Search results for "Liver Neoplasms."
showing 10 items of 733 documents
Apoptosis and the liver
2000
Regulation of the homeostatic balance between cell proliferation and programmed cell death, apoptosis, is essential for development and maintenance of multicellular organisms. Apoptosis is a genetically and evolutionarily highly conserved process. Analysis of the molecular mechanisms of apoptosis has led to a better understanding of many human diseases. Notably in cancer, but also in infectious or autoimmune disease, a deficiency in apoptosis is one of the key events in pathophysiology. On the other hand, overefficient apoptosis, as observed in fulminant liver failure, may be equally harmful for the organism indicating that a tight regulation of the apoptotic machinery is essential for surv…
JNK and AP-1 mediate apoptosis induced by bortezomib in HepG2 cells via FasL/caspase-8 and mitochondria-dependent pathways
2006
The proteasome inhibitor bortezomib is an efficacious apoptotic agent in many tumor cells. This paper shows that bortezomib induced apoptosis in human hepatoma HepG2 cells associated with many modifications in the expression of survival or death factors. Although bortezomib increased the level of the protective factors HSP70 and HSP27, the effects of the drug that favour cell death were predominant. These events include accumulation of c-Jun, phospho-c-Jun and p53; increase in FasL level with activation of caspase-8; changes related to members of Bcl-2 family with increase in the level of pro-apoptotic members and decrease in that of anti-apoptotic ones; dissipation of mitochondrial potenti…
Chronic inflammatory IFN-γ signaling suppresses hepatocarcinogenesis in mice by sensitizing hepatocytes for apoptosis.
2011
Abstract Chronic liver inflammation is a critical component of hepatocarcinogenesis. Indeed, inflammatory mediators are believed to promote liver cancer by upholding compensatory proliferation of hepatocytes in response to tissue damage. However, inflammation can also mediate the depletion of malignant cells, but the difference between tumor-suppressive and tumor-promoting inflammation is not defined at the molecular level. Here, we analyzed the role of the major inflammatory mediator IFN-γ in chemical hepatocarcinogenesis of transgenic mice that overexpress IFN-γ in the liver; these mice manifest severe chronic inflammatory liver damage and lasting compensatory regeneration. We found that …
Sodium butyrate induces apoptosis in human hepatoma cells by a mitochondria/caspase pathway, associated with degradation of beta-catenin, pRb and Bcl…
2004
Butyrate can promote programmed cell death in a number of tumour cells in vitro. This paper provides evidence that butyrate induces apoptosis in human hepatoma HuH-6 and HepG2 cells but is ineffective in Chang liver cells, an immortalised non-tumour cell line. In both HuH-6 and HepG2 cells, apoptosis appeared after a lag period of approximately 16 h and increased rapidly during the second day of treatment. In particular, the effect was stronger in HuH-6 cells, which were, therefore, chosen for ascertaining the mechanism of butyrate action. In HuH-6 cells, beta-catenin seemed to exert an important protective role against apoptosis, since pretreatment with beta-catenin antisense ODN reduced t…
Refining sorafenib therapy: lessons from clinical practice
2015
ABSTRACT Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symp…
Next-Generation Genomic Profiling of Hepatocellular Adenomas: A New Era of Individualized Patient Care
2014
Hepatocellular adenomas (HCAs) are clinically relevant benign liver lesions that commonly occur in women on hormonal contraceptives. In this issue of Cancer Cell, Pilati and colleagues present an integrative multi-“omics”-based analysis of HCA and identify recurrent genetic alterations associated with adenoma-carcinoma transition and new drugable targets.
[The activation of methionine for transmethylation in regenerating rat liver and hepatoma].
1958
The activity of methionine-activating enzyme has been measured in normal and regenerating rat liver and in hepatoma cells.
Polychlorinated biphenyls, classified as either phenobarbital- or 3-methylcholanthrene-type inducers of cytochrome P-450, are both hepatic tumor prom…
1986
Abstract The cytochrome P -450 isozymes, cytochrome P -450 MC 1 and MC 2 , purified from rats treated with 3-methylcholanthrene (MC), were found by immunohistochemical staining to be strongly induced in the livers of rats treated with 3,3′, 4,4′-tetrachlorobiphenyl (TCBP), while the cytochrome P -450 isozymes, PB 1 and PB 2 , purified from the livers of rats treated with phenobarbital (PB), were shown to be induced in the livers of rats treated with 2,2′, 4,4′, 5,5′-hexachlorobiphenyl (HCBP). The latter compound also strongly induced NADPH-cytochrome P -450-reductase. Following induction, all 5 enzymes were located preferentially in the centrilobular and midzonal region of the liver acinus.…
TCDD-dependent downregulation of gamma-catenin in rat liver epithelial cells (WB-F344).
2002
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is the most potent tumor promoter ever tested in rodents. Although it is known that most of the effects of TCDD are mediated by binding to the aryl hydrocarbon receptor (AHR), the mechanisms leading to tumor promotion still remain to be elucidated. Loss of contact-inhibition is a characteristic hallmark in tumorigenesis. In WB-F344 cells, TCDD induces a release from contact-inhibition manifested by a 2- to 3-fold increase in DNA-synthesis and the emergence of foci when TCDD (1 nM) is given to confluent cells. We focussed our interest on potential cell membrane proteins mediating contact-inhibition in WB-F344 cells, namely E-cadherin, alpha,- beta,-…
Cyclooxygenase-2 inhibition induces apoptosis signaling via death receptors and mitochondria in hepatocellular carcinoma.
2006
AbstractInhibition of cyclooxygenase (COX)-2 elicits chemopreventive and therapeutic effects in solid tumors that are coupled with the induction of apoptosis in tumor cells. We investigated the mechanisms by which COX-2 inhibition induces apoptosis in hepatocellular carcinoma (HCC) cells. COX-2 inhibition triggered expression of the CD95, tumor necrosis factor (TNF)-R, and TNF-related apoptosis-inducing ligand (TRAIL)-R1 and TRAIL-R2 death receptors. Addition of the respective specific ligands further increased apoptosis, indicating that COX-2 inhibition induced the expression of functional death receptors. Overexpression of a dominant-negative Fas-associated death domain mutant reduced COX…