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

The mechanism of resistance to the toxic effects of copper was investigated using a series of copper-resistant hepatoma cell lines maintained in copper-enriched medium. Gel electrophoresis of carboxyamidated cell extracts demonstrated the presence of a pair of low molecular mass cysteine-rich proteins in wild-type and resistant cell lines. These proteins were purified to homogeneity and contained approx. 60% of the total cellular copper. Comparisons of molecular masses, pI values and amino-acid compositions for the purified hepatoma proteins with authentic rat liver metallothionein, as well as cross-reactivity with anti-rat metallothionein antibody, confirmed that the cysteine-rich hepatoma proteins were metallothioneins. The cellular concentration of these hepatoma copper-metallothioneins was proportional to both the level of metal resistance and the amount of copper accumulated by individual cell lines. Further, resistant cells removed from copper-enriched medium for 6-12 months, yet maintaining their level of resistance, showed only a slight decrease in metallothionein concentration. Thus it is proposed that the level of resistance to metal toxicity is mediated by the concentration of copper-metallothionein. It is also suggested that the steady-state level of copper metallothionein is controlled by the degree of metal exposure.
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PMID:Resistance of cultured hepatoma cells to copper toxicity. Purification and characterization of the hepatoma metallothionein. 254 49

It has been pointed out that hepatocellular carcinoma (HCC) develops more frequently in cirrhotic liver with siderosis than in liver without iron deposition, that excess copper in hepatocytes inhibits hepatocarcinogenesis, and that an increase in copper and a decrease in zinc are seen in the sera of patients with various malignant tumors. Iron, copper and zinc concentrations in the serum and liver were estimated in normal subjects and cirrhotic patients with and without HCC. Serum copper level was significantly higher in cirrhotic patients with or without HCC than in normal subjects. No significant differences were observed in the levels of these trace elements in the serum and liver of cirrhotic patients with and without HCC. The current study seems to indicate that iron, copper and zinc do not play an important role in the development of HCC in cirrhotic patients in Japan.
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PMID:Iron, copper and zinc levels in serum and cirrhotic liver of patients with and without hepatocellular carcinoma. 255 Aug 61

The distribution of copper in lysates prepared anaerobically from copper-resistant hepatoma cells radiolabeled with 67Cu was examined in pulse-chase experiments. Initially, the majority of the radioactivity (greater than 85%) coeluted with copper-metallothionein. As the chase time increased there was a gradual loss of 67Cu from metallothionein, with a concomitant increase in the level of 67Cu-labeled glutathione. There was also an increase in 67Cu incorporation into superoxide dismutase. These results suggest that the chelation of copper by metallothionein from a copper-glutathione complex (Freedman, J. H., Ciriolo, M. R., and Peisach, J. (1989) J. Biol. Chem. 264, 5598-5605) is a reversible process. Further, they demonstrate that the copper bound to metallothionein is not permanently sequestered, but can be incorporated into other copper proteins.
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PMID:Intracellular copper transport in cultured hepatoma cells. 255 12

To evaluate the prognostic value of serum copper (S-Cu) and ceruloplasmin and their pathophysiologic significance in human hepatocellular carcinoma (HCC), we studied 49 patients with HCC (20 of which were submitted to partial hepatectomy) compared with 110 patients with liver cirrhosis. In HCC both S-Cu and ceruloplasmin were higher than in cirrhosis; moreover, S-Cu was correlated with the extension of HCC, evaluated by instrumental data and by surgical inspection. In cirrhotic patients, mean S-Cu was 122.9 micrograms/dl (SD, 29.3), in early HCC, 153.0 micrograms/dl (SD, 34.5), and in advanced HCC, 193.1 micrograms/dl (SD, 37.7). Variance analysis gave F = 59.4. In HCC patients S-Cu was positively correlated with ceruloplasmin and with fibrinogen. Survival, evaluated by Mantel's test stratified for surgical therapy, was longer in patients with S-Cu levels lower than 175 micrograms/dl and in those at an earlier stage. We therefore conclude that S-Cu has a relevant diagnostic value in detecting HCC also in early stage and allows prognostic evaluation as regards survival.
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PMID:Serum copper and ceruloplasmin in early and in advanced hepatocellular carcinoma: diagnostic and prognostic relevance. 255 94

Cellular copper metabolism and the mechanism of resistance to copper toxicity were investigated using a wild type hepatoma cell line (HAC) and a copper-resistant cell line (HAC600) that accumulates copper and has a highly elevated level of metallothionein (MT). Of the enzymes involved in reactive oxygen metabolism, only glutathionine peroxidase was elevated (3-4-fold) in resistant cells, suggestive of an increase in the cellular flux of hydrogen peroxide. A majority of the cytoplasmic copper (greater than 60%) was isolated from both cell lines as a GSH complex. Kinetic studies of 67Cu uptake showed that GSH bound 67Cu before the metal was complexed by MT. Depletion of cellular GSH with buthionine sulfoximine inhibited the incorporation of 67Cu into MT by greater than 50%. These results support a model of copper metabolism in which the metal is complexed by GSH soon after entering the cell. The complexed metal is then transferred to MT where it is stored. This study also indicates that resistance to metal toxicity in copper-resistant hepatoma cells is due to increases in both cellular GSH and MT. Furthermore, it is suggested that elevated levels of GSH peroxidase allows cells to more efficiently accommodate an increased cellular hydrogen peroxide flux that may occur as a consequence of elevated levels of cytoplasmic copper.
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PMID:The role of glutathione in copper metabolism and toxicity. 256 91

This paper presents the case report of the coincidental presence of an adenocarcinoma of the rectum and fibrolamellar hepatocellular carcinoma in a 76 year-old man. The tumours were successfully removed by simultaneous resection. The characteristics of hepatocellular carcinoma of the fibrolamellar type are discussed in detail on the basis of the presented case and a survey of the literature. This variant of hepatocellular carcinoma is predominantly found in younger patients. It appears in non-cirrhotic livers and is preferentially localized in the right lobe. Histologically, fibrolamellar hepatocellular carcinoma is characterized by large eosinophilic tumour cells. The cells show trabecular or solid arrangement separated by fibrous septa. Cytoplasmic globules are often found in the tumour cells. In the literature, fibrinogen, CEA, alpha-1-antitrypsin, copper binding protein and copper have been demonstrated in the tumour cells by immunohistochemistry and histochemistry. The fibronectin content is increased in the tumour and seems to correlate with a higher degree of differentiation, as well as a better prognosis. The serum alpha-fetoprotein levels of patients with fibrolamellar carcinomas are normal, in contrast to those in patients with other types of hepatocellular carcinomas. The serum vitamin B12 binding-capacity, as well as neurotensin concentrations are increased. Patients with fibrolamellar carcinomas have a much better prognosis than patients with ordinary hepatocellular carcinomas because of the earlier onset of symptoms, slower tumour progression with late metastasis, and better operability. Two-year survivals of 82% and five-year survivals of 63% have been reported. The prognosis is also better after total hepatectomy followed by liver transplantation.
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PMID:[76-year-old patient with adenocarcinoma of the rectum and fibrolamellar hepatocellular 2d carcinoma. Case report with literature review of hepatocellular carcinoma of the fibrolamellar type]. 282 Jan 56

The classical morphological criteria in the diagnosis of hepatocellular carcinoma (HCC) include: (a) the similarity of tumor cells to hepatic cord cells; (b) the trabecular nature of the growth with capillary and canaliculi formation, and (c) the intravascular growth of trabecular carcinoma. These criteria apply to the most common variants of HCC but they do not suffice in all cases. That makes additional criteria and certain refinements necessary. A promising approach to the diagnosis of HCC is that based upon consideration by the pathologist of some relevant aspects of the natural history of this tumor. A panel of tests exploring the various functions and properties of liver cells should be set up. Tests for bile and fibrinogen synthesis are most important because they reflect specific and exclusive properties of the original cell line. Bile synthesis in tumor tissue is reflected by the finding of cholecholatestasis, namely bilirubinostasis and retention of copper and copper-binding proteins. The positive immunostaining for fibrinogen may appear in the form of cytoplasmic granules occurring in 50% of HCC, or in the form of fibrinogen-ground-glass (G-G) inclusions, representing a specific feature of HCC. During neoplastic transformation oncofetal proteins may reappear, alpha-fetoprotein (AFP) being very common. Despite sensitivity of AFP, this test, similar to alpha-1-antitrypsin (AAT), has very low specificity, because of the widespread occurrence of these proteins in a variety of tumors. The selection of special 'clones' such as Mallory bodies and fibrinogen-G-G is of particular value, because of the specificity of these peculiar cytoplasmic changes. Although rare, the presence of HBV antigens in tumor tissue is virtually pathognomonic for HCC. The availability of nonneoplastic liver tissue for morphological examination is of great help, because it may carry key information or markers of the development stages of HCC: cirrhosis, liver cell dysplasia, HBV antigens, congenital metabolic disorders, such as hemochromatosis and AAT deficiency. The two latter conditions represent the link with the last working hypothesis of the present study, i.e. that during neoplastic transformation hepatocytes may 'switch' their 'phenotype' thus escaping the storage phenomena, which continue to occur in nonneoplastic hepatocytes. This study provides a guideline to a dynamic approach to the diagnosis of HCC. The rationale is listed in 5 points; among them, bile production, fibrinogen synthesis, Mallory body and fibrinogen-G-G selection, HBV antigen expression can be considered at present as confident markers for the morphological diagnosis of HCC.
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PMID:Natural history of hepatocellular carcinoma as viewed by the pathologist. 283 13

Fibrolamellar carcinoma (FLC) of the liver is a clinicopathologic type of hepatocellular carcinoma (HCC) with a favorable prognosis with long-term survival. At variance with the usual HCC, FLC occurs predominantly in young people, both male and female, usually without preexisting liver disease. The distinctive pathologic features of FLC are presented and reviewed. Both gross and microscopic findings suggest that FLC is the malignant counterpart of focal nodular hyperplasia that may arise from preexisting focal nodular hyperplasia. The storage of copper and fibrinogen inside tumor cells is a peculiarity of FLC, and it appears to be in a close relationship with the oncocytic appearance of FLC cells having a deeply eosinophilic, finely granular, mitochondrion-rich cytoplasm. All other immunohistological and ultrastructural findings strongly support the high degree of differentiation of FLC.
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PMID:Fibrolamellar carcinoma of the liver: a distinct entity within the hepatocellular tumors. A review. 283 16

A man of 61 with a 26-year history of progressive cerebellar ataxia was admitted to hospital. He was found to have chronic liver disease and died 22 days after admission. A diagnosis of hepatolenticular degeneration (Wilson's disease) was supported by clinical investigations and confirmed at autopsy, when tissue copper studies were performed. Several unusual features were present, including a unilateral Kayser-Fleischer ring, a hepatocellular carcinoma, peripheral neuropathy, pontine demyelination and calcification of neurones in the medulla. The significance of these findings is discussed with a review of the relevant literature.
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PMID:An unusual case of Wilson's disease. 298 71

In 70 patients with hepatocellular carcinoma without history of antineoplastic chemotherapeutic drugs, anabolic and contraceptive steroids, representative sections of nonneoplastic liver tissue were examined for the presence of etiological markers. Hepatitis B surface antigen-positive hepatocytes were found in 16 (22.8%), alpha-1-antitrypsin globules in 3 (4.2%), Mallory bodies in 9 (12.8%), acicular inclusions in 1 (1.4%), diffuse giant mitochondria in 2 (2.8%), copper-binding protein in 25 (35.7%), greater amount of hemosiderin in 9 (12.8%) cases. Thorotrast was not detected. One or more markers were seen in 38 (54.3%) cases, most frequently in association with liver cell dysplasia and alcoholism. The presence of hepatitis B surface antigen in livers with dysplastic foci was highly significant as compared to organs showing no dysplasia. Only the mentioned antigen and the alpha-1-antitrypsin globules were found to indicate the etiology of the underlying liver lesion. The value of the other markers was found inconsistent in etiological diagnosis.
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PMID:The etiology of underlying liver lesions in 70 autopsied cases of hepatocellular carcinoma. 299 28


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