Search results for "Liver Neoplasms."
showing 10 items of 733 documents
Malignant transformation of the liver tumour precursor cell line OC/CDE 22 by the four stereoisomeric fjord region 3,4-dihydrodiol 1,2-epoxides of be…
1995
In previous work we established the rat liver oval cell line OC/CDE 22 in order to study in vitro mechanisms of liver cell transformation. We have now exposed OC/CDE 22 cells to each of the four optically active fjord region dihydrodiol epoxides of benzo[c]phenanthrene to investigate their capacity for malignant transformation of liver cells. All four configurational isomers, which are among the most potent carcinogenic metabolites of polycyclic aromatic hydrocarbons tested in murine tumour models, malignantly transform OC/CDE 22 cells at a 2 microM dose level, resulting in a similar colony-forming efficiency in soft agar. Inoculation of the transformed cells into newborn syngeneic rats pro…
Application of patient-derived liver cancer cells for phenotypic characterization and therapeutic target identification.
2018
Primary liver cancer (PLC) ranks among the most lethal solid cancers worldwide due to lack of effective biomarkers for early detection and limited treatment options in advanced stages. Development of primary culture models that closely recapitulate phenotypic and molecular diversities of PLC is urgently needed to improve the patient outcome. Long-term cultures of 7 primary liver cancer cell lines of hepatocellular and cholangiocellular origin were established using defined culture conditions. Morphological and histological characteristics of obtained cell lines and xenograft tumors were analyzed and compared to original tumors. Time course analyses of transcriptomic and genomic changes were…
The novel NF-κB inhibitor DHMEQ synergizes with celecoxib to exert antitumor effects on human liver cancer cells by a ROS-dependent mechanism
2012
In a previous work of ours dehydroxymethyl-epoxyquinomicin (DHMEQ), an inhibitor of NF-κB, was shown to induce apoptosis through Reactive Oxygen Species (ROS) production in hepatoma cells. The present study demonstrated that DHMEQ cooperates with Celecoxib (CLX) to decrease NF-κB DNA binding and to inhibit cell growth and proliferation more effectively than treatment with these single agents alone in the hepatoma cell lines HA22T/VGH and Huh-6. ROS production induced by the DHMEQ-CLX combination in turn generated the expression of genes involved in endoplasmic reticulum (ER) stress and silencing TRB3 mRNA significantly decreased DHMEQ-CLX-induced cell growth inhibition. Moreover, the DHMEQ-…
Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction
2006
Abstract Background Hepatocelluar carcinoma (HCC) is one of the most common cancers worldwide and a major cause of cancer-related mortality. HCC is highly resistant to currently available chemotherapeutic drugs. Defects in apoptosis signaling contribute to this resistance. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 protein family which interferes with mitochondrial activation. In a previous study we have shown that Mcl-1 is highly expressed in tissues of human HCC. In this study, we manipulated expression of the Mcl-1 protein in HCC cells by RNA interference and analyzed its impact on apoptosis sensitivity of HCC cells in vitro. Methods RNA interference was per…
Hepatitis C Virus Core Protein Inhibits Tumor Suppressor Protein Promyelocytic Leukemia Function in Human Hepatoma Cells
2005
Abstract Tumor suppressor protein promyelocytic leukemia (PML) is implicated in apoptosis regulation and antiviral response. PML localizes predominantly to PML-nuclear bodies (PML-NB), nuclear macromolecular complexes regulating tumor suppressor protein p53 activity. Consistent with the function of PML in the cellular antiviral response, PML-NBs represent preferential targets in viral infections. In the case of hepatitis C virus (HCV) infection, important characteristics are nonresponsiveness to IFN therapy and development of hepatocellular carcinoma. However, the mechanisms which lead to the development of hepatocellular carcinoma are largely unknown. Here, we show that HCV core protein lo…
Downregulation of wild-type β-catenin expression by interleukin 6 in human hepatocarcinoma HepG2 cells: a possible role in the growth-regulatory effe…
2001
We investigated the antitumour effects of interleukin 6 (IL-6) on hepatocarcinoma HepG2 cells, endowed with high levels of a mutated, non-degradable, beta-catenin. IL-6 produced minimal growth-inhibitory effects and no apoptosis or gross changes in cell adhesion. Interestingly, however, it caused a consistent decrease in the cytoplasmic levels of wild-type, but not of mutated, beta-catenin protein. There was no effect on E-cadherin or gamma-catenin and a reduction in alpha-catenin occurred only at high concentrations. IL-4, a non-related cytokine, did not modify the content of beta-catenin. IL-6 did not influence beta-catenin mRNA levels. LiCl, a potent inhibitor of Glycogen Synthase Kinase…
Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relat…
2005
The hepatic cancer HA22T/VGH cell line, which constitutively expresses activated nuclear factor-kappaB (NF-kB), was chosen as a model to examine the antitumor activity of curcumin, also in relationship to its possible influences on the activation of the transcription factor and on the expression of the inhibitory of apoptosis proteins (IAPs) and of other NF-kB target genes. Curcumin exerted cell growth inhibitory and apoptotic effects, related, at least part, to free radical generation and mainly dependent on caspase-9 and -3 activation. The combination of curcumin with cisplatin resulted in a synergistic antitumor activity and that with doxorubicin in additivity or sub-additivity. Curcumin…
Transcriptomic responses generated by hepatocarcinogens in a battery of liver-based in vitro models
2013
As the conventional approach to assess the potential of a chemical to cause cancer in humans still includes the 2-year rodent carcinogenicity bioassay, development of alternative methodologies is needed. In the present study, the transcriptomics responses following exposure to genotoxic (GTX) and non-genotoxic (NGTX) hepatocarcinogens and non-carcinogens (NC) in five liver-based in vitro models, namely conventional and epigenetically stabilized cultures of primary rat hepatocytes, the human hepatoma-derived cell lines HepaRG and HepG2 and human embryonic stem cell-derived hepatocyte-like cells, are examined. For full characterization of the systems, several bioinformatics approaches are emp…
The Peroxisome Proliferator WY-14,643 Promotes Hepatocarcinogenesis Caused by Endogenously Generated Oxidative DNA Base Modifications in Repair-Defic…
2007
Abstract Basal levels of endogenously generated oxidative DNA modifications such as 7,8-dihydro-8-oxoguanine (8-oxoG) are present in apparently all mammalian cells, but their relevance for the generation of spontaneous cancers remains to be established. Both the 8-oxoG levels and the resulting spontaneous mutations are increased in the livers of Csbm/m/Ogg1−/− mice, which are deficient in the repair of 8-oxoG. In order to determine the consequences of these additional oxidative DNA modifications and mutations and thus assess the tumor initiating potency of this type of endogenous DNA damage, we treated Csbm/m/Ogg1−/− mice and repair-proficient controls with the peroxisome proliferator WY-14…
Challenges and new prospects in hepatosplenic γδ T-cell lymphoma.
2014
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoid neoplasms characterized by aggressive clinical behavior and dismal prognosis. Hepatosplenic γδ T-cell lymphoma (γδ-HSTL) is a particular form of PTCL that arises from a small subset of γ/δ T-cell receptor-expressing lymphocytes. γδ-HSTL has a rapidly progressive course and poor outcome due also to its refractoriness to conventional chemotherapy regimens. The very low incidence of γδ-HSTL, along with its propensity to mimic different pathological entities, makes this lymphoma a true diagnostic challenge. In this review, we highlight the biological and clinical features of γδ-HSTL that contribute to making this lymphoma…