A5056616389- Hepatitis C virus research
- Liver Disease Diagnosis and Treatment
- Hepatitis B Virus Studies
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Liver Disease and Transplantation
- Hepatocellular Carcinoma Treatment and Prognosis
- Liver physiology and pathology
- Systemic Lupus Erythematosus Research
- Animal Virus Infections Studies
- Hepatitis Viruses Studies and Epidemiology
- Cell death mechanisms and regulation
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Liver Diseases and Immunity
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Endoplasmic Reticulum Stress and Disease
- Diet, Metabolism, and Disease
- Galectins and Cancer Biology
- Pancreatitis Pathology and Treatment
- Cytomegalovirus and herpesvirus research
- Cytokine Signaling Pathways and Interactions
- Platelet Disorders and Treatments
National Center for Global Health and Medicine
2015-2024
Center for Global Health
2014-2024
National Institute for Japanese Language and Linguistics
2020
Osaka University
2005-2016
Institute of Molecular Biology and Biophysics
2013
Instituto Ramón y Cajal de Investigación Sanitaria
2013
Universidad de Alcalá
2013
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2013
Hanyang University Guri Hospital
2013
Korea University
2013
Abstract Multikinase inhibitor sorafenib inhibits proliferation and angiogenesis of tumors by suppressing the Raf/MEK/ERK signaling pathway VEGF receptor tyrosine kinase. It significantly prolongs median survival patients with advanced hepatocellular carcinoma (HCC) but response is disease‐stabilizing cytostatic rather than one tumor regression. To examine mechanisms underlying relative resistance in HCC, we investigated role autophagy, an evolutionarily conserved self‐digestion pathway,...
Abstract In hepatitis C virus (HCV) infection, Th responses are implicated in the pathogenesis of liver disease. The dendritic cell (DC) is most potent activator CD4 T cells for supporting Th1 differentiation. To clarify roles DC HCV-infected individuals development responses, we generated peripheral with GM-CSF and IL-4 from 24 chronic patients 14 healthy donors. We then compared their potentials stimulating allogeneic cells, autologous against influenza A or HCV core Ags, cytokine...
Dendritic cells (DCs) augment effector functions of NK cells, but the underlying mechanisms are not fully understood. Here we show in an vitro coculture system that human monocyte-derived DCs enhance IFN-gamma production, CD69 expression, and K562 cytolytic ability when prestimulated with various maturation stimuli such as IFN-alpha or LPS. Of interest is finding cell activation mediated by LPS-stimulated was dependent on IL-12 produced DC/NK coculture, IFN-alpha-stimulated DC-mediated not....
Abstract Natural killer (NK) cells are important effector for the first line of defense against tumor, but mechanisms by which they recognize and kill human hepatocellular carcinoma (HCC) remains to be elucidated. Distant MHC class I homologs MICA MICB recently identified ligands NK cell activating receptor NKG2D. In our present study, or transcript was detected in 6 10 tissues, not surrounding non‐cancerous tissues. Immunohistochemical analysis showed that MICA/B were expressed tumor...
NK cells are potent activators of dendritic (DCs), but it remains obscure how third-party affect the ability to modulate DC functions. We show here that derived from healthy donors (N-NK), when cocultured with human liver epithelial cells, induced maturation as well activation DCs, such increased migratory capacity T cell stimulatory activity. In contrast, chronic hepatitis C virus-infected (HCV-NK) were not capable activating DCs under same conditions. comparison N-NK, HCV-NK showed higher...
Hepatitis C virus (HCV) infection induces a wide range of chronic liver injuries. The mechanism by which HCV evades the immune surveillance system remains obscure. Blood dendritic cells (DCs) consist myeloid and plasmacytoid subsets that play distinct roles in regulation antivirus responses; however, their pathogenesis are yet to be determined. We compared numbers functions DCs between 43 patients with hepatitis 26 age-matched healthy volunteers. Absolute DCs, DC progenitors periphery were...
ABSTRACT Hepatitis C virus (HCV) infection induces a wide range of chronic liver injuries; however, the mechanism through which HCV evades immune surveillance system remains obscure. Blood dendritic cells (DCs) play pivotal role in recognition viral and induction innate adaptive responses. Several reports suggest that dysfunction DCs patients with hepatitis C. Toll-like receptor (TLR) has been shown to various roles many infections; involvement proteins TLR signaling pathway not yet...
The tumor suppressor p53 has been implicated in the pathogenesis of non-cancer-related conditions such as insulin resistance, cardiac failure, and early aging. In addition, accumulation observed hepatocytes individuals with fibrotic liver diseases, but significance this is not known. Herein, we have mechanistically linked activation to fibrosis. Hepatocyte-specific deletion mice gene encoding Mdm2, a protein that promotes degradation, led hepatocyte synthesis connective tissue growth factor...
Tumor cells are characterized by uncontrolled proliferation, often driven activation of oncogenes, and apoptosis resistance. The oncogenic kinase inhibitor sorafenib can significantly prolong median survival patients with advanced hepatocellular carcinoma (HCC), although the response is disease-stabilizing cytostatic rather than one tumor regression. Bcl-xL (B cell lymphoma extra large), an antiapoptotic member B lymphoma-2 (Bcl-2) family, frequently overexpressed in HCC. Here, we present...
Abstract Angiogenesis is a critical step in the development and progression of hepatocellular carcinoma (HCC). Myeloid lineage cells, such as macrophages monocytes, have been reported to regulate angiogenesis mouse tumor models. TIE2, receptor angiopoietins, conveys pro-angiogenic signals identifies monocyte/macrophage subset with activity. Here, we analyzed occurrence kinetics TIE2-expressing monocytes/macrophages (TEMs) HCC patients. This study enrolled 168 HCV-infected patients including...
Abstract Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral disease. YKL-40, chitinase-like protein expressed in multiple tissues including liver, involved cell proliferation, inflammation and remodeling the extracellular matrix. The aim this study was to assess whether serum YKL-40 levels are associated with fibrosis NAFLD patients. Serum were quantified 111 patients 23 HCC NAFLD. To identify source immunofluorescence staining specimens from performed....
BackgroundThere is currently no anti-fibrotic drug therapy available to treat hepatitis C virus (HCV) cirrhosis. The aim of this study was assess the safety, tolerability, and effect PRI-724, a small-molecule modulator Wnt signaling, in patients with HCV cirrhosis.MethodsIn single-center, open-label, phase 1 trial, we sequentially enrolled cirrhosis who were classified as Child-Pugh (CP) class A or B. PRI-724 administered continuous intravenous infusion 10, 40, 160 mg/m2/day for six cycles...
Abstract Background To assess the recent real-world changes in etiologies of liver cirrhosis (LC) Japan, we conducted a nationwide survey annual meeting Japan Society Hepatology (JSH). Methods We investigated LC patients accumulated from 68 participants 79 institutions ( N = 48,621). next assessed changing trends by analyzing cases which year diagnosis was available 45,834). further evaluated transition real number newly identified assessing data 36 hospitals with complete datasets for...
Abstract We previously reported that monocyte-derived dendritic cells activate resting NK by expressing MHC class I-related chain A and B (MICA/B), ligands for NKG2D, in response to IFN-α, but the MICA/B expression was severely impaired patients with chronic hepatitis C virus (HCV) infection. In present study, we examined induction of on DCs various innate cytokines found from either healthy donors or HCV-infected individuals, upon IL-15 stimulation, express can cells, which is solely...
The human leukocyte antigen is a crucial genetic factor that initiates or regulates immune response by presenting foreign self antigens to T lymphocytes. aim of this study was investigate whether HLA polymorphism associated with the onset progression liver injury in chronic hepatitis C virus (HCV) infection. We determined class I and II alleles 130 (HCV)-infected patients (33 carriers persistently normal alanine transaminase [ALT] values 97 disease [CLD]). (A, B) typed serologically, (DRB1,...
Anti-apoptotic members of the Bcl-2 family, including Bcl-2, Bcl-xL, Mcl-1, Bcl-w and Bfl-1, inhibit mitochondrial pathway apoptosis. Bcl-xL Mcl-1 are constitutively expressed in liver. Although previous research established as a critical apoptosis antagonist differentiated hepatocytes, significance liver, especially conjunction with has not been clear. To examine this question, we generated hepatocyte-specific Mcl-1–deficient mice by crossing mcl-1 flox / AlbCre further crossed them bcl-x...
The polymorphisms in the interleukin (IL)-28B (interferon-lambda [IFN]-λ3) gene are strongly associated with efficacy of hepatitis C virus (HCV) clearance. Dendritic cells (DCs) sense HCV and produce IFNs, thereby playing some cooperative roles HCV-infected hepatocytes induction interferon-stimulated genes (ISGs). Blood dendritic cell antigen 3 (BDCA3)(+) DCs were discovered as a producer IFN-λ upon Toll-like receptor (TLR3) stimulation. We thus aimed to clarify BDCA3(+) anti-HCV innate...
Despite the breadth of knowledge that exists regarding function long noncoding RNAs (lncRNAs) in biological phenomena, role lncRNAs host antiviral responses is poorly understood. Here, we report lncRNA#32 associated with type I IFN signaling. The silencing dramatically reduced level IFN-stimulated gene (ISG) expression, resulting sensitivity to encephalomyocarditis virus (EMCV) infection. In contrast, ectopic expression significantly suppressed EMCV replication, suggesting positively...
We recently reported the real-world changes in etiologies of liver cirrhosis (LC) based on nationwide survey data and assessed LC with hepatocellular carcinoma (HCC).Fifty-five participants from 68 institutions provided 23,637 patients HCC-complicated LC. The changing trends were assessed. further analyzed 29 hospitals that annual number newly identified 2008 to 2016 (N = 9362) without any missing years transition real cases.In overall cohort, hepatitis C virus (HCV) infection (60.3%) B...
Abstract Background and Aims Chronic liver congestion reflecting right‐sided heart failure (RHF), Budd‐Chiari syndrome, or Fontan‐associated disease (FALD) is involved in fibrosis HCC. However, molecular mechanisms of HCC chronic remain poorly understood. Approach Results Here, we first demonstrated that promoted metastatic tumor growth using murine model by partial inferior vena cava ligation (pIVCL). As the initial step triggering promotion fibrosis, gut‐derived lipopolysaccharide (LPS)...