Abstract:
BACKGROUND & AIMS:Recently, we have shown that micro-metastases, in the hypoxic transition zone surrounding lesions generated by radiofrequency ablation (RFA), display strongly accelerated outgrowth. CD95 is best known for its ability to induce apoptosis but can also promote tumorigenesis in apoptosis-resistant tumor cells. Therefore, we tested whether CD95 signaling plays a role in accelerated outgrowth of colorectal liver metastases following RFA. METHODS:Hypoxia-induced invasion was assessed in three-dimensional EGFP-expressing C26 tumor cell cultures by confocal microscopy. CD95 localization was tested by immunofluorescence. Invasion and outgrowth of liver metastases following RFA were analyzed by post-mortem confocal microscopy and by morphometric assessment of tumor load. Neutralization of CD95L was performed by using antibody MFL4. CD95 was suppressed by lentiviral RNA interference. The role of host CD95L was assessed using gld mice. RESULTS:Micro-metastases in the hypoxic transition zone following RFA displayed a highly invasive phenotype and increased expression of CD95 and CD95L. Hypoxia-induced tumor cell invasion in vitro increased the expression of CD95 and CD95L and induced translocation of CD95 to the invasive front. In vitro invasion, metastasis invasion, and accelerated tumor growth in the transition zone were strongly suppressed by neutralizing CD95L or by suppressing tumor cell CD95. In contrast, metastasis invasion and outgrowth were unaffected in gld mice. CONCLUSIONS:Hypoxia causes autocrine activation of CD95 on colorectal tumor cells, thereby promoting local invasion and accelerated metastasis outgrowth in the hypoxic transition zone following RFA. Further pre-clinical work is needed to assess the role of CD95L neutralization, either alone or in combination with chemotherapy, in limiting aggressive recurrence of liver metastases following RFA.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Nijkamp MW,Hoogwater FJ,Steller EJ,Westendorp BF,van der Meulen TA,Leenders MW,Borel Rinkes IH,Kranenburg Odoi
10.1016/j.jhep.2010.04.040subject
Has Abstractpub_date
2010-12-01 00:00:00pages
1069-77issue
6eissn
0168-8278issn
1600-0641pii
S0168-8278(10)00689-6journal_volume
53pub_type
杂志文章abstract:BACKGROUND/AIMS:Severe alcoholic hepatitis occurs mainly in patients with cirrhosis, and has a high death rate. Corticosteroid therapy has been particularly advocated as reducing mortality in patients with severe histologic lesions. However, identification of these patients is difficult, requiring transvenous liver bio...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80391-8
更新日期:2000-03-01 00:00:00
abstract:BACKGROUND/AIMS:The administration of a methionine and choline deficient (MCD) diet to mice serves as an animal model of NASH. The multidrug resistant 2 (Mdr2) P-glycoprotein encodes for the canalicular phospholipid transporter, and Mdr2 (+/-) mice secrete 40% less phosphatidylcholine than wild-type mice. We have hypot...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.08.026
更新日期:2006-03-01 00:00:00
abstract::Reactivation of Hedgehog (Hh), a morphogenic signaling pathway that controls progenitor cell fate and tissue construction during embryogenesis occurs during many types of liver injury in adult. The net effects of activating the Hedgehog pathway include expansion of liver progenitor populations to promote liver regener...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2010.10.003
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND & AIMS:Recently, the PAGE-B score and Toronto HCC risk index (THRI) have been developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB). We aimed to validate PAGE-B scores and THRI in Asian patients with CHB and suggested modified PAGE-B scores to im...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.07.018
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND/AIMS:A recently identified DNA virus, termed TT virus (TTV), has been associated with post-transfusional hepatitis, and a high prevalence of TTV infection in patients with acute or chronic liver disease of unknown etiology has been reported from Japan, but few data are available about TTV infection in other ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80256-6
更新日期:1999-06-01 00:00:00
abstract::It has been suggested that the cellular immune response to HBV antigens is responsible for hepatocellular injury in acute and chronic hepatitis B. However, definitive immunological studies have so far been hampered by the lack of appropriate model systems to study HBV antigen-specific T cells. The availability of high...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(88)80503-8
更新日期:1988-08-01 00:00:00
abstract:BACKGROUND/AIMS:The endogenous low molecular weight iron chelator, citrate, is considered to be an important contributor to iron transport and the liver the main site of uptake of iron citrate in subjects suffering from diseases of iron overload. Moreover, the citrate-metabolising enzyme, aconitase, is implicated in th...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80156-6
更新日期:1998-10-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatic stellate cells (HSCs) have a role in liver fibrosis. Guanine nucleotide-binding α-subunit 12 (Gα12) converges signals from G-protein-coupled receptors whose ligand levels are elevated in the environment during liver fibrosis; however, information is lacking on the effect of Gα12 on HSC trans-d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.10.011
更新日期:2018-03-01 00:00:00
abstract:BACKGROUND & AIMS:Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of In...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.04.027
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND AND AIMS:Primary sclerosing cholangitis (PSC) is an idiopathic, chronic cholestatic liver disorder characterized by biliary inflammation and fibrosis. Increased numbers of intrahepatic interferon-γ- (IFNγ) producing lymphocytes have been documented in patients with PSC, yet their functional role remains to b...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.05.023
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND & AIMS:Tumor shrinkage has been considered a fundamental surrogate efficacy measure for new cancer treatments. However, in patients treated with sorafenib for advanced hepatocellular carcinoma (HCC), tumor shrinkage rarely accompanies increased survival, thereby questioning the prognostic value of imaging-ba...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.02.016
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND & AIMS:Primary non-function and ischaemic cholangiopathy are the most feared complications following donation-after-circulatory-death (DCD) liver transplantation. The aim of this study was to design a new score on risk assessment in liver-transplantation DCD based on donor-and-recipient parameters. METHODS:...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.10.034
更新日期:2018-03-01 00:00:00
abstract:AIM/METHODS:To elucidate the metabolic effect of interferon alpha, the following tests were performed on 14 patients with chronic active hepatitis C before and after interferon therapy (6 million units/day for 2 weeks): (1) oral glucose tolerance tests to measure insulin secretion; (2) euglycemic hyperinsulinemic clamp...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/0168-8278(88)80004-7
更新日期:1998-02-01 00:00:00
abstract:BACKGROUND/AIMS:ATP stimulation of purinergic P2 receptors (P2YR and P2XR) regulates several hepatic functions. Here we report the involvement of ATP-mediated signals in enhancing hepatocyte tolerance to lethal stress. METHODS:The protection given by purinergic agonists was investigated in rat hepatocytes exposed to h...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.02.017
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND/AIMS:We tested whether cholesterol gallstone disease (GS) is associated to insulin resistance and serum C-reactive protein (CRP) in a high risk population. METHODS:This was a nested case-control study on 881 Chilean subjects that included clinical examination, abdominal ultrasound and blood chemistries. Ins...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.01.026
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND & AIMS:Living donor liver transplantation (LDLT) provides a timely alternative to deceased donor liver transplantation (DDLT) for patients with hepatitis C virus-related (HCV-related) diseases in the circumstances of severe organ dearth. However, the patient and graft outcomes, and recurrence of HCV after LD...
journal_title:Journal of hepatology
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.jhep.2012.07.015
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND/AIMS:Vaccination strategies able to induce strong T-cell responses might contribute to eradicate hepatitis C virus (HCV) infection. We previously demonstrated that fusion of an antigen to the extra domain A from fibronectin (EDA) targets the antigen to TLR4-expressing dendritic cells (DC) and improves its im...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.06.005
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND & AIMS:Clinical cases of viral infections possibly involving the transfusion of blood components are systematically investigated. METHODS:Serological and molecular markers of hepatitis B virus were used including HBsAg, anti-HBc, anti-HBs, HBV DNA, and viral load. Full genome sequencing and phylogenetic ana...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.07.034
更新日期:2012-03-01 00:00:00
abstract:AIMS:To assess the presence of autonomic neuropathy in patients with non-alcoholic chronic liver disease and its relationships with the severity of liver damage. METHODS:Thirty non-alcoholic patients with chronic liver disease and 26 healthy control subjects were studied. The silicone imprint technique was used to qua...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80458-8
更新日期:1997-06-01 00:00:00
abstract:BACKGROUND/AIMS:Except for bleeding complications, other serious adverse reactions of coumarin anticoagulants such as hepatotoxicity or skin necrosis are comparatively rare. Nonetheless, a small number of coumarin-induced (sub-) acute liver failures has been published. METHODS:A retrospective analysis was performed of...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.03.010
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND/AIMS:Aberrant c-Jun N-terminal kinase (JNK) activation has been linked to hepatocellular carcinoma (HCC) in mouse models. It remains unclear whether JNK activation plays an important role in human HCC and, if so, how JNK signaling contributes to the initiation or progression of HCC. METHODS:The JNK activati...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.07.037
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND/AIM:Smooth muscle antibodies and antinuclear antibodies characterize type 1 autoimmune hepatitis. Our aim was to correlate the appearance and disappearance of these autoantibodies with clinical and histological events. METHODS:One hundred and seven patients were evaluated successively over 128+/-9 months. A...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80096-8
更新日期:1999-03-01 00:00:00
abstract::The circuitous cell signalling pathways of hepatocytes comprise several factors that operate to downgrade or even interrupt the transmission of a given signal. These down-regulating influences are essential to keep cell proliferation and cell survival in check and if impaired, can alter a delicate balance in favour of...
journal_title:Journal of hepatology
pub_type:
doi:10.1016/j.jhep.2007.09.003
更新日期:2007-12-01 00:00:00
abstract::Lactitol is a disaccharide analogue of lactulose which is available as a pure crystalline powder. The efficacy of lactitol in the treatment of chronic hepatic encephalopathy was assessed in 9 cirrhotic patients in a randomised, double-blind, cross-over comparison with lactulose. The sugars were dispensed in solutions,...
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(87)80086-7
更新日期:1987-04-01 00:00:00
abstract::Serotonin or 5-hydroxytryptamine (5-HT) is known to regulate several key aspects of liver biology and these functions include hepatic blood flow, innervation and wound healing. Given the importance of these functions it is surprising that relatively little time has been dedicated to studying the precise function and m...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2008.01.006
更新日期:2008-04-01 00:00:00
abstract:BACKGROUND/AIMS:The aim of this study was to identify human liver proteins that are associated with different stages of liver development. METHODS:We collected liver samples from 14 fetuses between 14 and 41 weeks of development, one child and four adults. Proteins which exhibited consistent and significant variations...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.02.029
更新日期:2009-07-01 00:00:00
abstract:BACKGROUND & AIMS:Visceral adiposity is associated with hepatic steatosis, inflammation, and fibrosis in non-alcoholic fatty liver disease (NAFLD). The visceral adiposity index (VAI), a novel marker of visceral fat distribution and dysfunction, has been correlated with histology in hepatitis C. We assessed the ability ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.03.013
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND/AIMS:The aim of this study is to verify the efficacy and safety of peg-interferon alfa-2b in combination with ribavirin for initial treatment of HCV-associated mixed cryoglobulinemia. METHODS:Eighteen patients (7 women and 11 men) affected by mixed cryoglobulinemia were included in the study and treated wit...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/j.jhep.2004.10.031
更新日期:2005-05-01 00:00:00
abstract::We report a case of chronic active hepatitis caused by benzarone, a benzofuran derivative used in Europe for the treatment of peripheral venous disorders. Jaundice and serum alanine aminotransferase activity increased while drug administration was continued, but promptly decreased when it was eventually interrupted. L...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80039-9
更新日期:1987-12-01 00:00:00
abstract:BACKGROUND/AIMS:5-Aminolevulinic acid (ALA), a precursor of porphyrins is used for photodynamic diagnosis and therapy within topical or systemic applications. A potential toxic effect on the human liver is of major interest and therefore we investigated the impact of a repeated application of ALA without illumination o...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00454-3
更新日期:2003-04-01 00:00:00