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)

This study was aimed at assessing the presence of c-met overexpression in human hepatocellular carcinoma and at determining whether this feature is associated with a definite clinical or pathological characteristic. Expression of c-met was determined by Northern-blot hybridization of a specific probe (human met proto-oncogene) in 18 tumoral and nontumoral liver samples obtained in 18 cirrhotic patients with hepatocellular carcinoma submitted to surgical treatment. Eight of the 18 hepatocellular carcinomas exhibited c-met overexpression, with an increase ranging between 2-fold and 10-fold when compared by densitometry with the surrounding liver. By contrast, in the remaining 10 cases c-met expression was almost identical to that of the surrounding nontumoral liver tissue. Overexpression of c-met was not related to either the age, sex, etiology or functional status of the underlying liver disease, or to the size of the tumor, to its differentiation degree or to the presence of pseudocapsule invasion and existence of additional neoplastic nodules. These data indicate that almost half of the human hepatocellular carcinomas exhibit c-met overexpression. Nevertheless, the biological relevance of this characteristic is not known.
 ...
PMID:c-met mRNA overexpression in human hepatocellular carcinoma. 827 72

The c-met proto-oncogene product is the tyrosine kinase receptor for hepatocyte growth factor. To gain insights into its functions in the liver, we carried out a study of the expression and tyrosine phosphorylation status of the Met protein during hepatic regeneration and in human hepatocellular carcinomas. Following partial hepatectomy of rats, decreased expression of the proreceptor p170MET and reduced levels of tyrosine phosphorylation were seen within 12 h. These changes were still evident 7 days later. By contrast, there was no significant alteration of the Met beta subunit. The analysis of samples from 18 patients with hepatocellular carcinoma revealed that the expression of p160MET proreceptor was increased in non-cancerous areas, while that of the p145 beta MET proreceptor was significantly greater in the tumor tissue than in the non-tumor areas (p < 0.05). These findings suggest that processing of the Met proreceptor is closely associated with regeneration and carcinogenesis of the liver.
 ...
PMID:Analysis of the hepatocyte growth factor receptor in regeneration and oncogenesis of the liver. 870 80

Hepatocellular carcinoma (HCC) is a common type of cancer, with approximately 260,000 new cases each year, and liver cirrhosis is generally considered a major predisposing factor for HCC. However, specific changes of gene expression in liver cirrhosis and HCC remain obscure. The expression of genes for hepatocyte growth factor (HGF), its receptor c-met proto-oncogene, c-myc proto-oncogene, and albumin was analyzed. Gene expression was studied by PCR in seven normal human livers, nine cases of hepatitis C cirrhosis, 12 cases of alcoholic cirrhosis, two cases of liver adenoma, and 12 cases of HCC. HGF and c-met protein were revealed by immunofluorescent staining. HGF mRNA was not expressed in normal livers but was detected in adenomas, in 80% of HCC, and in some cirrhoses. Paraffin-embedded and fresh-frozen tissue samples yielded similar results. Immunohistochemical data correlated with PCR results regarding the overexpression of the HGF/c-met system in HCC. Albumin gene expression was decreased in HCC vs normal livers, consistent with altered function of tumor hepatocytes. The elevated expression of the HGF/c-met system in HCC may play a role in tumor development and/or progression. Tissue localization studies of HGF and its receptor c-met protein support the existence of both autocrine and paracrine mechanisms of action of HGF in HCC vs only a paracrine mechanism in normal liver.
 ...
PMID:Expression of HGF, its receptor c-met, c-myc, and albumin in cirrhotic and neoplastic human liver tissue. 901 Apr 72

The c-met proto-oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), a potent mitogen and motogen for epithelial cells. Because of its profound effects on cell growth and motility, HGF may be important in the development of cancer metastases in hepatocellular carcinoma (HCC). In this study, we examined HGF concentration and expression of the c-met proto-oncogene product (c-Met) in 62 patients with HCC to determine the relationship between the level of expression and clinicopathological features, and patient outcome following hepatectomy. Western blotting was used to examine the c-Met expression, and HGF concentration in tumors was measured using an enzyme-linked immunosorbent assay. c-Met was found to be overexpressed in HCC compared with nontumorous liver tissue (P < .01), and correlated with an increased incidence of intrahepatic metastases (P = .039). Patients were divided into two groups: low c-Met HCC and high c-Met HCC. Patients with high c-Met HCC had a significantly shorter 5-year survival than patients with low c-Met HCC (33.5% vs. 80.3%, respectively; P < .05). However, there was no correlation between HGF concentration in the tumor tissue and clinicopathological factors and patient survival. These results indicate that the expression of c-Met played an important role in tumor growth and metastases in patients who underwent hepatectomy for HCC.
 ...
PMID:Expression of hepatocyte growth factor and its receptor, the c-met proto-oncogene, in hepatocellular carcinoma. 904 8

The c-met proto-oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), a potent mitogen and motogen for epithelial cells. Because of its profound effects on cell growth and motility, HGF may be important in the development of cancer metastases in hepatocellular carcinoma (HCC). In this study, we examined HGF concentration and expression of the c-met-proto-oncogene product (c-met) in 62 patients with HCC to determine the relationship between the level of expression and clinicopathological features, and patient outcome following hepatectomy. Western blotting was used to examine the c-met expression, and HGF concentration in tumors was measured using an enzyme-linked immunosorbent assay. c-met was found to be overexpressed in HCC compared with nontumorous liver tissue (P < .01), and correlated with an increased incidence of intrahepatic metastases (P = .039). Patients were divided into two groups, low c-met HCC and high c-met HCC. Patients with high c-met HCC had a significantly shorter 5-year survival than patients with low c-met HCC (33.5% vs. 80.3%, respectively; P < .05). However, there was no correlation between HGF concentration in the tumor tissue and clinicopathological factors and patient survival. These results indicate that expression of c-met played an important role in tumor growth and metastases in patients who underwent hepatectomy for HCC.
 ...
PMID:Expression of hepatocyte growth factor and its receptor c-met proto-oncogene in hepatocellular carcinoma. 909 89

In the present retrospective study, liver cell dysplasia (LCD) occurring in cirrhotic livers associated or not associated with hepatocellular carcinoma (HCC) was immunohistochemically analyzed for the expression of hepatocyte growth factor receptor (c-met protein), Rb (retinoblastoma gene) protein, E-cadherin, and transforming growth factor-beta-1 (TGF-beta-1). Cytoplasmic c-met protein staining was observed in about half of the HCC's, and its prevalence was about twice as high in high grade vs. low grade tumors, but it was not correlated with proliferative activity as based on PCNA labelling. In LCD, reactivity for c-met protein was restricted to the small cell type. Nuclear staining for Rb protein was found in HCC's, and was not related to type, grade or proliferative activity, whereas no immunoreactivity was observed in normal, hyperplastic or dysplastic hepatocytes. Expression of E-cadherin prevailed in HCC's of lower grade, and particularly in those with a trabecular or acinar growth pattern. E-cadherin staining was detectable in normal and large dysplastic hepatocytes, but not in small dysplastic liver cells. TGF-beta-1 reactivity was observed in more than half the HCC's, but not in normal or dysplastic hepatocytes. These findings underline the phenotypic difference between large cell and small cell liver dysplasia, and support the hypothesis that small cell dysplasia is a precursor lesion in a hepatocarcinogenic pathway.
 ...
PMID:Liver cell dysplasia: reactivities for c-met protein, Rb protein, E-cadherin and transforming growth factor-beta 1 in comparison with hepatocellular carcinoma. 969 Jan 21

The untransformed stable cell line Met murine hepatocytes (MMH), generated from liver explants of transgenic mice expressing a constitutively active truncated form of the human hepatocyte growth factor receptor (cyto-Met), represents an innovative tool for in vitro studies of liver function. In the present report, we show that the MMH-D3 line isolated from the liver of a 3-day-old mouse is a useful model to investigate the regulation of the synthesis and secretion of retinol-binding protein (RBP) by retinol (vitamin A alcohol). Experiments with Northern blot hybridization, metabolic labeling of cellular proteins followed by immunoprecipitation, and Western blot analysis demonstrated that, similarly to the in vivo situation, in MMH-D3 cells the presence of retinol does not affect transcriptional and translational rate of the RBP gene but is essential for regulating the secretion rate of the protein. Unlike HepG2 human hepatocarcinoma cells used thus far in studies of retinoid metabolism, including the synthesis and secretion of RBP, vitamin A deficiency causes, in MMH-D3 cells, the inhibiton of RBP secretion and the protein accumulation in the cell, whereas retinol repletion promptly results in RBP secretion. This model will be very useful in future studies on vitamin A distribution in the organism.
 ...
PMID:MMH cells: An in vitro model for the study of retinol-binding protein secretion regulated by retinol. 1045 50

We have shown that liver myofibroblasts stimulate in vitro invasion of hepatocellular carcinoma cell lines through a hepatocyte growth factor/urokinase-dependent mechanism. Resveratrol, a grapevine-derived polyphenol, has been shown to inhibit cellular events associated with tumor initiation, promotion and progression. The aim of this study was to evaluate the effects of trans-resveratrol on invasion of the human hepatoma cell line HepG2. Cell invasion was assessed using a Boyden chamber assay. Activation of the HGF signal transduction pathways was evaluated by Western blot with phospho-specific antibodies. Urokinase expression was measured by RT-PCR and zymography. Trans-resveratrol decreased hepatocyte growth factor-induced cell scattering and invasion. It also decreased cell proliferation without evidence for cytotoxicity or apoptosis. Trans-resveratrol did not decrease the level of the hepatocyte growth factor receptor c-met and did not impede the hepatocyte growth factor-induced increase in c-met precursor synthesis. Moreover, trans-resveratrol did not decrease hepatocyte growth factor-induced c-met autophosphorylation, or Akt-1 or extracellular-regulated kinases-1 and -2 activation. Finally, it did not decrease urokinase expression and did not block the catalytic activity of urokinase. In conclusion, our results demonstrate that trans-resveratrol decreases hepatocyte growth factor-induced HepG2 cell invasion by an as yet unidentified post-receptor mechanism.
 ...
PMID:Trans-resveratrol, a grapevine-derived polyphenol, blocks hepatocyte growth factor-induced invasion of hepatocellular carcinoma cells. 1140 26

AIM:To study the changes of gene expression of hepatocyte growth factor (HGF) and hepatocyte growth factor receptor (HGFr) in hepatocellular carcinoma (HCC) tissue and nontumorous liver tissue and the relationship between these changes and the biological behavior of the tumor.METHODS:Gene expression of HGF and HGFr in 26 cases of HCC tissue and their adjacent nontumorous liver tissues was determined with digoxigenin labeled DNA probes.RESULTS:Positive expression of HGF in HCC tissue was similar to that in the adjacent nontumorous liver tissue, but positive rate of HGF expression was lower than HGFr gene expression. However, HGFr expression was higher in the metastatic cases than in those without metastasis. It was found that HGFr was overexpressed in HCC tissue as well as in the adjacent nontumorous liver tissue.CONCLUSION:There seems to be a close relationship between overexpression of HGFr gene and tumor metastasis, and the HGF and HGFr system plays an important role in regulating tumor growth and metastasis.
 ...
PMID:Gene expression of hepatocyte growth factor and its receptor in HCC and nontumorous liver tissues. 1181 7

Fibrolamellar variant is an uncommon subcategory of hepatocellular carcinoma with a better prognostic outcome. Proteinases and growth factors that are involved in the remodeling of extracellular matrix may influence the behavior of cancers. To determine whether these factors contribute to the distinct etiologies of fibrolamellar hepatocellular carcinoma and traditional hepatocellular carcinoma, we assayed hepatocyte growth factor, the hepatocyte growth factor receptor, and two hepatocyte growth factor activators, hepatocyte growth factor activator and urokinase-type plasminogen activator, in hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, cirrhotic liver and normal liver. In addition, we examined the urokinase-type plasminogen activator receptor, the type 1 plasminogen activator inhibitor, plasmin, fibrinogen, and the type IV matrix metalloproteinases. Eighteen hepatocellular carcinomas and 11 fibrolamellar hepatocellular carcinomas were obtained as paraffin embedded sections from the University of Pittsburgh Department of Pathology. Frozen tissues from a subset of cases (9 hepatocellular carcinomas, 4 fibrolamellar hepatocellular carcinomas, 12 cirrhotic livers and 2 normal livers) were also available for analysis. Antibodies against urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, hepatocyte growth factor and hepatocyte growth factor receptor were used to analyze immunoperoxidase stained slides from the paraffin blocks. Western blot analyses using antibodies against hepatocyte growth factor, hepatocyte growth factor receptor, phosphotyrosine, hepatocyte growth factor activator, urokinase-type plasminogen activator receptor, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, fibrinogen and plasmin were performed on membrane-enriched fractions from the frozen tissue, as was collagen zymography for matrix metalloproteinase-2 and matrix metalloproteinase-9. The most notable findings are as follows: hepatocyte growth factor activator was only detected in malignant tissue but not cirrhotic liver or normal liver. Although hepatocyte growth factor was detected in most samples, it was significantly elevated in 5/9 hepatocellular carcinomas. Furthermore, 8/9 fibrolamellar hepatocellular carcinomas demonstrated hepatocyte growth factor receptor levels similar to normal, whereas 8/9 hepatocellular carcinomas and 11/12 cirrhotic livers exhibited either an increase or decrease. In contrast, active matrix metalloproteinase-2, which was absent in normal liver, was elevated in fibrolamellar hepatocellular carcinoma as compared to cirrhotic liver and conventional hepatocellular carcinoma. Surprisingly, 10/12 cirrhotic livers and 2/4 fibrolamellar hepatocellular carcinomas but only 1/9 hepatocellular carcinomas were enriched for plasmin. The combined data suggest that the hepatocyte growth factor and plasmin systems tend to be operative in hepatocellular carcinoma and cirrhotic liver, more than fibrolamellar hepatocellular carcinoma. Furthermore, matrix turnover appears to be a more prominent feature of fibrolamellar hepatocellular carcinoma. These findings provide insight into the behavioral differences between hepatocellular carcinoma and the fibrolamellar variant.
 ...
PMID:HGF, MET, and matrix-related proteases in hepatocellular carcinoma, fibrolamellar variant, cirrhotic and normal liver. 1252 8


1 2 3 Next >>