Shuichi Kaneko

Kanazawa Medical University, Kanazawa, Ishikawa, Japan

Are you Shuichi Kaneko?

Claim your profile

Publications (515)2373.74 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: In the current American Joint Committee on Cancer/International Union Against Cancer staging system (seventh edition) for intrahepatic cholangiocarcinoma (ICC), tumor size was excluded, and periductal invasion was added as a new tumor classification-defining factor. The objective of the current report was to propose a new staging system for ICC that would be better for stratifying the survival of patients based on data from the nationwide Liver Cancer Study Group of Japan database. Methods: Of 756 patients who underwent surgical resection for ICC between 2000 and 2005, multivariate analyses of the clinicopathologic factors of 419 patients who had complete data sets were performed to elucidate relevant factors for inclusion in a new tumor classification and staging system. Results: Overall survival data were best stratified using a cutoff value of 2 cm using a minimal P value approach to discriminate patient survival. The 5-year survival rate of 15 patients who had ICC measuring ≤2 cm in greatest dimension without lymph node metastasis or vascular invasion was 100%, and this cohort was defined as T1. Multivariate analysis of prognostic factors for 267 patients with lymph node-negative and metastasis-negative (N0M0) disease indicated that the number of tumors, the presence arterial invasion, and the presence major biliary invasion were independent and significant prognostic factors. The proposed new system, which included tumor number, tumor size, arterial invasion, and major biliary invasion for tumor classification, provided good stratification of overall patient survival according to disease stage. Macroscopic periductal invasion was associated with major biliary invasion and an inferior prognosis. Conclusions: The proposed new staging system, which includes a tumor cutoff size of 2 cm and major biliary invasion, may be useful for assigning patients to surgery. Cancer 2015. © 2015 American Cancer Society.
    Cancer 10/2015; DOI:10.1002/cncr.29686 · 4.89 Impact Factor
  • Hepatology Research 10/2015; DOI:10.1111/hepr.12601 · 2.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Various sleep abnormalities, such as delayed sleep onset, frequent awakening and daytime sleepiness, deteriorate the quality of life in patients with chronic kidney disease (CKD), including those on haemodialysis (HD). Although there are some candidate causative molecules in the central nervous system, the contribution of peripheral blood cells (PBCs) remains unclear. In this study, we performed polysomnographic analysis in CKD patients and used PBCs to examine the expression of genes related to sleep and wakefulness states. Methods: Polysomnographic analysis was performed in 9 CKD patients and 6 controls. Genes related to sleep and wakefulness were evaluated by RNA microarray in 19 subjects, including CKD patients and control subjects. Results: Polysomnographic analysis revealed that the duration of the rapid eye movement (REM)/non-REM phases during total sleep time was different between CKD patients and healthy controls. In mRNA microarray evaluation, hierarchical clustering analysis showed different patterns of sleep-related gene expression in HD patients. mRNA expression levels of GABA receptor (GABBR2), noradrenaline receptor (ADRA1A), dopamine receptor (DRD1) and histamine receptor (HRH1) showed an inverse correlation with renal function. Moreover, the mRNA expression of orexin and its receptor (HCRTR1 and HCRTR2) was also inversely correlated with renal function. Conclusion: These data indicate that the expression of sleep-related genes in PBCs of CKD patients may be associated with sleep abnormalities.
    Clinical and Experimental Nephrology 09/2015; DOI:10.1007/s10157-015-1150-y · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Some observational studies have shown the relationships between hyperuricemia and chronic kidney disease (CKD); however, the threshold of serum uric acid (SUA) for deterioration of kidney function and the association between SUA and kidney injury by baseline kidney function remains unclear. This study aimed to clarify the relationships between SUA and reduced kidney function. Methods: We analyzed a historical cohort of male Japanese individuals who underwent medical checkup between 1998 and 2007. Participants with baseline data and who were followed up for at least one year were included and stratified according to baseline kidney function. Kidney function was classified as normal [estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m2] or mildly reduced (eGFR 60-89 ml/min/1.73 m2). The outcome measured was kidney impairment defined as a decrease in eGFR to < 60 ml/min/1.73 m2. Associations between SUA and risk for outcome and eGFR slopes were assessed. Results: A total of 41632 subjects with mean age 45.4 years were included. During a mean follow-up of four years, 3186 (7.6%) subjects developed kidney dysfunction. Subjects with SUA ≥ 6.0 mg/dL had a significantly increased risk for kidney impairment compared with subjects with SUA of 4-4.9 mg/dL. SUA threshold levels were different according to baseline kidney function; SUA ≥ 7.0 and ≥ 6.0 mg/dL for normal and mildly reduced kidney function, respectively. Approximately the same trends were observed for eGFR slopes. Conclusion: In the general population, hyperuricemia appears to be a risk factor for kidney impairment in males. For participants with mild kidney dysfunction, even a slight elevation of SUA can be a risk factor.
    PLoS ONE 09/2015; 10(9):e0137449. DOI:10.1371/journal.pone.0137449 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multidrug resistance-associated protein 3 (MRP3) is a carrier-type transport protein belonging to the ABC transporters. In this study, we investigated the safety and immunogenicity of a MRP3-derived peptide (MRP3765) as a vaccine and characterized the MRP3-specific T cell responses induced. Twelve hepatocellular carcinoma (HCC) patients treated with hepatic arterial infusion chemotherapy (HAIC) were enrolled. The MRP3-derived peptide was emulsified in incomplete Freund's adjuvant and administered via subcutaneous immunization three times weekly. No serious adverse drug reactions to the peptide vaccine were observed, and the vaccination was well tolerated. The vaccination induced MRP3-specific immunity in 72.7% of the patients. In a phenotypic analysis, the largest post-vaccinated increase in MRP3-specific T cells was due to an increase in cells with the effector memory phenotype. Among the 12 patients, one patient showed a partial response, nine showed a stable disease, and two showed a progressive disease. The median overall survival time was 14.0 months. In conclusion, the safety, effects of immune boosting, and possible prolongation of overall survival by the MRP3-derived peptide demonstrate the potential of the peptide to provide clinical benefit in HCC patients. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Cancer letters 09/2015; DOI:10.1016/j.canlet.2015.08.020 · 5.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We determined the feasibility of substituting sitagliptin or mitiglinide for bolus insulin injection therapy in patients with type 2 diabetes. 60 patients with type 2 diabetes were enrolled and randomized to switch from mealtime dosing of a rapid-acting insulin analog to either sitagliptin or mitiglinide for 16 weeks. Body weight, body mass index, and waist circumference decreased significantly in both groups at the end of the study. Mitiglinide significantly increased fasting plasma glucose (FPG) levels at the end of the study from 146.5±36.3 to 168.0±38.8 mg/dL, whereas sitagliptin did not affect FPG. Glycated hemoglobin (HbA1c) and 1,5-anhydroglucitol increased significantly in both groups. The C peptide immunoreactivity (CPR) responses after arginine were diminished in both groups. γ-GTP and triglycerides increased, and high-density lipoprotein cholesterol and adiponectin decreased, in the sitagliptin group, but not in the mitiglinide group. Mean Diabetes Treatment Satisfaction Questionnaire scores improved significantly in both groups. Patients whose mean total daily doses of rapid-acting insulin analog were 16.6 and 17.8 units were switched to sitagliptin and mitiglinide, respectively, without a change in the HbA1c level. Total insulin doses/body weight predicted changes in HbA1c only in the sitagliptin group, but not in the mitiglinide group. Use of >0.27 IU/kg of a rapid-acting insulin analog predicted an increase in HbA1c after switching to sitagliptin. The CPR index (CPI) was also a predictor for a change in HbA1c in the sitagliptin group, but not in the mitiglinide group; patients with a CPI<1.4 developed a worse HbA1c after switching to sitagliptin. Sitagliptin may predominantly act on FPG, whereas mitiglinide may act on postprandial plasma glucose to achieve glycemic control after switching from a bolus insulin regimen. Additional therapy to sitagliptin or mitiglinide is clearly required to obtain equivalent glycemic control in patients using a higher dose of insulin. (UMIN 000007051).
    08/2015; 3(1):e000122. DOI:10.1136/bmjdrc-2015-000122
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims/IntroductionTo investigate the clinical and anthropometrical parameters that are associated with non-exercise activity thermogenesis (NEAT) that is composed with basal energy expenditure (BEE) and diet-induced thermogenesis (DIT) in patients with diabetes.Materials and Methods Body composition was assessed using bioelectrical impedance, and BEE and DIT were measured using indirect calorimetry in 40 Japanese patients with diabetes.ResultsBEE correlated positively with bodyweight, BMI, fat mass, and fat-free mass and correlated negatively with age in both males and females. In multivariate logistic regression analysis, BEE correlated positively with both fat mass and fat-free mass independently of gender and age. In addition, DIT correlated positively with body weight, BMI, fat mass, and fat-free mass and correlated negatively with age in females, but not males. Fat-free mass contributed to DIT at least partly, and an aging-related decrease in DIT was observed. The best anthropometric parameter that reflected fat mass and fat-free mass was hip circumference (HC) and calf circumference (CC), respectively, in both males and females. Indeed, both HC (males, β=0.600, p<0.001; females, β=0.752, p<0.001) and CC (males, β=0.810, p=0.012; females, β=0.821, p=0.002) were correlated with BEE independently of age and gender. In addition, CC (β=0.653, p=0.009) but not HC was correlated with DIT significantly only in females, independently of age.ConclusionsHC reflects fat mass and was positively associated with BEE but not with DIT. In contrast, CC reflects fat-free mass and was positively associated with BEE in both males and females and with DIT in females.This article is protected by copyright. All rights reserved.
    08/2015; DOI:10.1111/jdi.12421
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper studies the dynamics of the hepatitis B virus (HBV) model and the therapy regimens of HBV disease. First, we propose a new mathematical model of HBV with drug resistance, and then analyze its qualitative and dynamical properties. Combining the clinical data and theoretical analysis, we demonstrate that our model is biologically plausible and also computationally viable. Second, we demonstrate that the intermittent antiviral therapy regimen is one of the possible strategies to treat this kind of complex disease. There are two main advantages of this regimen, i.e. it not only may delay the development of drug resistance, but also may reduce the duration of on-treatment time compared with the long-term continuous medication. Moreover, such an intermittent antiviral therapy can reduce the adverse side effects. Our theoretical model and computational results provide qualitative insight into the progression of HBV, and also a possible new therapy for HBV disease.
    International Journal of Bifurcation and Chaos 06/2015; 25(07):1540011. DOI:10.1142/S0218127415400118 · 1.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Differentially regulated microRNAs (miRNAs) are associated with hepatic fibrosis, but their potential usefulness for blocking hepatic fibrosis has not been fully exploited. We examined the expression of miRNAs in the liver of a transgenic mouse model in which platelet-derived growth factor C (PDGF-C) is overexpressed (Pdgf-c Tg), resulting in hepatic fibrosis and steatosis and the eventual development of hepatocellular carcinoma (HCC). Robust induction of miR-214 correlated with fibrogenesis in the liver of Pdgf-c Tg, Atherogenic high fat diet induced NASH mouse, patients with chronic hepatitis B and chronic hepatitis C. Pdgf-c Tg mice were injected with LNA-antimiR-214 via the tail vein using Invivofectamine® 2.0. and the degree of hepatic fibrosis and tumor incidence were evaluated. Pdgf-c Tg mice treated with LNA-antimiR-214 showed a marked reduction in fibrosis, and tumor incidence compared with saline- or LNA-miR-control-injected control mice. In vitro, LNA-antimiR-214 significantly ameliorated the TGF-β1-induced pro-fibrotic gene expression in Lx-2 cells. MiR-214 targets a negative regulator of EGFR signaling, Mig-6. Mimic-miR-214 decreased the expression of Mig-6 and increased the levels of EGF-mediated p-EGFR (Y1173 and Y845) and p-Met (Tyr1234/1235) in Huh-7 cells. Conversely, LNA-antimiR-214 repressed these genes expression. In conclusions, miR-214 appears to participate in the development of hepatic fibrosis by modulating EGFR and TGF-β signaling pathways. LNA-anti-miR-214 may be a potentially therapy in the prevention of hepatic fibrosis.
    Cancer Science 06/2015; DOI:10.1111/cas.12730 · 3.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocellular carcinoma is composed of a subset of cells with enhanced tumorigenicity and chemoresistance that are called cancer stem (or stem-like) cells. We explored the role of chromodomain-helicase-DNA-binding protein 4, which is encoded by the CHD4 gene and is known to epigenetically control gene regulation and DNA damage responses in EpCAM(+) liver cancer stem cells. Gene and protein expression profiles were determined by microarray and immunohistochemistry in 245 and 144 hepatocellular carcinoma patients, respectively. The relationship between gene/protein expression and prognosis was examined. The functional role of chromodomain-helicase-DNA-binding protein 4 was evaluated in primary hepatocellular carcinoma cells and in cell lines in vitro and in vivo. Chromodomain helicase DNA-binding protein 4 was abundantly expressed in EpCAM(+) hepatocellular carcinoma with expression of hepatic stem cell markers and poor prognosis in two independent cohorts. In cell lines, CHD4 knockdown increased chemosensitivity and CHD4 overexpression induced epirubicin chemoresistance. To inhibit the functions of chromodomain-helicase-DNA-binding protein 4 that are mediated through histone deacetylase and poly (ADP-ribose) polymerase, we evaluated the effect of the histone deacetylase inhibitor suberohydroxamic acid and the poly (ADP-ribose) polymerase inhibitor AG-014699. Treatment with either suberohydroxamic acid or AG-014699 reduced the number of EpCAM(+) liver cancer stem cells in vitro, and suberohydroxamic acid and AG-014699 in combination successfully inhibited tumor growth in a mouse xenograft model. Chromodomain-helicase-DNA-binding protein 4 plays a pivotal role in chemoresistance and the maintenance of stemness in liver cancer stem cells and is therefore a good target for the eradication of hepatocellular carcinoma. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 06/2015; DOI:10.1016/j.jhep.2015.06.009 · 11.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 43-year-old woman who had received anticoagulant therapy for atrial fibrillation for 2 years was admitted to our hospital with hematemesis. Endoscopy revealed a huge submucosal hematoma in the antrum of the stomach. Repeat endoscopy on day 6 showed that the submucosal hematoma had developed into a giant ulcer. Gastric mucosal biopsy and general examination confirmed a diagnosis of AL amyloidosis due to multiple myeloma. Although patients with cardiac involvement of AL amyloidosis often require anticoagulant therapy, gastrointestinal bleeding may occur. Therefore, the potential benefits of anticoagulation must be carefully weighed against the risk of hemorrhage.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 06/2015; 112(6):1023-9. DOI:10.11405/nisshoshi.112.1023
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human telomerase reverse transcriptase (hTERT) is a catalytic enzyme required for telomere elongation. In this study, we investigated the safety and immunogenicity of an hTERT-derived peptide (hTERT461) as a vaccine and characterized the hTERT-specific T cell responses induced. Fourteen hepatocellular carcinoma (HCC) patients were enrolled in the study. The hTERT-derived peptide was emulsified in incomplete Freund's adjuvant and administered via subcutaneous immunization three times biweekly. The maximum toxicity observed was grade 2 according to the common terminology criteria and mainly consisted of skin reactions at the site of vaccination. The vaccination induced hTERT-specific immunity in 71.4% patients and 57.1% patients administered hTERT461 peptide-specific T cells could prevent HCC recurrence after vaccination. In phenotypic analysis, the post-vaccinated increase in hTERT-specific T cells was due to an increase in cells with the effector memory phenotype, with the potential to produce multiple cytokines. Seven hTERT-specific T cell receptors were obtained from the vaccinated patients, showing their cytotoxic activities to hTERT-derived peptide-bearing cells. In conclusion, the safety and effects of immune boosting by hTERT461 peptide have shown the potential of the peptide to provide clinical benefits in HCC patients. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Cancer letters 05/2015; 364(2). DOI:10.1016/j.canlet.2015.04.031 · 5.62 Impact Factor
  • Shinji Kitajima · Shuichi Kaneko · Takashi Wada
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 05/2015; DOI:10.1111/1744-9987.12309 · 1.71 Impact Factor
  • Yohei Waseda · Tomoyuki Hayashi · Shuichi Kaneko
    Digestive Endoscopy 05/2015; 27(6). DOI:10.1111/den.12499 · 2.06 Impact Factor
  • Source
    International journal of cardiology 04/2015; 190(1):296-298. DOI:10.1016/j.ijcard.2015.04.196 · 4.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background New biomarkers are needed to identify the stage of hepatitis C virus (HCV)-infected diseases in order to reduce the mortality rates. Herein, we investigated whether serum 3β-hydroxysterol Δ24-reductase antibody (DHCR24 Ab) may serve as a prognostic marker for hepatitis C infection progression to hepatocellular carcinoma (HCC). Methods Serum DHCR24 Abs from 395 HCV-positive patients, including 133 chronic hepatitis (CHC), 85 liver cirrhosis (LCC), and 177 HCC (HCC-C) patients; 232 hepatitis B virus (HBV)-positive patients, including 103 chronic hepatitis (CHB), 56 liver cirrhosis (LCB), and 73 HCC (HCC-B) patients; and 24 healthy controls, were measured using enzyme-linked immunosorbent assay. Results The serum DHCR24 Ab levels were significantly higher in patients with CHC than in healthy controls, in LCC than in CHC, and in LCC than in HCC-C (P < 0.0001 for all). The concentration of serum DHCR24 Ab in HCC-B patients showed no significant difference compared to CHB and LCB patients (P = 0.1247). The DHCR24 Ab levels were significantly higher in early HCC-C than CHC or LCC patients and in late HCC-C compared to early HCC-C patients. The sensitivity of the DHCR24 Ab for HCC-C detection (70.6%) was higher than that of alpha-fetoprotein (AFP; 54.8%) and protein induced by vitamin K absence or antagonist-II (PIVKA-II; 42 · 5%). Moreover, DHCR24 was up-regulated in HCV-positive, but not HBV-positive tissues or HBV-negative, HCV-negative HCC specimens. Conclusions DHCR24 auto-antibody represents a potential noninvasive biomarker for HCV-related liver disease and may facilitate the diagnosis of PIVKA-II and AFP-negative HCC.
    04/2015; 2(6):604–612. DOI:10.1016/j.ebiom.2015.04.007
  • [Show abstract] [Hide abstract]
    ABSTRACT: An 84-year-old man was diagnosed with IgG4-related autoimmune pancreatitis and sclerosing cholangitis with jaundice. Endoscopic nasobiliary drainage was performed, but hemorrhagic shock due to multiple duodenal ulcers occurred about a week later. After several endoscopic hemostasis, he was given corticosteroids. Histopathology of duodenal ulcer biopsies showed IgG4-positive plasma cell infiltration. Reports about duodenal ulcers with IgG4-related disease are very rare and we consider this case valuable.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 04/2015; 112(4):699-706. DOI:10.11405/nisshoshi.112.699
  • [Show abstract] [Hide abstract]
    ABSTRACT: Given that pancreatic ductal adenocarcinoma (PDAC) is among the most fatal malignancies with an extremely poor prognosis, the objectives of this study were to provide a detailed understanding of PDAC pathophysiology in view of the host immune response. We examined the PDAC tissues, sera, and peripheral blood cells of PDAC patients using immunohistochemical staining, the measurement of cytokine/chemokine concentrations, gene expression analysis, and flow cytometry. PDAC tissues were infiltrated by macrophages, especially CD33+CD163+ M2 macrophages and CD4+ T cells that concomitantly express programmed cell death-1 (PD-1). Concentrations of interleukin (IL)-6, IL-7, IL-15, monocyte chemotactic protein-1, and interferon-inducible protein-1 in the sera of PDAC patients were significantly elevated. The gene expression profile of CD14+ monocytes and CD4+ T cells was discernible between PDAC patients and healthy volunteers, and the differentially expressed genes were related to activated inflammation. Intriguingly, PD-1 was significantly up-regulated in the peripheral blood CD4+ T cells of PDAC patients. Correspondingly, the frequency of CD4+PD-1+ T cells increased in the peripheral blood cells of PDAC patients, and this increase correlated to chemotherapy resistance. In conclusion, inflammatory condition in both the PDAC tissue and peripheral blood cells in PDAC patients were prominent, highlighting monocytes/macrophages as well as CD4+ T cells with influence of the clinical prognosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Cancer Science 04/2015; 106(6). DOI:10.1111/cas.12663 · 3.52 Impact Factor
  • Journal of Hepatology 04/2015; 62:S434. DOI:10.1016/S0168-8278(15)30547-X · 11.34 Impact Factor

Publication Stats

10k Citations
2,373.74 Total Impact Points


  • 1997–2015
    • Kanazawa Medical University
      • • Department of Gastroenterology
      • • Department of Internal Medicine (III)
      Kanazawa, Ishikawa, Japan
  • 1987–2015
    • Kanazawa University
      • • Department of Gastroenterology
      • • Department of Disease Control and Homeostasis
      • • Department of Internal Medicine
      • • Department of Laboratory Medicine
      • • School of Medicine
      • • Division of Immunology and Molecular Biology
      Kanazawa, Ishikawa, Japan
  • 2009
    • Jichi Medical University
      • Department of Pharmacology
      Totigi, Tochigi, Japan
  • 2002–2006
    • The University of Tokyo
      • School of Medicine
      Tōkyō, Japan
  • 1994
    • Nippon Kayaku Co., Ltd.
      Edo, Tōkyō, Japan
  • 1989
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Immunoregulation
      베서스다, Maryland, United States