Abstract:
BACKGROUND & AIMS:SIRT1 is a class III histone deacetylase that plays diverse roles in various cancers. However, the clinical significance of SIRT1 in hepatocellular carcinoma (HCC) remains unknown. METHODS:We analysed p53 mutations and the activation of SIRT1 in 252 hepatitis B virus-positive HCC cases. None of the patients had been subjected to pre-operative treatment. RESULTS:We examined 57 p53 mutations from 248 HCC tissues. Activated SIRT1 (phosphorylated form of Ser47), in the context of mutant p53, predicted a longer relapse-free survival (RFS) but not a longer overall survival (OS) (RFS: p = 0.007, OS: p = 0.280) in HCC tissues harbouring mutant p53. In multivariate analysis, activated SIRT1 remained a significant predictor of longer RFS (OR = 0.307, CI: 0.143-0.660, p=0.002). Analysis of 248 paired specimens revealed a significant correlation between activated SIRT1 (Ser47) and activated AMPK (Thr172) in HCC tissues harbouring mutant p53 (p = 0.003, n = 57). The combination of these 2 parameters was a powerful predictor for a good prognosis in these patients. In vitro, SIRT1 inactivation stimulated the growth of HCC cells, bearing mutated p53, by suppressing AMPK activity and subsequently enhancing mammalian target of rapamycin (mTOR) activity, resulting in induction of p70S6K1 activation in HCC cells. Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53-mutant cell lines with active SIRT1. CONCLUSIONS:SIRT1 exerted anti-carcinogenic effects via the AMPK-mTOR pathway in HCC in the context of mutant p53. Metformin could be a therapeutic drug for HCC in patients with mutated p53, inactivated SIRT1, and AMPK expression.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Zhang ZY,Hong D,Nam SH,Kim JM,Paik YH,Joh JW,Kwon CH,Park JB,Choi GS,Jang KY,Park CK,Kim SJdoi
10.1016/j.jhep.2014.08.007subject
Has Abstractpub_date
2015-01-01 00:00:00pages
121-30issue
1eissn
0168-8278issn
1600-0641pii
S0168-8278(14)00546-7journal_volume
62pub_type
杂志文章abstract::The heart and liver are organs that are closely related in both health and disease. Patients who undergo liver transplantation may suffer from heart disease that is: (a) related to the original cause of the liver disease such as hemochromatosis, (b) related to the liver disease itself, or (c) related to other associat...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2010.11.003
更新日期:2011-04-01 00:00:00
abstract:BACKGROUND & AIMS:Because abdominal ultrasonography cannot reliably quantify hepatic steatosis, accurate data on the incidence of non-alcoholic fatty liver disease (NAFLD) are lacking. We aimed to study the population incidence of NAFLD with state-of-the-art non-invasive tests. METHODS:This was a prospective cohort st...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.08.041
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND/AIMS:Adipocytokines play a key role in the pathophysiology of non-alcoholic fatty liver diseases (NAFLD). Whereas adiponectin has mainly anti-inflammatory functions, leptin, resistin and pre-B cell enhancing factor (PBEF)/Nampt/visfatin are considered as mainly pro-inflammatory mediators regulating metabolic...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.06.016
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND & AIMS:Individuals born between 1945 and 1965 account for nearly 75% of hepatitis C virus (HCV) infections in the United States. As this cohort ages, progressive HCV-related liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) will place a significant burden on the healthcare system. We aim ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.09.006
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND & AIMS:Myeloproliferative neoplasms (MPNs) are the most frequent cause of non-tumoural non-cirrhotic splanchnic vein thrombosis (NC-SVT). Diagnosis of MPN is based on blood cell count alterations, bone marrow histology, and detection of specific gene mutations. Next-generation sequencing (NGS) allows the sim...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.06.045
更新日期:2021-01-01 00:00:00
abstract:BACKGROUND & AIMS:Current antiviral therapies help keep HBV under control, but they are not curative, as they are unable to eliminate the intracellular viral replication intermediate termed covalently closed circular DNA (cccDNA). Therefore, there remains an urgent need to develop strategies to cure CHB. Functional sil...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.09.019
更新日期:2020-09-25 00:00:00
abstract:BACKGROUND/AIMS:Not all alcoholic patients develop severe liver disease with fibrosis progressing to cirrhosis. It is of practical importance to determine whether some markers can predict progression of liver fibrosis. METHODS:We used a baboon model that mimics human alcoholic liver disease. Cytokeratin 7 and 19 expre...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00144-2
更新日期:2003-06-01 00:00:00
abstract:BACKGROUND/AIMS:The electroencephalogram (EEG) is frequently altered in cirrhotic patients. We, therefore, performed a study to ascertain the features and the prognosis of cirrhotic patients without current overt hepatic encephalopathy (OHE) who have EEG alterations. METHODS:A series of 296 consecutive cirrhotic patie...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00129-5
更新日期:2001-07-01 00:00:00
abstract::Recently, GBV-C and HGV-two isolates of the same new flavivirus-were identified in serum samples of patients with indeterminate hepatitis and posttransfusion hepatitis, respectively. The pathogenic relevance of these viruses is still uncertain. As viral infections are presumed to trigger autoimmune processes, we inves...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80306-0
更新日期:1996-12-01 00:00:00
abstract:BACKGROUND & AIMS:Aceruloplasminemia is a rare autosomal recessive neurodegenerative disease associated with brain and liver iron accumulation which typically presents with movement disorders, retinal degeneration, and diabetes mellitus. Ceruloplasmin is a multi-copper ferroxidase that is secreted into plasma and facil...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.039
更新日期:2010-12-01 00:00:00
abstract::Hydroxyethyl starch (HES) has gained wide clinical acceptance as a colloidal plasma substitute. We were able to study the liver biopsies of two patients with renal failure who developed ascites after repeated infusions of HES. All types of liver cells displayed massive accumulation of HES with the morphologic resembla...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(86)80030-7
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND/AIMS:Although 6-thioguanine (6-TG) has been suggested as an effective treatment option for patients with inflammatory bowel disease (IBD), the recent description of its hepatotoxicity has led to the recommendation not to consider this drug. We initiated a multicenter safety study in IBD-patients treated with...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2005.02.051
更新日期:2005-08-01 00:00:00
abstract:BACKGROUND & AIMS:The pathogenesis of autoimmune hepatitis (AIH) is not understood, but it was suggested that AIH may be related to a numerical or functional impairment of CD4+CD25+FOXP3+ regulatory T cells (Treg), which are important mediators of immune tolerance to self-antigens. However, the role of Treg in AIH is n...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.02.029
更新日期:2012-07-01 00:00:00
abstract::Chronic hepatitis C is common in Saudi Arabia and most often presents in an advanced stage. To assess the response of patients to interferon, a randomized placebo-controlled double-blind study was undertaken. All but 1 patient had cirrhosis or fibrosis before interferon. After a 24-week observation period patients rec...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0168-8278(05)80552-5
更新日期:1993-11-01 00:00:00
abstract:BACKGROUND & AIMS:To evaluate the prevalence and risk factors for low bone mineral density (BMD) in persons co-infected with HIV and Hepatitis C. METHODS:HIV/HCV co-infected study participants (n=179) were recruited into a prospective cohort and underwent dual-energy X-ray absorptiometry (DXA) within 1 year of a liver...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.01.035
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND & AIMS:There is no data to suggest that the size of bile ducts, portal venules, and hepatic arterioles varies according to age in the normal human liver. We sought to examine whether hepatic arteriolar size, wall thickness, and luminal diameter change with increasing age. METHODS:Histologically normal liver...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.12.018
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatocellular ballooning is a key finding in nonalcoholic steatohepatitis (NASH). It is conventionally defined by hemotoxylin and eosin (H&E) staining showing enlarged cells with rarefied cytoplasm and recently by changes in the cytoskeleton. Fat droplets are emerging as important organelles in cell ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.031
更新日期:2010-10-01 00:00:00
abstract::Guinea pig Kupffer cells were obtained by partial digestion of the liver with pronase and collagenase and purified by centrifugal elutriation. Cells were kept in monolayer culture and their capacity to secrete superoxide anion in response to phagocytosis of zymosan was determined by the cytochrome c method. Compared t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(88)80006-0
更新日期:1988-12-01 00:00:00
abstract:BACKGROUND & AIMS:Sepsis is an acute systemic inflammatory response to infection associated with high patient mortality (28-40%). We hypothesized that interleukin (IL)-30, a novel cytokine protecting mice against liver injury resulting from inflammation, would generate a protective effect against systemic inflammation ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.12.020
更新日期:2016-05-01 00:00:00
abstract:BACKGROUND & AIMS:Resveratrol, a polyphenol found in a variety of fruits, exerts a wide range of beneficial effects on the endothelium, regulates multiple vasoactive substances and decreases oxidative stress, factors involved in the pathophysiology of portal hypertension. Our study aimed at evaluating the effects of re...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.12.012
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND/AIMS:The aim of this study was to investigate whether both matrix metalloproteinase-2 (MMP-2) and membrane type 1 MMP (MT1-MMP) participate in the spontaneous resolution of liver fibrosis. METHODS:Transcription of both genes was examined by reverse transcription-polymerase chain reaction (RT-PCR) and in sit...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00177-5
更新日期:2001-10-01 00:00:00
abstract:BACKGROUND & AIMS:Little is known about the frequency, phenotype and function of HBV-specific B cells during chronic infection. Here we study HBcAg and HBsAg-specific B cells in different clinical phases of a chronic HBV infection. METHODS:We included 118 treatment naïve and 34 nucleos(t)ide analogue-treated patients ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.01.024
更新日期:2020-07-01 00:00:00
abstract::In this Grand Round presentation, the case of a man with decompensated liver disease is described. He subsequently developed a fatal pulmonary embolism, which may not have occurred if he had been prescribed prophylactic anticoagulation to prevent venous thromboembolic disease. The burden of thrombotic disease in those...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2017.01.006
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatic stellate cells (HSCs) are known to play a role in hepatic regeneration. We investigated hepatocyte/HSC interaction and HSC activation at various times after 70% partial hepatectomy (PHx) in the rat. METHODS:The hepatic microcirculation was studied using intravital fluorescence microscopy (IVFM)...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.02.005
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND & AIMS:Sorafenib is associated with multiple adverse events (AEs), potentially causing its permanent interruption. It is unknown how physicians' experience has impacted on the management of these AEs and consequently on clinical outcomes. We aimed to assess whether AE management changed over time and if thes...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.08.015
更新日期:2019-12-01 00:00:00
abstract::Chronic cholestatic diseases, whether occurring in infancy, childhood or adulthood, are characterized by defective bile acid transport from the liver to the intestine, which is caused by primary damage to the biliary epithelium in most cases. In this article, approaches to diagnosis and management of the main specific...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(00)80421-3
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND/AIMS:Patients with hepatic encephalopathy show altered motor function, psychomotor slowing and hypokinesia. The underlying mechanisms remain unclear. This work's aims were: (1) to analyse in rats with chronic liver failure due to portacaval shunt (PCS) the neurochemical alterations in the basal ganglia-thala...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.06.019
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND & AIMS:Cerebral oxidative stress plays an important role in the pathogenesis of hepatic encephalopathy (HE), but the underlying mechanisms are incompletely understood. Herein, we analyzed a role of heme oxygenase (HO)1, iron and NADPH oxidase 4 (Nox4) for the induction of oxidative stress and senescence in H...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.06.020
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND/AIMS:In the absence of liver damage, rapid liver growth can be induced pharmacologically by so-called primary liver growth promoters. The importance of the acute-phase cytokines interleukin-6 and tumor necrosis factor-alpha for the actions of these compounds is not clear. This study aimed to investigate the ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80130-0
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND & AIMS:Therapeutic options for patients failing hepatitis C retreatment are limited. EPIC(3) included a prospective trial assessing long-term peginterferon alfa-2b (PegIFNα-2b) maintenance therapy in patients with METAVIR fibrosis scores (MFS) of F2 or F3 who previously failed hepatitis C retreatment. METHO...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jhep.2012.11.001
更新日期:2013-03-01 00:00:00