hajime Honjo; Norio Sakurai; Chikao Okuda; Isao Koida; Yasushi KuyamaJournal of clinical gastroenterology 34 4 491 - 2 2002年04月