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Dive into the research topics where Yasunobu Abe is active.

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Featured researches published by Yasunobu Abe.


Journal of Gastroenterology | 2007

High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH

Masato Yoneda; Hironori Mawatari; Koji Fujita; Hiroshi Iida; Kyoko Yonemitsu; Shingo Kato; Hirokazu Takahashi; Hiroyuki Kirikoshi; Masahiko Inamori; Yuichi Nozaki; Yasunobu Abe; Kensuke Kubota; Satoru Saito; Tomoyuki Iwasaki; Yasuo Terauchi; Shinji Togo; Shiro Maeyama; Atsushi Nakajima

BackgroundThe changes in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However, it has remained difficult to differentiate between NASH and nonprogressive NAFLD by clinical examination. We investigated the interrelationships between serum high-sensitivity C-reactive protein (hs-CRP) and the pathogenesis and progression of NASH.MethodsHs-CRP was measured in 100 patients with histologically verified NAFLD (29 with steatosis and 71 with NASH), and a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to measure the intrahepatic mRNA expressions of CRP and interleukin (IL)-6.ResultsThe results of a multiple regression analysis revealed that in comparison with cases of steatosis, hs-CRP was significantly elevated (P = 0.0048) in cases of NASH. Furthermore, among patients with NASH, hs-CRP was significantly elevated in those with advanced fibrosis compared with that in those with mild fibrosis (P = 0.0384), even after adjustment for age, sex, presence of diabetes, body mass index, visceral fat area, subcutaneous fat area, homeostasis model assessment for insulin resistance, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol. The results of the RT-PCR analysis showed that intrahepatic mRNA expression of CRP, but not IL-6, was increased in patients with NASH compared with those with steatosis (P = 0.0228).ConclusionsThis is the first report to demonstrate consistent and profound elevation of hs-CRP in cases of NASH compared with in cases of simple nonprogressive steatosis. Our results suggest that hs-CRP may be a clinical feature that not only distinguishes NASH from simple nonprogressive steatosis but also indicates the severity of hepatic fibrosis in cases of NASH.


Cancer Prevention Research | 2010

Metformin Suppresses Colorectal Aberrant Crypt Foci in a Short-term Clinical Trial

Kunihiro Hosono; Hiroki Endo; Hirokazu Takahashi; Michiko Sugiyama; Eiji Sakai; Takashi Uchiyama; Kaori Suzuki; Hiroshi Iida; Yasunari Sakamoto; Kyoko Yoneda; Tomoko Koide; Chikako Tokoro; Yasunobu Abe; Masahiko Inamori; Hitoshi Nakagama; Atsushi Nakajima

The biguanide metformin is widely used for treating diabetes mellitus. We previously showed the chemopreventive effect of metformin in two rodent models of colorectal carcinogenesis. However, besides epidemiologic studies, little is known about the effects of metformin on human colorectal carcinogenesis. The objective of this pilot study was to evaluate the chemopreventive effect of metformin on rectal aberrant crypt foci (ACF), which are an endoscopic surrogate marker of colorectal cancer. We prospectively randomized 26 nondiabetic patients with ACF to treatment with metformin (250 mg/d, n = 12) or no treatment (control, n = 14); 23 patients were evaluable for end point analyses (9 metformin and 14 control); the two groups were similar in ACF number and other baseline clinical characteristics. Magnifying colonoscopy determined the number of rectal ACF in each patient at baseline and after 1 month in a blinded fashion (as were all laboratory end point analyses). We also examined proliferative activity in colonic epithelium (via proliferating cell nuclear antigen labeling index) and apoptotic activity (via terminal deoxynucleotidyl transferase dUTP nick-end labeling). At 1 month, the metformin group had a significant decrease in the mean number of ACF per patient (8.78 ± 6.45 before treatment versus 5.11 ± 4.99 at 1 month, P = 0.007), whereas the mean ACF number did not change significantly in the control group (7.23 ± 6.65 versus 7.56 ± 6.75, P = 0.609). The proliferating cell nuclear antigen index was significantly decreased and the apoptotic cell index remained unaltered in normal rectal epithelium in metformin patients. This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans, suggesting its promise for the chemoprevention of colorectal cancer. Cancer Prev Res; 3(9); 1077–83. ©2010 AACR.


Blood | 2015

Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma

Junichi Kiyasu; Hiroaki Miyoshi; Akie Hirata; Fumiko Arakawa; Ayako Ichikawa; Daisuke Niino; Yasuo Sugita; Yuji Yufu; Ilseung Choi; Yasunobu Abe; Naokuni Uike; Koji Nagafuji; Takashi Okamura; Koichi Akashi; Ryoichi Takayanagi; Motoaki Shiratsuchi; Koichi Ohshima

Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1(+) DLBCL. We performed PD-L1/PAX5 double immunostaining in 1253 DLBCL biopsy samples and established a new definition of PD-L1(+) DLBCL. We also defined the criteria for microenvironmental PD-L1(+) (mPD-L1(+)) DLBCL (ie, PD-L1(-) DLBCL in which PD-L1(+) nonmalignant cells are abundant in the tumor microenvironment). Of the 273 patients whose clinical information was available, quantitative analysis of PD-1(+) tumor-infiltrating lymphocytes (TILs) was performed. The prevalence rates of PD-L1(+) and mPD-L1(+) DLBCL were 11% and 15.3%, respectively. Both PD-L1(+) and mPD-L1(+) DLBCL were significantly associated with non-germinal center B-cell (GCB) type and Epstein-Barr virus positivity. The number of PD-1(+) TILs was significantly higher in GCB-type tumors and lower in mPD-L1(-) and PD-L1(+) DLBCL. Patients with PD-L1(+) DLBCL had inferior overall survival (OS) compared with that in patients with PD-L1(-) DLBCL (P = .0009). In contrast, there was no significant difference in OS between mPD-L1(+) and mPD-L1(-) DLBCL (P = .31). The expression of PD-L1 maintained prognostic value for OS in multivariate analysis (P = .0323). This is the first report describing the clinicopathological features and outcomes of PD-L1(+) DLBCL. Immunotherapy targeting the PD-1/PD-L1 pathway should be considered in this distinct DLBCL subgroup.


Cancer Science | 2009

Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era.

Ritsuko Seki; Koichi Ohshima; Tomoaki Fujisaki; Naokuni Uike; Fumio Kawano; Hisashi Gondo; Shigeyoshi Makino; Tetsuya Eto; Yukiyoshi Moriuchi; Fumihiro Taguchi; Tomohiko Kamimura; Hiroyuki Tsuda; Ryosuke Ogawa; Kazuya Shimoda; Kiyoshi Yamashita; Keiko Suzuki; Hitoshi Suzushima; Kunihiro Tsukazaki; Masakazu Higuchi; Atae Utsunomiya; Masahiro Iwahashi; Yutaka Imamura; Kazuo Tamura; Junji Suzumiya; Minoru Yoshida; Yasunobu Abe; Tadashi Matsumoto; Takashi Okamura

We evaluated the usefulness of prognostic markers in patients with diffuse large B‐cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) ± rituximab (R‐CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R‐CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl‐6), postgerminal center B cells (Multiple myeloma‐1), and apoptosis (Bcl‐2). The median follow‐up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R‐CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non‐GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 (P = 0.022) or Bcl‐6 (P = 0.021), or GCB subtype (P = 0.05) was associated with better overall survival, whereas the high expression of Bcl‐2 (P = 0.001) or MUM1 (P = 0.011), or non‐GCB subtype (P = 0.05) was associated with worse overall survival. In the R‐CHOP group, however, these biomarkers except Bcl‐6 were not significant prognostic factors. The patients with non‐GCB subtype showed improved survival in the R‐CHOP group (P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group (P < 0.001) and also in the R‐CHOP group (P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re‐evaluated. (Cancer Sci 2009; 100: 1842–1847)


Journal of Gastroenterology and Hepatology | 2003

Clinical characteristics of Japanese reflux esophagitis patients as determined by Los Angeles classification

Masahiko Inamori; Jun-Ichi Togawa; Hajime Nagase; Yasunobu Abe; Tadashi Umezawa; Atsushi Nakajima; Toshifumi Saito; Norio Ueno; Katsuaki Tanaka; Hisahiko Sekihara; Hiroki Kaifu; Hideo Tsuboi; Hideyuki Kayama; Shizuo Tominaga; Hiroshi Nagura

Background:  Recent studies have shown that the number of patients with reflux esophagitis is increasing in Japan, but the prevalence and risk factors associated with reflux esophagitis in Japanese patients are not well defined.


Journal of Viral Hepatitis | 2007

Hepatitis C virus directly associates with insulin resistance independent of the visceral fat area in nonobese and nondiabetic patients

Masato Yoneda; Satoru Saito; Toshiyuki Ikeda; K. Fujita; Hironori Mawatari; Hiroyuki Kirikoshi; Masahiko Inamori; Yuichi Nozaki; T. Akiyama; Takahashi H; Yasunobu Abe; Kensuke Kubota; Tomoyuki Iwasaki; Yasuo Terauchi; Shinji Togo; A. Nakajima

Summary.  Insulin resistance (IR) is known to be associated with the visceral adipose tissue area. Elucidation of the relationship between hepatitis C virus (HCV) and IR is of great clinical relevance, because IR promotes liver fibrosis. In this study, we tested the hypothesis that HCV infection by itself may promote IR. We prospectively evaluated 47 patients with chronic HCV infection who underwent liver biopsy. Patients with obesity, type 2 diabetes mellitus (DM), or a history of alcohol consumption were excluded. IR was estimated by calculation of the modified homeostasis model of insulin resistance (HOMA‐IR) index. Abdominal fat distribution was determined by computed tomography. Fasting blood glucose levels were within normal range in all the patients. The results of univariate analysis revealed a significant correlation between the quantity of HCV‐RNA and the HOMA‐IR (r = 0.368, P = 0.0291). While a significant correlation between the visceral adipose tissue area and the HOMA‐IR was also observed in the 97 control, nondiabetic, non‐HCV‐infected patients (r = 0.398, P < 0.0001), no such significant correlation between the visceral adipose tissue area and the HOMA‐IR (r = 0.124, P = 0.496) was observed in the patients with HCV infection. Multiple regression analysis with adjustment for age, gender and visceral adipose tissue area revealed a significant correlation between the HCV‐RNA and the HOMA‐IR (P = 0.0446). HCV is directly associated with IR in a dose‐dependent manner, independent of the visceral adipose tissue area. This is the first report to demonstrate the direct involvement of HCV and IR in patients with chronic HCV infection.


Liver International | 2009

Association between angiotensin II type 1 receptor polymorphisms and the occurrence of nonalcoholic fatty liver disease.

Masato Yoneda; Kikuko Hotta; Yuichi Nozaki; Hiroki Endo; Takashi Uchiyama; Hironori Mawatari; Hiroshi Iida; Shingo Kato; Koji Fujita; Hirokazu Takahashi; Hiroyuki Kirikoshi; Noritoshi Kobayashi; Masahiko Inamori; Yasunobu Abe; Kensuke Kubota; Satoru Saito; Shiro Maeyama; Koichiro Wada; Atsushi Nakajima

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver injury in many countries. Genetic factors are important for the development of NAFLD, as well as environmental factors. Recently an angiotensin II type 1 receptor (AGTR1) has been recognized as important in the aetiology of fibrosis in the liver.


Digestion | 2009

Incidence of Small Bowel Injury Induced by Low-Dose Aspirin: A Crossover Study Using Capsule Endoscopy in Healthy Volunteers

Hiroki Endo; Kunihiro Hosono; Masahiko Inamori; Shingo Kato; Yuichi Nozaki; Kyoko Yoneda; Tomoyuki Akiyama; Koji Fujita; Hirokazu Takahashi; Masato Yoneda; Yasunobu Abe; Hiroyuki Kirikoshi; Noritoshi Kobayashi; Kensuke Kubota; Satoru Saito; Nobuyuki Matsuhashi; Atsushi Nakajima

Background and Aims: Small intestinal toxicity of low-dose aspirin remains unclear. The purpose of this capsule endoscopy study was to assess the incidence of small bowel injury in healthy volunteers treated with short-term low-dose aspirin. Methods: Healthy subjects were randomly assigned to receive low-dose aspirin for 14 days (Aspirin group) or no drugs for 14 days (Control group). The two treatment occasions were separated by a washout period of at least 4 weeks. All subjects underwent capsule endoscopy at the end of each treatment period. Results: After 2 weeks of treatment, the percentages of subjects with small bowel pathology were 80% in the Aspirin group compared with 20% in the Control group (p = 0.023). The incidence of small bowel mucosal breaks in the Aspirin group was higher than that in the Control group, although the difference was not significant (30 vs. 0%; p = 0.210). Conclusions: This is the first pilot study using capsule endoscopy to report on the relation between small bowel injury and low-dose aspirin. Among the healthy subjects, the short-term administration of low-dose aspirin was associated with a mild mucosal inflammation of the small bowel.


Journal of Gastroenterology | 2007

Type IV collagen 7s domain is an independent clinical marker of the severity of fibrosis in patients with nonalcoholic steatohepatitis before the cirrhotic stage

Masato Yoneda; Hironori Mawatari; Koji Fujita; Kyoko Yonemitsu; Shingo Kato; Hirokazu Takahashi; Hiroyuki Kirikoshi; Masahiko Inamori; Yuichi Nozaki; Yasunobu Abe; Kensuke Kubota; Satoru Saito; Tomoyuki Iwasaki; Yasuo Terauchi; Shinji Togo; Shiro Maeyama; Atsushi Nakajima

BackgroundThe changes in nonalcoholic fatty liver disease range over a wide spectrum, extending from simple steatosis to nonalcoholic steatohepatitis (NASH). We investigated the clinical usefulness of the type IV collagen 7s domain and hyaluronic acid for predicting the severity of fibrosis before progression to the cirrhotic stage in NASH patients.MethodsThe type IV collagen 7s domain and hyaluronic acid were measured in 72 patients with histologically verified NASH.ResultsIn a univariate analysis, marked elevation of hyaluronic acid and the type IV collagen 7s domain was observed in the NASH patients with advanced fibrosis compared with those with mild fibrosis (P = 0.0028, P = 0.0006, respectively). For detection of NASH with advanced fibrosis, the area under the receiver-operating characteristic curves for type IV collagen 7s domain and hyaluronic acid were 0.767 and 0.754, respectively. However, multiple regression analysis revealed that the type IV collagen 7s domain, but not hyaluronic acid, was significantly elevated in patients with advanced fibrosis even after adjustment for age, sex, platelet count, prothrombin time, aspartate aminotransferase/alanine aminotransferase ratio, body mass index, and presence of underlying type 2 diabetes mellitus, all of which have previously been reported as useful predictors of advanced fibrosis in patients with NASH (P = 0.0127, P = 0.2804, respectively).ConclusionsThis is the first report to demonstrate a consistent and profound elevation of the type IV collagen 7s domain in NASH patients with advanced fibrosis (before progression to the stage of cirrhosis) compared with those with mild fibrosis.


Gut | 2008

Effectiveness of antiplatelet drugs against experimental non-alcoholic fatty liver disease

Koji Fujita; Yuichi Nozaki; Koichiro Wada; Masato Yoneda; Hiroki Endo; Hirokazu Takahashi; Tomoyuki Iwasaki; Masahiko Inamori; Yasunobu Abe; Noritoshi Kobayashi; Hiroyuki Kirikoshi; Kensuke Kubota; Satoru Saito; Yoji Nagashima; Atsushi Nakajima

Objective: No effective drugs have been developed to date to prevent or treat non-alcoholic fatty liver disease (NAFLD), although diet modification and exercise to improve obesity have been attempted. Therefore, development of a novel drug/strategy to treat NAFLD is urgently needed. In the present study, a novel concept is proposed for the treatment of NAFLD. Methods: Fisher 344 male rats were given a choline-deficient, l-amino acid-defined (CDAA) diet or a high-fat high-calorie (HF/HC) diet with or without the antiplatelet agents, aspirin, ticlopidine or cilostazol for 16 weeks. Liver steatosis, inflammation and fibrosis, and the possible mechanisms involved were investigated. Results: All three antiplatelet drugs, namely aspirin, ticlopidine and cilostazol, significantly attenuated liver steatosis, inflammation and fibrosis in the CDAA diet group. Of the three agents, cilostazol was the most effective, and the drug also suppressed HF/HC diet-induced liver steatosis. Cilostazol appeared to exert its beneficial effect against NAFLD by suppressing mitogen-activated protein kinase activation induced by oxidative stress and platelet-derived growth factor via intercepting signal transduction from Akt to c-Raf. Conclusion: Antiplatelet agents, especially cilostazol, offer the promise of becoming key agents for the treatment of NAFLD.

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Masato Yoneda

Yokohama City University

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Kensuke Kubota

Yokohama City University

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Hiroki Endo

Yokohama City University

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Hiroshi Iida

Yokohama City University

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