Abstract:
BACKGROUND/AIMS:Hepatocellular carcinoma is one of the most malignant tumors in the world. Although a wide range of therapeutic options is available, the efficacy of these methods and the prognosis of hepatocellular carcinoma are still very poor. The nucleoside analogs 2-chlorodeoxyadenosine (Cladribine, 2-CdA) and 2',2'-difluorodeoxycytidine (Gemcitabine, dFdC) have shown potent cytotoxic effects on various human tumor cell lines in vitro and marked therapeutic efficacy in the treatment of lymphoproliferative disorders and several solid tumors in vivo. In the present study we evaluated the antitumor effect of 2-CdA and dFdC on human hepatoma HepG2 cells. METHODS:HepG2 cells were grown in the absence and presence of increasing concentrations of 2-CdA and dFdC. Antitumor activity was assessed by inhibition of cell growth, evaluated by counting cell numbers in a hemocytometer and by 3H-thymidine uptake, and by reduction of cell viability as determined by exclusion of 0.1% trypan blue. For rescue experiments, the natural pyrimidine deoxycytidine (dCyd) was added simultaneously or delayed. RESULTS:A strong antitumor activity was observed for both compounds. dFdC showed a more pronounced effect with an inhibition constant (IC50) of 3.98+/-0.03 nM in comparison to 2-CdA with an IC50 of 16.66+/-0.40 nM. Both drugs achieved their half-maximal antitumor activity after 31 h. With respect to dFdC, fractionated daily administrations showed a distinctly greater antitumor activity than a single transient administration. The cytotoxic effects of 2-CdA and dFdC were completely reversed by simultaneous addition of dCyd. CONCLUSION:In this paper we show strong antitumor effects of the nucleoside analogs 2-CdA and dFdC on the human hepatoma cell line HepG2. These findings suggest that both compounds, but in particular dFdC, are promising substances for further evaluations in the treatment of hepatocellular carcinoma.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Graziadei I,Kelly T,Schirmer M,Geisen FH,Vogel W,Konwalinka Gdoi
10.1016/s0168-8278(98)80326-7subject
Has Abstractpub_date
1998-03-01 00:00:00pages
504-9issue
3eissn
0168-8278issn
1600-0641pii
S0168-8278(98)80326-7journal_volume
28pub_type
杂志文章abstract::Clinical complexity, anatomic diversity and molecular heterogeneity of cholangiocarcinoma (CCA) represent a major challenge in the assessment of effective targeted therapies. Molecular and cellular mechanisms underlying the diversity of CCA growth patterns remain a key issue of clinical concern. Crucial questions comp...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2014.09.007
更新日期:2015-01-01 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:Transcatheter arterial chemoembolization with lipiodol (TACE) is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. It has recently been recommended for patients with 2 or 3 tumors >3 cm or ≥4 tumors in a treatment algorithm proposed by Japanese guideli...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.10.021
更新日期:2012-04-01 00:00:00
abstract::Recent progress in basic research has enhanced our understanding of the molecular mechanisms of normal bile secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause hereditary cholestatic syndromes or determine susceptibil...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2009.05.012
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND/AIMS:The use of cell lines in bioartificial liver support systems (BALSS) to treat fulminant hepatic failure (FHF) is hindered by their reduced metabolic functions, which could be further decreased by the patient's serum/plasma. Hence, the aim of this study was to (i) test the effect of the FHF serum on C3A ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.06.012
更新日期:2004-10-01 00:00:00
abstract:BACKGROUND & AIM:Virus-induced fulminant hepatitis is a major cause of acute liver failure. During acute viral hepatitis the impact of type I interferon (IFN-I) on myeloid cells, including liver-resident Kupffer cells (KC), is only partially understood. Herein, we dissected the impact of locally induced IFN-I responses...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.11.029
更新日期:2018-04-01 00:00:00
abstract:BACKGROUND & AIMS:Repair from biliary damages requires the biliary specification of hepatic progenitor cells and the remodeling of ductular reactive structures into branching biliary tubules. We hypothesized that the morphogenetic role of Notch signaling is maintained during the repair process and have addressed this h...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.02.025
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND & AIMS:Data from clinical trials suggest a potential role for on-treatment monitoring of serum HBsAg titres during interferon-alpha (pegIFN) therapy in predicting virological responses. However, baseline HBsAg titres during the natural history of chronic hepatitis B (CHB) have not been well-characterized. We...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.jhep.2010.01.007
更新日期:2010-04-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatobiliary malignancies are frequently seen in primary sclerosing cholangitis (PSC) and they complicate the evaluation of patients and timing of liver transplantation. METHODS:Data from all Nordic PSC patients listed for liver transplantation during 1990-2001 were recorded prospectively. Predictors ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.01.002
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND & AIMS:Innate sensing of viral infection activates a global defense response including type I interferon (IFN) and IFN-stimulated genes (ISGs) expression. We previously reported that HCV NS3/4A protease, an essential protein in viral polyprotein processing, can abrogate antiviral signaling pathways and effec...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.07.017
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND/AIMS:Recent reports have shown a high frequency of anti-hepatitis C virus antibodies in patients with cryoglobulinemia. The factors involved in the production of cryoglobulins in hepatitis C virus-infected patients are unknown. To assess the role of hepatitis C virus genotypes in the pathogenesis of mixed cr...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80200-5
更新日期:1996-10-01 00:00:00
abstract::Interleukin-6 has a variety of biological effects, mainly on the immune system. The regulation of this signal at both the site of production and the site of action is necessary to maintain the organism's homeostasis. In the microenvironment of the hepatic sinusoids, Kupffer cells as resident macrophages are the most p...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(94)80099-5
更新日期:1994-10-01 00:00:00
abstract:BACKGROUND & AIMS:Diabetes occurring as a direct consequence of loss of liver function is usually characterized by non-diabetic fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) levels and should regress after orthotopic liver transplantation (OLT). This observational, longitudinal study investigated the relatio...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.01.015
更新日期:2019-05-01 00:00:00
abstract::Interferon-alpha therapy has a beneficial effect in 30-40% of selected patients with chronic hepatitis B who respond by clearing hepatitis B e antigen (HBeAg) and hepatitis B viral (HBV) DNA from serum. This is usually associated with normalization of serum aminotransferase activities. On long-term follow-up of treate...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND & AIMS:FibroTest™ (FT) and Transient Elastography (TE) have been validated as non-invasive markers of METAVIR fibrosis stages from F0 to F4 using biopsy, and as prognostic markers of liver related mortality in patients with chronic hepatitis C. The aim was to extend the validation of FT and TE as markers of ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.11.016
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND/AIMS:Recently, a novel DNA virus was isolated from the serum of a patient with post-transfusion non-A-G hepatitis and named TT virus. The aim of this study was to determine the prevalence and clinical characteristics of TT virus infection in patients with sporadic acute hepatitis of unknown etiology. METHOD...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80309-2
更新日期:1999-12-01 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:BACKGROUND/AIMS:To elucidate the mechanisms of action of interferon (IFN) against hepatitis C virus (HCV), we studied the serum HCV dynamics of free-virions (FV) and immune-complexes (IC) in patients treated with IFN. METHODS:FV and IC were separated by immunoprecipitation using anti-human immunoglobulin and quantifie...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00472-0
更新日期:2003-12-01 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::Ciprofloxacin, a fluorinated quinolone, is a powerful antibiotic widely used for its broad spectrum of activity in ambulatory and long-term care setting. Until now, ciprofloxacin administration has been associated with a few cases of acute, sometimes cholestatic jaundice or fulminant hepatic failure believed mainly re...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00268-4
更新日期:2002-11-01 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::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:BACKGROUND/AIMS:Circulatory abnormalities with activation of vasoconstrictor systems after large-volume paracentesis are generally considered secondary to an increased extravasation of fluid from the intravascular compartment to the extravascular space with subsequent reduction in plasma volume. To test this hypothesis...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80081-5
更新日期:1997-10-01 00:00:00
abstract:BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and obesity are epidemiologically correlated with each other but the causal inter-relationships between them remain incompletely understood. We aimed to explore the causal relationships between the 3 diseases. METHODS:Using both UK Biob...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.03.006
更新日期:2020-08-01 00:00:00
abstract::Experimental autoimmune hepatitis was induced in C57BL/6 mice by immunization with syngeneic liver protein and adjuvant. Hepatitis was characterized by marked cellular infiltrates, but hepatic necrosis was mild to moderate. A small dose of endotoxin (25 micrograms/mouse) produced lethal hepatitis with elevation of ser...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80548-3
更新日期:1993-11-01 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: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:BACKGROUND & AIMS:Hepatomegaly can be triggered by insulin and insulin-unrelated etiologies. Insulin acts via AKT, but how other challenges cause hepatomegaly is unknown. METHODS:Since many hepatomegaly-inducing toxicants and stressors activate NRF2, we examined the effect of NRF2 activation on liver size and metaboli...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.01.023
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND/AIMS:The liver is the major source of collagen XVIII (C18), the precursor of the angiogenesis inhibitor endostatin. In human liver C18 is mainly expressed by hepatocytes. However, its quantitative and temporospatial expression patterns during liver fibrogenesis are unknown. METHODS:We used RNA quantificatio...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00134-9
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND & AIMS:Number-needed-to-treat is used in assessing the effectiveness of a health-care intervention, and reports the number of patients who need to be treated to prevent one additional bad outcome. Although largely used in medical literature, there are no studies measuring the benefit of liver transplantation...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.01.022
更新日期:2014-06-01 00:00:00