Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the past 10 years we have witnessed an exponential increase in the knowledge on the development and progression of liver fibrosis. At present, liver fibrogenesis is referred to as a dynamic process involving complex cellular and molecular mechanisms, resulting from the chronic activation of the tissue repair mechanisms that follows reiterated liver tissue injury. The identification and characterization of the cell types and of the different mediators involved in this process has allowed a "revisitation" of several issues related to liver cirrhosis and its immediate consequences. Among these, evaluation of the relationships occurring between fibrogenesis and portal hypertension, cholestasis, and the development of hepatocellular carcinoma represent some of the hottest areas of research in the field of hepatology. Our aim is to establish a link between the available knowledge on the biology of hepatic stellate cells and their possible implication in the genesis and progression of portal hypertension.
 ...
PMID:Biology of hepatic stellate cells and their possible relevance in the pathogenesis of portal hypertension in cirrhosis. 1064 25

Occasional side-effects of transcatheter arterial chemoembolization therapy in hepatocellular carcinoma are essentially related to tissue necrosis. We report the case of a patient with hepatocellular carcinoma who experienced an acute common bile duct obstruction a few weeks after such a procedure, in the absence of obvious biliary tract invasion. An endoscopic sphincterotomy relieved the obstruction. At histology, the intra-biliary material was identified as a fragment of hepatocellular carcinoma. We discuss the causes of obstructive jaundice in the setting of hepatocellular carcinoma as well as in the specific situation of transcatheter arterial chemoembolization therapy.
 ...
PMID:Biliary migration of hepatocellular carcinoma fragment after transcatheter arterial chemoembolization therapy. 1074 42

Liver injury during cholestasis reflects a balance between the effects of toxic and nontoxic bile acids. However, the critical distinction between a toxic and nontoxic bile acid remains subtle and unclear. For example, the glycine conjugate of chenodeoxycholate (GCDC) induces hepatocyte apoptosis, whereas the taurine conjugate (TCDC) does not. We hypothesized that the dissimilar cellular responses may reflect differential activation of a phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway. In the bile acid-transporting McNtcp.24 rat hepatoma cell line, TCDC, but not GCDC, stimulated PI3K activity. Consistent with this observation, inhibition of PI3K rendered TCDC cytotoxic, and constitutive activation of PI3K rendered GCDC nontoxic. Both Akt and the atypical protein kinase C isoform zeta (PKCzeta) have been implicated in PI3K-dependent survival signaling. However, TCDC activated PKCzeta, but not Akt. Moreover, inhibition of PKCzeta converted TCDC into a cytotoxic agent, whereas overexpression of wild-type PKCzeta blocked GCDC-induced apoptosis. We also demonstrate that TCDC activated nuclear factor kappaB (NF-kappaB) in a PI3K- and PKCzeta-dependent manner. Moreover, inhibition of NF-kappaB by an IkappaB super-repressor rendered TCDC cytotoxic, suggesting that NF-kappaB is also necessary to prevent the cytotoxic effects of TCDC. Collectively, these data suggest that some hydrophobic bile acids such as TCDC activate PI3K-dependent survival pathways, which prevent their otherwise inherent toxicity.
 ...
PMID:The bile acid taurochenodeoxycholate activates a phosphatidylinositol 3-kinase-dependent survival signaling cascade. 1077 Sep 53

Knowledge on the development and progression of liver fibrosis has grown exponentially in the past decade. At present, liver fibrogenesis is referred to as a dynamic process involving complex cellular and molecular mechanisms, resulting from the chronic activation of the tissue repair mechanisms that follows reiterated liver tissue injury. The identification and characterization of the cell types and of the different mediators involved in this process has allowed a "re-visitation" of several issues related to liver cirrhosis and its immediate consequences. Among these, evaluation of the relationships occurring between fibrogenesis and portal hypertension, cholestasis and the development of hepatocellular carcinoma, represent some of the hottest areas of research in this field of hepatology. The elucidation of many of the cellular and molecular mechanisms responsible for the progression of liver fibrosis has provided a sound basis for the development of pharmacological strategies able to modulate this important pathophysiological process.
 ...
PMID:Liver fibrosis. 1094 37

A 65-year-old man presented with multiple liver tumours. Imaging techniques could not differentiate between adenomas and hepatocellular carcinomas. He had no relevant past medical history. Liver function tests were normal except for a 1.5-fold rise in GGT. AFP was normal. Viral markers were negative. During laparoscopy, numerous black tumours of different sizes were seen. These tumours were adenomas without malignant transformation. Tumoral hepatocytes contained a brown pigment in the canalicular area without evidence of cholestasis. This pigment was Fontana positive and looked like Dubin-Johnson pigment by electron microscopy. The expression of the canalicular multispecific organic anion transporter (cMOAT) was decreased in the tumours but normal in the non-tumoral liver ruling out the diagnosis of Dubin-Johnson syndrome. There was mild iron deposition possibly related to an homozygous H63D mutation in the HFE gene. Three years after their discovery, the size of the tumours remained stable. It is concluded that this male patient with multiple adenomas and mild iron overload is at risk of developing an hepatocellular carcinoma and that the black colour of adenomas is probably due to a partial defect in excretion of organic anions.
 ...
PMID:Multiple black hepatocellular adenomas in a male patient. 1111 85

Alagille syndrome is a rare inherited condition, which typically manifests during the first year of life as an episode of prolonged cholestasis. Although the pattern of inheritance is autosomal dominant with almost complete penetrance, highly variable expression may delay the diagnosis, and with passing time the clinical findings may be more difficult to recognize. This has clinical implications, as patients with Alagille syndrome are at risk for late complications such as hepatocellular carcinoma. We report a case of a 35-yr-old patient with Alagille syndrome who was diagnosed with colonic polyposis raising the possibility of an association between the two.
 ...
PMID:Alagille syndrome with colonic polyposis. 1156 11

gamma-GT is a membrane-bound enzyme which plays a role in the metabolism of glutathione and facilitates amino-acid transport. gamma-GT is located in several tissues such as the kidney, pancreas and liver. Serum gamma-GT activity is induced by hepatobiliary diseases, especially alcoholic liver diseases and cholestasis, not by renal diseases. Isoenzymes specific for hepatocellular carcinoma are demonstrated by electrophoresis. A new method of measuring serum gamma-GT specific for hepatocellular carcinoma was recently reported.
 ...
PMID:[Gamma-glutamyltranspeptidase (gamma-GT)]. 1179 81

A rare autopsy case of hepatocellular carcinoma (HCC) presenting as extrahepatic bile duct obstruction is reported. A 54-year-old man who had been treated at another hospital for obstructive jaundice was referred to our hospital and admitted on March 1, 1998, because of progressive jaundice. On hospital day 94, he died of bleeding esophageal varices. At autopsy, a bile duct tumor, measuring 3.0 x 3.5 cm and adhering to the wall of the left hepatic duct, occluded the common hepatic duct at the hilus. A tumor measuring 2.0 x 2.0 cm was found in the parenchyma of the left liver lobe. The parenchymal tumor was not continuous with the extrahepatic bile duct tumor. Histologically, the bile duct tumor and the parenchymal tumor of the left lobe were diagnosed as HCC. The bile duct tumor was attached to the mucosa of the bile duct with a thin stalk. No invasive growth into the submucosa was observed. The tumor may have been an intrabiliary transplantation from the HCC in the left lobe via the bile duct.
 ...
PMID:Biliary obstruction caused by intrabiliary transplantation from hepatocellular carcinoma. 1182 2

Elevated serum and tissue bilirubin concentrations that occur in pathological conditions such as cholestasis, jaundice, and other liver diseases are known to stimulate cytotoxic responses. In preliminary studies, we noted that bilirubin seemed to cause apoptosis in murine hepatoma Hepa 1c1c7 wild-type (WT) cells. Consequently, we investigated apoptosis caused by bilirubin in WT, mutant C12 [aryl hydrocarbon receptor (AHR)-deficient], and C4 (AHR nuclear translocator-deficient) Hepa 1c1c7 cells. Three independent measures of apoptosis were used to quantify the effects of exogenous bilirubin (0, 1, 10, 25, 50, or 100 microM). Caspase-3 activity and cytochrome c release from mitochondria increased at 3 h post-treatment, before increased caspase-8 activity at 6 h, and nuclear condensation by 24 h after treatment with bilirubin. No differences in whole-cell lipid peroxidation were observed between the cell types; however, intracellular reactive oxygen species (ROS) production was greater in WT cells than C12 or C4 cells 3 h after bilirubin exposure. Pretreatment of cells for 1 h with 1 or 10 microM alpha-naphthoflavone, an AHR antagonist, before bilirubin exposure resulted in decreased caspase-3 activity at 6 h and nuclear condensation at 24 h in WT cells. These results indicate that bilirubin, a potential AHR ligand, causes apoptosis in murine Hepa 1c1c7 WT cells by a mechanism(s) partially involving the AHR, disruption of membrane integrity, and increased intracellular ROS production.
 ...
PMID:Apoptosis in murine hepatoma hepa 1c1c7 wild-type, C12, and C4 cells mediated by bilirubin. 1213 Jun 76

Endotoxin-mediated cholestasis stems from impaired hepatobiliary transport of bile acids and organic anions due to altered expression and activity of transporters, including Oatp, Mrp, Ntcp, and Bsep. However, the mechanisms by which the Oatp and Mrp genes are down-regulated are largely unknown. Using in vivo and in vitro murine models of inflammation, we examined the role of cytokines and bile acids in regulating Oatp and Mrp. Endotoxin (lipopolysaccharide, LPS), interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, cholic acid, taurocholate, or taurodeoxycholate was administered in vivo to mice or in vitro to Hepa 1-6 mouse hepatoma cells. Mrp, Oatp, and Bsep mRNA levels were measured by reverse transcription-polymerase chain reaction. Mrp efflux activity was measured using 5-carboxyfluorescein. In vivo, LPS treatment profoundly suppressed hepatic mRNA levels of Mrp2, Mrp3, Oatp1, Oatp2, and Bsep to 15, 60, 44, 30, and 32% of controls, respectively (p < 0.05), but did not significantly alter Mrp1 expression. IL-6 or IL-1beta administration suppressed Mrp2, Oatp1, Oatp2, and Bsep mRNA levels to 20 to 60% controls (p < 0.05). TNF-alpha administration affected mRNA levels of Mrp2, Mrp3, and Oatp2 but not Oatp1 or Bsep. Bile acid treatment increased the in vivo expression of Bsep but not Mrp or Oatp. Likewise, significantly lower mRNA levels of Mrp2 with a corresponding decrease in cellular efflux of 5-carboxyfluorescein was seen in vitro in IL-6- and IL-1beta-treated Hepa 1-6 cells, whereas bile acids did not have significant effects. In conclusion, cytokines are key mediators in regulating hepatic expression of anion transporters in inflammatory cholestasis, whereas bile acids likely play a minor role.
 ...
PMID:Inflammatory cytokines, but not bile acids, regulate expression of murine hepatic anion transporters in endotoxemia. 1223 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>