Abstract:
:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and its burden is expected to increase further in the next years. In spite of the advances of classical therapies, such as surgery, transplantation, use of radiofrequency and transarterial embolization, the prognosis of this neoplasm has not considerably improved over the past few years. The advent of targeted therapies and the approval of the systemic treatment of advanced HCC with the kinase inhibitor sorafenib have provided some hope for the future. Even if the molecular mechanisms responsible for the onset and progression of HCC are still largely unknown, new therapeutic targets have recently come to the spotlight. One of these targets is the tyrosine kinase receptor for the Hepatocyte Growth Factor, encoded by the MET gene, known to promote tumor growth and metastasis in many human organs. In this review we will summarize the contrasting results obtained in vitro (in HCC cell lines) and in animal experimental models and we will also try to analyze the reasons for the opposite findings, suggesting that the HGF/MET axis can have either a promoting or a suppressive role in the development of HCC. We will also reconsider the evidence of activation of this pathway in human HCCs and discuss the results of the clinical trials performed with MET inhibitors. The final purpose is to better clarify which can be the role of MET as a therapeutic target in HCC.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Giordano S,Columbano Adoi
10.1016/j.jhep.2013.09.009subject
Has Abstractpub_date
2014-02-01 00:00:00pages
442-52issue
2eissn
0168-8278issn
1600-0641pii
S0168-8278(13)00661-2journal_volume
60pub_type
杂志文章,评审abstract:BACKGROUND/AIMS:Interleukin-15 (IL-15) is expressed in many organs. It generally inhibits apoptosis and increases cellular proliferation and differentiation. However, IL-15's roles in liver are unknown. We aimed to determine if IL-15 influences hepatic integrity and regenerative activity. METHODS:Expression of IL-15 a...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.04.008
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND & AIMS:Surgery in cirrhosis is associated with a high morbidity and mortality. Retrospectively reported prognostic factors include emergency procedures, liver function (MELD/Child-Pugh scores) and portal hypertension (assessed by indirect markers). This study assessed the prognostic role of hepatic venous pr...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2019.07.007
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND/AIMS:S-adenosylmethionine (SAM) is a thiol-containing compound with known therapeutic affects on cholestasis and hepatotoxicity. The aim of this study was to investigate the effect of SAM on the prevention of mitochondrial injury induced by hepatic ischemia and reperfusion. METHODS/RESULTS:Rats were subject...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)00045-3
更新日期:2001-03-01 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::HCV infection is a global health problem that affects 170 million people worldwide. The severity of the disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma (HCC). Recently, the standard of care for genotype 1 patients has greatly improved with the addition of protease inhibitor...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2012.05.016
更新日期:2012-11-01 00:00:00
abstract::Tissue stress and cell death result in inflammation even in the absence of pathogens. Such sterile inflammation is dependent on a cytosolic complex of proteins inside immune cells termed the inflammasome. This complex converts two groups of extracellular signals into an inflammatory response via activation of caspase-...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.12.017
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND & AIMS:Autophagy plays a crucial role in hepatic homeostasis and its deregulation has been associated with chronic liver disease. However, the effect of autophagy on the release of fibrogenic extracellular vesicles (EVs) by platelet-derived growth factor (PDGF)-stimulated hepatic stellate cells (HSCs) remain...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.04.044
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND/AIMS:We have previously shown that an abnormality in cardiac autonomic reflexes (AN) is an independent predictor of mortality in patients with chronic liver disease. Aim of this study was to determine whether there was an association between prolonged QTc interval and cardiac AN. METHODS:Cardiac AN and QTc ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00217-3
更新日期:2001-12-01 00:00:00
abstract:BACKGROUND/AIMS:Orthotopic liver transplantation has been shown to improve survival in fulminant hepatic failure. However, after orthotopic liver transplantation life-long immunosuppression is necessary and graft complications may occur. METHODS:We employed heterotopic auxiliary liver transplantation in a 26-year-old ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80323-8
更新日期:1995-08-01 00:00:00
abstract::Progressive familial intrahepatic cholestasis 2 is an autosomal-recessive disorder caused by mutations in the ABCB11 gene, which encodes the bile salt export pump (BSEP). Recurrence of BSEP deficiency after liver transplantation is caused by the development of anti-BSEP antibodies. Antibody-induced BSEP deficiency is ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.06.003
更新日期:2018-10-01 00:00:00
abstract:BACKGROUND & AIMS:It was recently shown that semi-annual surveillance for hepatocellular carcinoma (HCC) in cirrhotic patients provides a prognostic advantage over the annual program; however, its cost-effectiveness (CE) in the general cirrhotic population still needs to be defined. METHODS:A Markov model was built to...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2011.11.022
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND/AIM:The present in vivo study investigated the impact of a monoclonal antibody directed against the intercellular adhesion molecule-1 (ICAM-1) on initial microvascular reperfusion injury after liver transplantation. METHODS:Orthotopic, syngeneic liver transplantation including arterial reconstruction was pe...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80252-4
更新日期:2000-05-01 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:The therapeutic option for patients with chronic hepatitis delta virus infection (CHD) is limited to interferon alpha with rare curative outcome. Myrcludex B is a first-in-class entry inhibitor inactivating the hepatitis B virus (HBV) and hepatitis D virus (HDV) receptor sodium taurocholate co-transpo...
journal_title:Journal of hepatology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jhep.2016.04.016
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND & AIMS:Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified. METHODS:We used wild type mice and m...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.01.006
更新日期:2013-05-01 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:Steatohepatitis (SH) is associated with mitochondrial dysfunction and excessive production of superoxide, which can then be converted into H(2)O(2) by SOD2. Since mitochondrial GSH (mGSH) plays a critical role in H(2)O(2) reduction, we explored the interplay between superoxide, H(2)O(2), and mGSH in n...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.05.024
更新日期:2012-10-01 00:00:00
abstract::Twenty patients with paracetamol(acetaminophen)-induced acute liver damage of varying severity were studied longitudinally with assessment of clinical state, standard liver function tests and radiometric hyaluronate (HYA) assay (Pharmacia). In patients (n = 6) who developed coma, HYA rose rapidly with clinical deterio...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90856-7
更新日期:1991-07-01 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::Surveillance of patients at risk of developing hepatocellular carcinoma (HCC) is based on ultrasound (US) examinations performed at either 6 or 12 month intervals. Early detection of HCC in patients with cirrhosis is a challenging issue, since the different entities that are involved in the multi-step process of hepat...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2008.02.005
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND/AIMS:Most hepatocellular carcinomas are still discovered at an advanced stage and are left untreated as large hepatocellular carcinomas are contraindications to liver transplantation and percutaneous ethanol injection and are usually considered as poor indications for liver resection. The aim of this study w...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80319-5
更新日期:1999-12-01 00:00:00
abstract::The presence of HBV-DNA sequences was evaluated in DNA extracted from serum samples, peripheral blood lymphocytes and liver biopsy specimens of five HBsAg/anti-HBe-positive carriers with chronic HDV infection. DNAs were tested by polymerase chain reaction (PCR) amplification technique using two pairs of oligonucleotid...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90032-7
更新日期:1991-01-01 00:00:00
abstract::The First European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected Patients aimed to produce recommendations that could be applied across Europe. However, some important differences exist around Europe, in terms of access to treatment and tests for monitoring. This short survey of...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2005.11.034
更新日期:2006-01-01 00:00:00
abstract::The case for using emergency liver transplantation in acute liver failure was made two decades ago by a series of single centre experiences. The development of models identifying a poor prognosis assisted the selection of patients for liver transplantation but none of these delivers both high sensitivity and specifici...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2013.10.024
更新日期:2014-03-01 00:00:00
abstract::Two patients presented with neonatal cholestasis and acholic stools as first manifestations of McCune-Albright syndrome. Both went through an extensive evaluation including an exploratory laparotomy with peroperative cholangiography which ruled out biliary atresia. One patient presented from the fourth month of life w...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80202-0
更新日期:2000-01-01 00:00:00
abstract::Interleukin-2, a product of helper T cells, is essentially involved in the regulation of cell-mediated immunity. Two monocyte-derived factors, interleukin-1 and prostaglandin E2, influence interleukin-2 synthesis with opposite actions. To analyse immunoregulatory function in HBsAg-positive chronic active hepatitis, T ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80059-4
更新日期:1987-08-01 00:00:00
abstract:BACKGROUND/AIMS:Intrahepatic cholestasis of pregnancy is characterized by pruritus and increased levels of serum bile acids, and is often associated with premature delivery, fetal distress, and perinatal mortality. The aims of the present study were: (i) to better define the serum bile acid profile in intrahepatic chol...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(98)80207-9
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND & AIMS:Hallmarks of non-alcoholic fatty liver disease (NAFLD) are increased triglyceride accumulation within hepatocytes. The prevalence of NAFLD increases steadily with increasing thyrotropin (TSH) levels. However, the underlying mechanisms are largely unknown. Here, we focused on exploring the effect and m...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.06.037
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND/AIMS:The world-wide distribution of hepatitis B virus (HBV) genotypes follows a geographic pattern under the influence of ethnic background. METHODS:Forty eight core genes from four pacific islands were compared with the following findings. RESULTS:First, island-specific variant substitutions were found fo...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.03.025
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND/AIMS:We evaluated the test performance profile (TPP) of blood tests of liver fibrosis. METHODS:Three hundred and fifty-six patients with C chronic hepatitis were included in two centers. Metavir staging of liver specimens by two independent pathologists and the following tests were evaluated: Fibrotest (FT)...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.09.020
更新日期:2007-03-01 00:00:00