Details of a Researcher - NAKASE Hiroshi

Papers - NAKASE Hiroshi

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Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: a subanalysis of the DIAMOND trial

H. Nakase, S. Motoya, T. Matsumoto, K. Watanabe, T. Hisamatsu, N. Yoshimura, T. Ishida, S. Kato, T. Nakagawa, M. Esaki, M. Nagahori, T. Matsui, Y. Naito, T. Kanai, Y. Suzuki, M. Nojima, M. Watanabe, T. Hibi, DIAMOND study group, Akira Andoh, Toshifumi Ashida, Katsuya Endo, Yutaka Endo, Motohiro Esaki, Hiroshi Fujita, Mikihiro Fujiya, Ken Haruma, Toshifumi Hibi, Sakiko Hiraoka, Ichiro Hirata, Tadakazu Hisamatsu, Yutaka Honda, Hideki Iijima, Bunei Iizuka, Kentaro Ikeya, Takuya Inoue, Shuji Inoue, Tetsuya Ishida, Yo Ishiguro, Shunji Ishihara, Hiroaki Ito, Ryuichi Iwakiri, Takashi Kagaya, Takanori Kanai, Hiroshi Kashida, Shingo Kato, Jun Kato, Takehiko Katsurada, Fukunori Kinjyo, Kiyonori Kobayashi, Mayumi Kodama, Reiko Kunisaki, Koichi Kurahara, Takafumi Kurokami, Lee Kyouwon, Koichiro Matsuda, Kazuhiro Matsueda, Toshiyuki Matsui, Takayuki Matsumoto, Keiichi Mitsuyama, Yuji Mizokami, Satoshi Motoya, Yuji Naito, Tomoo Nakagawa, Shiro Nakamura, Hiroshi Nakase, Masanori Nojima, Masafumi Nomura, Atsuhiro Ogawa, Kazuichi Okazaki, Kazuaki Otsuka, Hirotake Sakuraba, Masayuki Saruta, Makoto Sasaki, Takayuki Shirai, Tomoaki Suga, Kazuhito Sugimura, Toshiro Sugiyama, Yasuo Suzuki, Fuminao Takeshima, Hiroyuki Tamaki, Shinji Tanaka, Satoshi Tanida, Keiichi Tominaga, Taku Tomizawa, Kenji Watanabe, Mamoru Watanabe, Shojiro Yamamoto, Masaki Yamashita, Atsushi Yoshida, Naoki Yoshimura

Alimentary Pharmacology and Therapeutics ( Blackwell Publishing Ltd ) 46 ( 9 ) 873 - 882 2017.11 [Refereed]

Background: Significance of monitoring adalimumab trough levels and anti-adalimumab antibodies (AAA) for disease outcome in Crohn's disease (CD) patients remained unclear. Aim: To evaluate the association of adalimumab trough levels and AAA at week 26 with clinical remission at week 52, the effect of azathiopurine on AAA and factors influencing trough levels in CD patients in the DIAMOND trial. Methods: We performed this study using adalimumab trough levels, AAA at week 26 and 6-thioguanine nucleotide (TGN) in red blood cells at week 12. A multiple regression model and receiver operating analysis was performed to identify factors influencing adalimumab trough levels and AAA, and adalimumab thresholds for predicting disease activity. Results: There was a significant difference of adalimumab trough level at week 26 between patients with disease remission and without at week 52 (7.7 ± 3.3 μg/mL vs 5.4 ± 4.3 μg/mL: P < .001). Adalimumab trough level of 5.0 μg/mL yielded optimal sensitivity and specificity for remission prediction (80.2% and 55.6%, respectively). AAA development at week 26 significantly affected remission at week 52 (P =.021), which was strongly associated with adalimumab trough levels. Female gender and increasing body weight were independently associated with low adalimumab trough levels, and female gender was associated with AAA development. A cut-off 6TGN level of > 222.5 p mol/8 ×108 RBCs yielded sensitivity (100%) and specificity (60.6%) for AAA negativity. Conclusion: Adalimumab trough levels and AAA occurrence were significantly associated with clinical remission. Higher 6TGN affected AAA negativity. The combination therapy is beneficial in some relevant aspects for CD patients. (UMIN Registration No. 000005146).

DOI PubMed

Downregulation of miR-186 is associated with metastatic recurrence of gastrointestinal stromal tumors.

Takeshi Niinuma, Masahiro Kai, Hiroshi Kitajima, Eiichiro Yamamoto, Taku Harada, Reo Maruyama, Takayuki Nobuoka, Toshirou Nishida, Tatsuo Kanda, Tadashi Hasegawa, Takashi Tokino, Tamotsu Sugai, Yasuhisa Shinomura, Hiroshi Nakase, Hiromu Suzuki

Oncology letters ( SPANDIDOS PUBL LTD ) 14 ( 5 ) 5703 - 5710 2017.11 [Refereed] [International journal]

Although dysregulation of microRNAs (miRNAs/miRs) is a common feature of human malignancies, its involvement in gastrointestinal stromal tumors (GISTs) is not fully understood. The present study aimed to identify the miRNAs that perform a role in GIST metastasis. miRNA expression profiles from a series of 32 primary GISTs were analyzed using microarrays, and miR-186 was observed to be downregulated in tumors exhibiting metastatic recurrence. Reverse transcription-quantitative polymerase chain reaction analysis of an independent cohort of 100 primary GISTs revealed that low miR-186 expression is associated with metastatic recurrence and a poor prognosis. Inhibition of miR-186 in GIST-T1 cells promoted cell migration. Gene expression microarray analysis demonstrated that miR-186 inhibition upregulated a set of genes implicated in cancer metastasis, including insulin-like growth factor-binding protein 3, AKT serine/threonine kinase 2, hepatocyte growth factor receptor, CXC chemokine receptor 4 and epidermal growth factor-containing fibulin-like extracellular matrix protein 1. These results suggest that the downregulation of miR-186 is involved in the metastatic recurrence of GISTs, and that miR-186 levels could potentially be a predictive biomarker for clinical outcome.

DOI PubMed

Tricho-hepato-enteric syndrome with novel SKIV2L gene mutations: A case report.

Eitaro Hiejima, Takahiro Yasumi, Hiroshi Nakase, Minoru Matsuura, Yusuke Honzawa, Hirokazu Higuchi, Ikuo Okafuji, Tohru Yorifuji, Takayuki Tanaka, Kazushi Izawa, Tomoki Kawai, Ryuta Nishikomori, Toshio Heike

Medicine ( LIPPINCOTT WILLIAMS & WILKINS ) 96 ( 46 ) e8601 2017.11 [Refereed] [International journal]

RATIONALE: Tricho-hepato-enteric syndrome (THES) is a rare disorder caused by mutations in the TTC37 or SKIV2L genes and characterized by chronic diarrhea, liver disease, hair abnormalities, and high mortality in early childhood due to severe infection or liver cirrhosis. PATIENT CONCERNS: The patient is the second child of three siblings born to non-consanguineous healthy Japanese parents. She had intrauterine growth retardation and was delivered at 33 weeks of gestation due to placental abruption. She presented with watery diarrhea, elevated levels of liver enzymes, multiple episodes of recurrent bacterial infection, and mild mental retardation. She had facial dysmorphism, including prominent forehead and hypertelorism, and had woolly hair without trichorrhexis nodosa. DIAGNOSIS: Clinical features led to consideration of THES. Novel compound heterozygous nonsense mutations, c.1420G>T (p.Q474*) and c.3262G>T (p.E1088*), in the SKIV2L gene were identified in the patient, and decreased levels of SKIV2L protein expression were revealed by flow cytometry and confirmed by western blot analysis using patient peripheral blood mononuclear cells (PBMCs). INTERVENTIONS: Total parenteral nutrition was required from day 30 to day 100. Trimethoprim-sulfamethoxazole prophylaxis was started at the age of 7 years after multiple episodes of bacterial pneumonia and otitis media. OUTCOMES: Chronic diarrhea persisted for more than 10 years, but the symptoms gradually improved with age. At the age of 13 years, she started a normal diet in combination with oral nutritional supplementation and her height and weight were just below the 3rd percentile for healthy individuals. She developed secondary sex characteristics, and menarche occurred at the age of 12 years. Facial dysmorphism, including prominent forehead and hypertelorism, and woolly hair without trichorrhexis nodosa became noticeable as she matured. LESSONS: Physicians must be aware of THES when they encounter a patient with infantile diarrhea, hair abnormalities, immune deficiency, mental retardation, and liver disease. Moreover, flow cytometric detection of SKIV2L protein in PBMCs may facilitate early diagnosis.

DOI PubMed

Cutting Edge: A Critical Role of Lesional T Follicular Helper Cells in the Pathogenesis of IgG4-Related Disease.

Ryuta Kamekura, Kenichi Takano, Motohisa Yamamoto, Koji Kawata, Katsunori Shigehara, Sumito Jitsukawa, Tomonori Nagaya, Fumie Ito, Akinori Sato, Noriko Ogasawara, Chieko Tsubomatsu, Hiroki Takahashi, Hiroshi Nakase, Tetsuo Himi, Shingo Ichimiya

Journal of immunology (Baltimore, Md. : 1950) ( AMER ASSOC IMMUNOLOGISTS ) 199 ( 8 ) 2624 - 2629 2017.10 [Refereed] [International journal]

IgG4-related disease (IgG4-RD) is a newly recognized systemic chronic fibroinflammatory disease. However, the pathogenesis of IgG4-RD remains unknown. To determine the pathophysiologic features of IgG4-RD, we examined T follicular helper (Tfh) cells in lesions and blood from patients with IgG4-RD. Patients with IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) showed increased infiltration of Tfh cells highly expressing programmed death 1 and ICOS in submandibular glands. Tfh cells from IgG4-DS submandibular glands had higher expression of B cell lymphoma 6 and a greater capacity to help B cells produce IgG4 than did tonsillar Tfh cells. We also found that the percentage of programmed death 1hi circulating Tfh cells in IgG4-DS patients was higher than that in healthy volunteers and was well correlated with clinical parameters. Our findings indicate that anomalous Tfh cells in tissue lesions of IgG4-RD have features distinct from those in lymphoid counterparts or blood and potentially regulate local IgG4 production in IgG4-RD.

DOI PubMed

Author's Reply.

Tomoya Iida, Hiroyuki Kaneto, Hiroshi Nakase

Intestinal research 15 ( 4 ) 554 - 554 2017.10 [Refereed] [International journal]

DOI PubMed

ヒストンメチル化酵素DOT1Lは多発性骨髄腫の治療標的となりうる

石黒一也, 佐々木基, 若杉英樹, 北嶋洋志, 新沼猛, 丸山玲緒, 甲斐正広, 池田博, 石田禎夫, 佐々木泰史, 時野隆至, 仲瀬裕志, 鈴木拓

日本癌学会総会記事 ( (一社)日本癌学会 ) 76回 P - 2244 2017.09

口腔扁平上皮癌の全エクソン解析

佐々木泰史, 田村みゆき, 中垣貴文, 小山良太, 井戸川雅史, 荻和弘, 平塚博義, 仲瀬裕志, 時野隆至

日本癌学会総会記事 ( (一社)日本癌学会 ) 76回 P - 3044 2017.09

Endoscopic removal of an impacted barolith at the sigmoid colon: a rare case report.

Tomoya Iida, Takehiro Hirano, Kei Onodera, Toshiyuki Kubo, Kentaro Yamashita, Hiroo Yamano, Hiroshi Nakase

Clinical journal of gastroenterology 10 ( 4 ) 361 - 363 2017.08 [Refereed] [Domestic journal]

A 45-year-old woman visited our hospital complaining of abdominal pain 1 week after undergoing an annual medical checkup. Her vital signs and blood test results were normal, but tenderness was found in the lower abdomen. A high-density round structure found at the midline of the lower abdomen on an abdominal radiograph was thought to be an accumulation of barium (a barolith) from upper gastrointestinal barium radiography. Two liters of an oral gastrointestinal cleaning agent was administered, but defecation did not occur. Lower gastrointestinal endoscopy revealed that the barolith was impacted at the sigmoid colon. We unsuccessfully attempted to move it using a pressurized water jet and forceps, but it was too large to be captured by the net. Therefore, we broke it down using a snare. After a successful endoscopic procedure, 120 mL of a glycerin enema solution was injected through the forceps opening, causing the barolith to be excreted. There is only one similar case of successful endoscopic treatment of a barolith in the literature.

DOI PubMed

Epigenetic silencing of diacylglycerol kinase gamma in colorectal cancer.

Masahiro Kai, Eiichiro Yamamoto, Akiko Sato, Hiro-O Yamano, Takeshi Niinuma, Hiroshi Kitajima, Taku Harada, Hironori Aoki, Reo Maruyama, Mutsumi Toyota, Tomo Hatahira, Hiroshi Nakase, Tamotsu Sugai, Toshiharu Yamashita, Minoru Toyota, Hiromu Suzuki

Molecular carcinogenesis ( WILEY ) 56 ( 7 ) 1743 - 1752 2017.07 [Refereed] [International journal]

Diacylglycerol kinases (DGKs) are important regulators of cell signaling and have been implicated in human malignancies. Whether epigenetic alterations are involved in the dysregulation of DGKs in cancer is unknown, however. We therefore analyzed methylation of the promoter CpG islands of DGK genes in colorectal cancer (CRC) cell lines. We found that DGKG, which encodes DGKγ, was hypermethylated in all CRC cell lines tested (n = 9), but was not methylated in normal colonic tissue. Correspondingly, DGKG expression was suppressed in CRC cell lines but not in normal colonic tissue, and was restored in CRC cells by treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC). DGKG methylation was frequently observed in primary CRCs (73/141, 51.8%) and was positively associated with KRAS and BRAF mutations and with the CpG island methylator phenotype (CIMP). DGKG methylation was also frequently detected in colorectal adenomas (89 of 177, 50.3%), which suggests it is an early event during colorectal tumorigenesis. Ectopic expression of wild-type DGKγ did not suppress CRC cell proliferation, but did suppress cell migration and invasion. Notably, both constitutively active and kinase-dead DGKγ mutants exerted inhibitory effects on CRC cell proliferation, migration and invasion, and the wild-type and mutant forms of DGKγ all suppressed Rac1 activity in CRC cells. These data suggest DGKG may play a tumor suppressor role in CRC.

DOI PubMed

Long non-coding RNA NEAT1 is a transcriptional target of p53 and modulates p53-induced transactivation and tumor-suppressor function.

Masashi Idogawa, Tomoko Ohashi, Yasushi Sasaki, Hiroshi Nakase, Takashi Tokino

International journal of cancer 140 ( 12 ) 2785 - 2791 2017.06 [Refereed] [International journal]

p53 is one of the most important tumor suppressor genes, and the direct transcriptional targets of p53 must be explored to elucidate its functional mechanisms. Thus far, the p53 targets that have been primarily studied are protein-coding genes. Our previous study revealed that several long non-coding RNAs (lncRNAs) are direct transcriptional targets of p53, and knockdown of specific lncRNAs modulates p53-induced apoptosis. In this study, analysis of next-generation chromatin immunoprecipitation-sequencing (ChIP-seq) data for p53 revealed that the lncRNA NEAT1 is a direct transcriptional target of p53. The suppression of NEAT1 induction by p53 attenuates the inhibitory effect of p53 on cancer cell growth and also modulates gene transactivation, including that of many lncRNAs. Furthermore, low expression of NEAT1 is related to poor prognosis in several cancers. These results indicate that the induction of NEAT1 expression contributes to the tumor-suppressor function of p53 and suggest that p53 and NEAT1 constitute a transcriptional network contributing to various biological functions and tumor suppression.

DOI PubMed

Insulin-like growth factor-1, IGF binding protein-3, and the risk of esophageal cancer in a nested case-control study.

Yasushi Adachi, Masanori Nojima, Mitsuru Mori, Kentaro Yamashita, Hiro-O Yamano, Hiroshi Nakase, Takao Endo, Kenji Wakai, Kiyomi Sakata, Akiko Tamakoshi

World journal of gastroenterology 23 ( 19 ) 3488 - 3495 2017.05 [Refereed] [International journal]

AIM: To assess the relationship between serum levels of insulin-like growth factor-1 (IGF1)/IGF-binding protein-3 (IGFBP3) and the risk of esophageal carcinoma. METHODS: We assessed the relationship between the serum levels of these molecules and the risk of esophageal cancer in a prospective, nested case-control study of participants from the Japan Collaborative Cohort Study. A baseline survey was conducted from 1988 to 1990. Of the 110585 enrolled participants, 35% donated blood samples. Those who had been diagnosed with esophageal cancer were considered cases for nested case-control studies. A conditional logistic model was used to estimate odds ratios for the incidence of esophageal cancer associated with serum IGF1 and IGFBP3 levels. RESULTS: Thirty-one cases and 86 controls were eligible for the present assessment. The molar ratio of IGF1/IGFBP3, which represents the free and active form of IGF1, was not correlated with the risk of esophageal carcinoma. A higher molar difference between IGFBP3 and IGF1, which estimates the free form of IGFBP3, was associated with a decreased risk of esophageal carcinoma (P = 0.0146), and people in the highest tertile had the lowest risk (OR = 0.107, 95%CI: 0.017-0.669). After adjustment for body mass index, tobacco use, and alcohol intake, the molar difference of IGFBP3-IGF1 was inversely correlated with the risk of esophageal carcinoma (P = 0.0150). CONCLUSION: The free form of IGFBP3, which is estimated by this molar difference, may be inversely associated with esophageal cancer incidence.

DOI PubMed

自己免疫性膵炎に対する診療の現状と長期予後当科における自己免疫性膵炎を含むIgG4関連疾患の検討

本谷雅代, 山本元久, 志谷真啓, 佐々木基, 阿久津典之, 佐々木茂, 高橋裕樹, 仲瀬裕志

膵臓 ( (一社)日本膵臓学会 ) 32 ( 3 ) 356 - 356 2017.05

Osteopontin attenuates acute gastrointestinal graft-versus-host disease by preventing apoptosis of intestinal epithelial cells.

Kentaro Kawakami, Naoki Minami, Minoru Matsuura, Tomoya Iida, Takahiko Toyonaga, Kanna Nagaishi, Yoshiaki Arimura, Mineko Fujimiya, Toshimitsu Uede, Hiroshi Nakase

Biochemical and biophysical research communications ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 485 ( 2 ) 468 - 475 2017.04 [Refereed] [International journal]

BACKGROUND AND AIMS: Acute graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation, which often targets gastrointestinal (GI) tract. Osteopontin (OPN) plays an important physiological role in the efficient development of Th1 immune responses and cell survival by inhibiting apoptosis. The role of OPN in acute GI-GVHD is poorly understood. In the present study, we investigated the role of OPN in donor T cells in the pathogenicity of acute GI-GVHD. METHODS: OPN knockout (KO) mice and C57BL/6 (B6) mice were used as donors, and (C57BL/6 × DBA/2) F1 (BDF1) mice were used as allograft recipients. Mice with acute GI-GVHD were divided into three groups: the control group (BDF1→BDF1), B6 group (B6→BDF1), and OPN-KO group (OPN-KO→BDF1). Bone marrow cells and spleen cells from donors were transplanted to lethally irradiated recipients. Clinical GVHD scores were assessed daily. Recipients were euthanized on day 7 after transplantation, and colons and small intestines were collected for various analyses. RESULTS: The clinical GVHD score in the OPN-KO group was significantly increased compared with the B6 and control groups. We observed a difference in the severity of colonic GVHD between the OPN-KO group and B6 group, but not small intestinal-GVHD between these groups. Interferon-γ, Tumor necrosis factor-α, Interleukin-17A, and Interleukin-18 gene expression in the OPN-KO group was differed between the colon and small intestine. Flow cytometric analysis revealed that the fluorescence intensity of splenic and colonic CD8 T cells expressing Fas Ligand was increased in the OPN-KO group compared with the B6 group. CONCLUSION: We demonstrated that the importance of OPN in T cells in the onset of acute GI-GVHD involves regulating apoptosis of the intestinal cell via the Fas-Fas Ligand pathway.

DOI PubMed

MicroRNA-196b is an independent prognostic biomarker in patients with pancreatic cancer.

Shinichi Kanno, Katsuhiko Nosho, Keisuke Ishigami, Itaru Yamamoto, Hideyuki Koide, Hiroyoshi Kurihara, Kei Mitsuhashi, Masahiro Shitani, Masayo Motoya, Shigeru Sasaki, Tokuma Tanuma, Hiroyuki Maguchi, Tadashi Hasegawa, Yasutoshi Kimura, Ichiro Takemasa, Yasuhisa Shinomura, Hiroshi Nakase

Carcinogenesis ( OXFORD UNIV PRESS ) 38 ( 4 ) 425 - 431 2017.04 [Refereed] [International journal]

Pancreatic cancer is a highly aggressive malignancy, with <50% patients surviving beyond 6 months after the diagnosis, and thus, there is an urgent need to explore new diagnostic and therapeutic approaches for this disease. Therefore, we conducted microRNA (miRNA) array analysis to detect miRNA molecules potentially associated with pancreatic cancer malignancy. To assess the identified miRNAs, we performed quantitative reverse transcription-PCR on 248 pancreatic ductal adenocarcinomas (UICC stage II). We also examined miRNA expression [microRNA-21 (miR-21) and microRNA-31 (miR-31)] and epigenetic alterations, including CpG island methylator phenotype (CIMP), potentially associated with the identified miRNAs. For functional analysis, we conducted proliferation and invasion assays using a pancreatic cancer cell line. miRNA array analysis revealed that microRNA-196b (miR-196b) was the most up-regulated miRNA in pancreatic cancer tissues compared with normal pancreatic duct cells. High miR-196b expression was associated with miR-21 (P = 0.0025) and miR-31 (P = 0.0001) expression. It was also related to poor prognosis in the multivariate analysis using overall survival (hazard ratio: 1.66; 95% confidence interval: 1.09-2.54; P = 0.019). Functional analysis demonstrated that miR-196b inhibitor decreased cell proliferation and that miR-196b mimic promoted cancer cell invasion. In conclusion, a significant association of high miR-196b expression with poor prognosis was observed in pancreatic cancer. Our data also revealed that miR-196b played an oncogenic role and that the transfection of the miR-196b inhibitor had an anti-tumour effect in the pancreatic cancer cell line. These results suggest that miR-196b is a promising diagnostic biomarker and therapeutic target in pancreatic cancer.

DOI PubMed

Clinical outcomes of sigmoid colon volvulus: identification of the factors associated with successful endoscopic detorsion.

Tomoya Iida, Suguru Nakagaki, Shuji Satoh, Haruo Shimizu, Hiroyuki Kaneto, Hiroshi Nakase

Intestinal research 15 ( 2 ) 215 - 220 2017.04 [Refereed] [International journal]

BACKGROUND/AIMS: Although multiple treatment options exist for the management of sigmoid colon volvulus, no study has examined the factors associated with successful endoscopic detorsion. This study aimed to examine the clinical course of patients with sigmoid colon volvulus and to identify factors related to successful endoscopic detorsion. METHODS: This study included 30 cases (21 patients) of sigmoid volvulus from among 545 cases of intestinal obstruction at a single center. We retrospectively examined the clinical course and the factors associated with the possibility of endoscopic detorsion of sigmoid colon volvulus. RESULTS: The rate of laxative use among the study participants was 76.2%; the rate of comorbid neuropsychiatric disorders was 61.9%; and 57.1% of patients had a history of open abdominal surgery. All patients were initially treated with endoscopic detorsion, and this procedure had a 61.9% success rate. The recurrence rate after detorsion was as high as 46.2%, but detorsion during revision endoscopy was possible in all cases. Statistical analysis revealed that the absence of abdominal tenderness (P=0.027), the use of laxatives (P=0.027), and a history of open abdominal surgery (P=0.032) were factors predictive of successful endoscopic detorsion. CONCLUSIONS: The results of our study are consistent with previous reports with respect to the success rate of endoscopic detorsion, the subsequent recurrence rate, and the proportion of patients requiring surgical treatment. In addition, we identified the absence of abdominal tenderness, the use of laxatives, and history of open abdominal surgery as factors predicting successful endoscopic detorsion of sigmoid colon volvulus.

DOI PubMed

膵癌と腫瘤形成性膵炎の鑑別にContrast-enhanced harmonic EUS(CH-EUS)は有用か

三宅高和, 志谷真啓, 大和田紗恵, 大久保陽介, 平野雄大, 佐々木基, 若杉英樹, 阿久津典之, 本谷雅代, 佐々木茂, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 59 ( Suppl.1 ) 1038 - 1038 2017.04

EZH2 expression is a prognostic biomarker in patients with colorectal cancer treated with anti-EGFR therapeutics.

Itaru Yamamoto, Katsuhiko Nosho, Shinichi Kanno, Hisayoshi Igarashi, Hiroyoshi Kurihara, Keisuke Ishigami, Kazuya Ishiguro, Kei Mitsuhashi, Reo Maruyama, Hideyuki Koide, Hiroyuki Okuda, Tadashi Hasegawa, Yasutaka Sukawa, Kenji Okita, Ichiro Takemasa, Hiroyuki Yamamoto, Yasuhisa Shinomura, Hiroshi Nakase

Oncotarget 8 ( 11 ) 17810 - 17818 2017.03 [Refereed] [International journal]

The polycomb group protein enhancer of zeste homolog 2 (EZH2) is a methyltransferase that suppresses microRNA-31 (miR-31) in various human malignancies including colorectal cancer. We recently suggested that miR-31 regulates the signaling pathway downstream of epidermal growth factor receptor (EGFR) in colorectal cancer. Therefore, we conducted this study for assessing the relationship between EZH2 expression and clinical outcomes in patients with colorectal cancer treated with anti-EGFR therapeutics. We immunohistochemically evaluated EZH2 expression and assessed miR-31 and gene mutations [KRAS (codon 61/146), NRAS (codon 12/13/61), and BRAF (codon 600)] in 109 patients with colorectal cancer harboring KRAS (codon 12/13) wild-type. We also evaluated the progression-free survival (PFS) and overall survival (OS). In the result, low EZH2 expression was significantly associated with shorter PFS (log-rank test: P = 0.023) and OS (P = 0.036) in patients with colorectal cancer. In the low-miR-31-expression group and the KRAS (codon 61/146), NRAS, and BRAF wild-type groups, a significantly shorter PFS (P = 0.022, P = 0.039, P = 0.021, and P = 0.036, respectively) was observed in the EZH2 low-expression groups than in the high-expression groups. In the multivariate analysis, low EZH2 expression was associated with a shorter PFS (P = 0.046), independent of the mutational status and miR-31. In conclusion, EZH2 expression was associated with survival in patients with colorectal cancer who were treated with anti-EGFR therapeutics. Moreover, low EZH2 expression was independently associated with shorter PFS in patients with cancer, suggesting that EZH2 expression is a useful additional prognostic biomarker for anti-EGFR therapy.

DOI PubMed

5-Aminosalicylic acid.

Tomoya Iida, Kei Onodera, Hiroshi Nakase

Nihon rinsho. Japanese journal of clinical medicine 75 ( 3 ) 392 - 397 2017.03 [Refereed] [Domestic journal]

Despite the emergence of new biological therapies that aim for mucosal healing as a new therapeutic target, the importance of 5-ASA formulations in the standard treatment for inflammatory bowel diseases, particularly ulcerative colitis, remains unchanged. With a growing number of patients suffering from inflammatory bowel diseases in Japan, general physicians are also increasingly prescribing 5-ASA formulations. In order to obtain the maximum efficacy of 5-ASA formulations when treating inflammatory bowel diseases, it is essential that the dosage and administration are appropriate.

PubMed

当科におけるC型慢性肝疾患に対するDAAsの現状

平野雄大, 阿久津典之, 若杉英樹, 高木秀安, 安達雄哉, 大和田紗恵, 大久保陽介, 三宅高和, 飯田智哉, 佐々木基, 志谷真啓, 本谷雅代, 佐々木茂, 仲瀬裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 ) 114 ( 臨増総会 ) A364 - A364 2017.03

Role of Small GTPase Ral in the Mechanism of Colitis-associated Cancer

Tomoya Iida, Naoki Minami, Kentaro Kawakami, Hiroki Ikeuchi, Seiichi Hirotak, Ryutaro Shirakawa, Hisanori Horiuchi, Hiroshi Nakase

INFLAMMATORY BOWEL DISEASES ( LIPPINCOTT WILLIAMS & WILKINS ) 23 S81 - S82 2017.02 [Refereed]

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Papers - NAKASE Hiroshi