Abstract:
BACKGROUND & AIMS:Large extracellular vesicles, specifically AnnexinV+ EpCAM+ CD147+ tumour-associated microparticles (taMPs), facilitate the detection of colorectal carcinoma (CRC), non-small cell lung carcinoma (NSCLC) as well as pancreas carcinoma (PaCa). Here we assess the diagnostic value of taMPs for detection and monitoring of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Specifically, the aim of this study was to differentiate liver taMPs from other cancer taMPs, such as CRC and NSCLC. METHODS:Fluorescence-activated cell scanning (FACS) was applied to detect various taMP populations in patients' sera that were associated with the presence of a tumour (AnnexinV+ EpCAM+ CD147+ taMPs) or could discriminate between cirrhosis (due to HCV or HBV) and liver cancers (AnnexinV+ EpCAM+ ASGPR1+ taMPs). In total 172 patients with liver cancer (HCC or CCA), 54 with cirrhosis and no liver neoplasia, and 202 control subjects were enrolled. RESULTS:The results indicate that AnnexinV+ EpCAM+ CD147+ taMPs were elevated in HCC and CCA. Furthermore, AnnexinV+ EpCAM+ ASGPR1+ CD133+ taMPs allowed the distinction of liver malignancies (HCC or CCA) and cirrhosis from tumour-free individuals and, more importantly, from patients carrying other non-liver cancers. In addition, AnnexinV+ EpCAM+ ASGPR1+ taMPs were increased in liver cancer-bearing patients compared to patients with cirrhosis that lacked any detectable liver malignancy. The smallest sizes of successfully detected cancers were ranging between 11-15mm. AnnexinV+ EpCAM+ ASGPR1+ taMPs decreased at 7days after curative R0 tumour resection suggesting close correlations with tumour presence. ROC values, sensitivity/specificity scores and positive/negative predictive values (>78%) indicated a potent diagnostic accuracy of AnnexinV+ EpCAM+ ASGPR1+ taMPs. CONCLUSION:These data provide strong evidence that AnnexinV+ EpCAM+ ASGPR1+ taMPs are a novel biomarker of HCC and CCA liquid biopsy that permit a non-invasive assessment of the presence and possible extent of these cancers in patients with advanced liver diseases. LAY SUMMARY:Microparticles (MPs) are small vesicles that bleb from the membrane of every cell, including cancer cells, and are released to circulate in the bloodstream. Since their surface composition is similar to the surface of their underlying parental cell, MPs from the bloodstream can be isolated and by screening their surface components, the presence of their parental cells can be identified. This way, it was possible to detect and discriminate between patients bearing liver cancer and chronic liver cirrhosis.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Julich-Haertel H,Urban SK,Krawczyk M,Willms A,Jankowski K,Patkowski W,Kruk B,Krasnodębski M,Ligocka J,Schwab R,Richardsen I,Schaaf S,Klein A,Gehlert S,Sänger H,Casper M,Banales JM,Schuppan D,Milkiewicz P,Lammert F,doi
10.1016/j.jhep.2017.02.024subject
Has Abstractpub_date
2017-08-01 00:00:00pages
282-292issue
2eissn
0168-8278issn
1600-0641pii
S0168-8278(17)30123-Xjournal_volume
67pub_type
杂志文章abstract::Data derived from population, case-control, and cohort studies conducted in several Euro-Mediterranean and African countries disclose impressive similarities in the age and modes of hepatitis B virus (HBV) transmission and in the prevalence, duration, and outcome of the four phases of the natural history of chronic in...
journal_title:Journal of hepatology
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.jhep.2010.12.030
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND/AIMS:The x gene of hepatitis B virus encodes a transactivating factor of 154 amino acids, termed HBx, which stimulates transcription of multiple viral and cellular genes. The transactivating function is probably associated with a tumorigenic potential of HBx, since x gene sequences, encoding functional HBx, ...
journal_title:Journal of hepatology
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doi:10.1016/0168-8278(95)80311-4
更新日期:1995-07-01 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:Neonatal sclerosing cholangitis (NSC) is a severe neonatal-onset cholangiopathy commonly leading to liver transplantation (LT) for end-stage liver disease in childhood. Liver biopsy findings histopathologically resemble those in biliary atresia (BA); however, in NSC extrahepatic bile ducts are patent,...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.07.017
更新日期:2016-12-01 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:To evaluate demographic characteristics, liver histology and virological features of hepatitis C virus (HCV) carriers with normal alanine transaminase (ALT) levels. METHODS:A nationwide prospective study was started in 1997. Four Italian centres have participated in this study. RESULTS:Eight hundred a...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00101-0
更新日期:2002-07-01 00:00:00
abstract::A technique is described for the isolation and culture of Kupffer cells (Kc) from needle and surgical liver biopsies of humans and rats. The isolation procedure is based on puncture perfusion of the specimen with collagenase and pronase, and subsequent gradient centrifugation. The ultrastructure of the cultured cells ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(88)80505-1
更新日期:1988-08-01 00:00:00
abstract:BACKGROUND & AIMS:Disturbance in lipid metabolism is one of the features of chronic hepatitis C, being a crucial determinant of the progression of liver fibrosis. Experimental studies have revealed that the core protein of hepatitis C virus (HCV) induces steatosis. METHODS:The activities of fatty acid metabolizing enz...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.07.039
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND/AIMS:We developed a bioartificial liver (BAL) based on a direct hemoperfusion typed nonwoven fabric bioreactor containing porcine hepatocytes. In this study, the efficacy of our BAL was evaluated with a pig fulminant hepatic failure (FHF) model. METHODS:FHF was induced with intravenous administration of D-g...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.08.006
更新日期:2006-02-01 00:00:00
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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::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::In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were significantly (p less t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90859-a
更新日期:1991-07-01 00:00:00
abstract::The presence of hepatitis B virus DNA (HBV-DNA) in the peripheral blood mononuclear cells (PBMC) of 29 anti-HIV symptomless carriers (eleven HBeAg positive, eleven anti-HBe positive and seven HBsAg negative) and of 40 anti-human immunodeficiency virus (HIV)-negative patients (15 HBeAg positive, 15 anti-HBe positive an...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(90)90050-2
更新日期:1990-03-01 00:00:00
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::We describe a new model of submaximal stimulation of liver regeneration in the rat. Removal of the right lateral lobes in the rat produced a 21% hepatectomy. The measurement accuracy of the incorporation rate of [14C]thymidine into DNA 24 h after 21% hepatectomy (n = 32) was less than that after the standard 34% hepat...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90833-w
更新日期:1991-05-01 00:00:00
abstract::Hepatitis viruses are major threats to human health. During the last decade, highly diverse viruses related to human hepatitis viruses were found in animals other than primates. Herein, we describe both surprising conservation and striking differences of the unique biological properties and infection patterns of human...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2018.11.010
更新日期:2019-03-01 00:00:00
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 p...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.08.007
更新日期:2015-01-01 00:00:00
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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::A quantitative immunohistochemical study of Kupffer cells in liver biopsies from alcoholics was carried out. Two markers were compared, lysozyme and an antimacrophage monoclonal antibody EMB/11. The results showed that there is no significant reduction in Kupffer cell numbers in acute and chronic alcoholic liver disea...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(89)90005-6
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abstract:BACKGROUND & AIMS:Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis mainly due to metastasis. MicroRNAs are endogenous small noncoding RNAs that regulate cellular gene expression and are functionally linked to tumourigenesis. Using microarray analysis, we recently identified 20 miRNAs associa...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.12.025
更新日期:2010-05-01 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:Regulatory CD4(+) T cells (Tregs) are considered to affect outcomes of HCV infection, because they increase in number during chronic hepatitis C and can suppress T-cell functions. METHODS:Using microarray analysis, in situ immunofluorescence, ELISA, and flowcytometry, we characterised functional diff...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.04.011
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND & AIMS:The liver is a crucial organ at the crossroads of iron and glucose metabolism. The aim of the study was to assess intra-hepatic iron in young patients with non-alcoholic fatty liver disease (NAFLD) and its association with insulin resistance and severity of liver damage. METHODS:Intrahepatic iron con...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.12.007
更新日期:2011-09-01 00:00:00
abstract::One hundred and eight patients with cirrhosis (23 grade A, 46 grade B and 39 grade C, according to Pugh's classification) underwent hemodynamic studies and plasma catecholamine concentration measurements. Blood samples were withdrawn from the pulmonary artery (n = 108), the hepatic vein (n = 108), the azygos vein (n =...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90810-x
更新日期:1991-09-01 00:00:00
abstract:BACKGROUND & AIMS:The presence of multifocal tumors, developed either from intrahepatic metastasis (IM) or multicentric occurrence (MO), is a distinct feature of hepatocellular carcinoma (HCC). Immunogenomic characterization of multifocal HCC is important for understanding immune escape in different lesions and develop...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.12.014
更新日期:2020-05-01 00:00:00
abstract:BACKGROUND & AIMS:The mechanisms of treatment resistance to interferon (IFN) and ribavirin (Rib) combination therapy for hepatitis C virus (HCV) infection are not known. This study aims to gain insight into these mechanisms by exploring hepatic gene expression before and during treatment. METHODS:Liver biopsy was perf...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.036
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND/AIMS:Failure to induce apoptosis triggered by members of the death receptor family has been described in hepatocellular carcinoma (HCC) and sensitization of malignant cells to pro-apoptotic molecules such as TRAIL has been proposed as an alternative cancer therapy. Limiting to this approach are the resistanc...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.10.010
更新日期:2007-04-01 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:Macrophages (Mϕ) represent a major component of tumor tissues and play an important role in both tumor progression and therapeutic response. Although tumor Mϕ are generally considered to be derived from circulating monocytes, emerging evidence indicates that tissue Mϕ pools can be maintained by self-r...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.10.021
更新日期:2020-10-31 00:00:00
abstract:BACKGROUND/AIM:Endothelin-1 plays an important role in the regulation of portal hypertension; endothelin antagonists have been extensively studied in portal hypertensive animals. We aimed to evaluate the efficacy of highly selective endothelin antagonists in partial portal vein ligated (PPVL) rats. METHODS:Four groups...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80303-7
更新日期:2000-11-01 00:00:00