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)

Minute hepatomas with prominent copper accumulations were resected in two women, aged 60 and 62 years, who had never suffered from jaundice. Mild elevation of serum alpha-fetoprotein level was found in both patients. One tumor was diagnosed by celiac angiography, and the other was determined by an ultrasonic echogram. Microscopically, these two tumors were relatively well-differentiated hepatocellular carcinoma, though having less-differentiated foci. Many cancer cells contained numerous copper granules stained by orcein, Victoria blue, and p-dimethylaminobenzylidene rhodanine. Ultrastructurally, cancer cells contained many secondary lysosomes with an electron-dense material. We concluded that the excessive copper in the cancer cells was aggregated lysosomal copper metallothionein, and that it might not be carcinogenic but stored by an altered metabolism of copper and copper-binding proteins with the neoplastic transformation.
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PMID:Minute hepatoma with excessive copper accumulation. Report of two cases with resection. 300 75

A patient is described with micronodular cirrhosis, partial (heterozygous, MZ) deficiency of alpha-1-antitrypsin (AAT) and hepatocellular carcinoma. The patient did not drink alcohol and all serological markers of infection with hepatitis B virus were absent. Death was due to intra-peritoneal bleeding from a multifocal liver tumour. Histology revealed multiple intracytoplasmic AAT globules in hepatocytes at the periphery of the cirrhotic nodules. Copper granules, present in the same non-neoplastic liver cells may have resulted from minor cholestasis. Within the neoplastic hepatocytes AAT globules were sparse and copper deposits co-existed with the globular variant of Mallory bodies. The case is presented in support of the postulated association of partial deficiency of AAT, chronic liver disease and hepatic neoplasia.
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PMID:Cirrhosis and hepatocellular carcinoma in a patient with heterozygous (MZ) alpha-1-antitrypsin deficiency. 300 53

Unlike hepatocellular hepatoma (HCC), the so-called fibrolamellar hepatoma (FLH) is found almost exclusively in the non-cirrhotic, non-infected liver. Patient characteristics and the course of the disease in FLH differ markedly from HCC. FLH represents only a small portion of hepatomas in general (approx. 2%), but accounts for over 40% of hepatomas in young adults. We present the case of a 38-year-old woman showing the typical histological findings of polygonal eosinophilic tumor cells and characteristic lamellar bundles of fibrous stroma, which led to the diagnosis of FLH. The approx. 140 cases of FLH published in the world literature are also presented and discussed. The usefulness of additional examinations (neurotensin, vitamin B12 binding capacity and copper stains) is mentioned. The difficulty in diagnosing FLH lies in its histological differentiation from focal nodular hyperplasia. When diagnosed early, however, FLH is characterized by good resectability with a chance of cure or at least a markedly better survival rate than HCC.
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PMID:[Fibrolamellar hepatoma]. 302 Jun 85

The presence of copper and copper-binding protein (CBP) within tumor cells was searched by histochemical methods (rhodanine, rubeanic acid and Shikata's orcein) in a group of 39 autopsies, all consecutive cases of hepatocellular carcinoma (HCC) associated with cirrhosis (HCC + C). In 2 cases, fibrolamellar carcinoma (FLC) not associated with cirrhosis was observed at surgery. Considerable amounts of copper and CBP were found within tumor cells only in the 2 FLC cases and in 1 HCC + C case, in a portion of the tumor showing FLC-like features. Copper-positive tumor cells had an oncocytic appearance, which was confirmed by ultrastructural examination. In 64% of the HCC + C cases (25 out of 39), copper and CBP deposits were found in nonneoplastic hepatocytes mainly distributed along the periphery of cirrhotic nodules. The present study indicates that the storage of copper inside tumor cells is a peculiarity of the FLC type of HCC with a close relationship to the oncocytic nature of neoplastic hepatocytes. The significance of copper deposits in nonneoplastic cirrhotic hepatocytes remains a matter for further investigations.
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PMID:Copper and hepatocellular carcinoma. 302 52

We describe a human genomic clone containing the metallothionein (MT) IF and MT IG genes. Southern blot analysis and partial DNA sequence determinations show that these genes are organized in a head-to-head fashion and are located approximately 7.0 kilobases apart from each other. Sequence analysis shows that the MT IF gene contains three exons separated by two introns. All of the intron-exon junctions are defined by the GT-AG rule. The 5' flanking region shows the presence of a duplicated metal regulatory element (TGCGC CCGGCCC) important in heavy-metal induction of this gene and a sequence for its basal level expression (GCGGGGCGGGTGCAAAG). The 5' flanking region is also highly G + C rich (approximately 75%) and contains several GC boxes (GGGCGG), probably important in the binding of transcription factors. The TATAA box and the AATAAA sequence are represented by their variants, the TATCAA box and the AATTAA sequence, respectively. This gene is functional and inducible by heavy metals but not by dexamethasone in mouse LMTK- cells after its transfer on a plasmid containing the herpes simplex virus thymidine kinase gene. Further studies on various human cell lines show that this gene is not expressed in a splenic lymphoblastoid cell line (WI-L2) but is expressed in two hepatoma cell lines (Hep 3B2 and Hep G2) in response to cadmium, zinc, and copper. Dexamethasone appears to have no significant effect on its expression. The studies suggest that the MT IF gene shows cell-type-specific expression and is differentially regulated by heavy metals and glucocorticoids.
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PMID:Structure, organization, and regulation of human metallothionein IF gene: differential and cell-type-specific expression in response to heavy metals and glucocorticoids. 302 27

Tissue copper contents in 38 primary and 45 metastatic hepatic malignancies and 15 control livers were analyzed by atomic absorption spectrophotometry. The average copper content of 15 control livers was 23.1 +/- 13.0 micrograms/g dry weight (microgram/gdw). The copper content of five cholangiocellular carcinomas (CCCs) and 45 metastatic cancers was almost equal to the control level. Thirty three hepatocellular carcinomas (HCCs) contained a larger amount of copper (61.5 +/- 76.8 micrograms/gdw) than the control livers (p less than 0.05), but the copper content of HCCs showed a considerably wide variation. The average copper content of nine minute HCCs (126 +/- 112 micrograms/gdw) was significantly (p less than 0.05) higher than that of 24 large HCCs (37.2 +/- 39.9 micrograms/gdw). Histologically, orcein and paramethylaminobenzylidene rhodamine positive granules were seen in eight and four of nine minute HCCs, respectively. These granules were also found in some large HCCs, but were never found in CCCs and metastatic cancers. It was concluded that these excessive accumulations of copper and copper-binding proteins might present a helpful finding to distinguish some cases of HCC, especially small HCC, from CCCs, metastatic cancers and hypertrophic regenerative nodules of cirrhotic livers. The significance and possible pathogenesis of these copper accumulations in HCCs require further studies.
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PMID:Tissue copper content in primary and metastatic liver cancers. 303 46

The human metallothionein (MT)-IG gene (hMT-IG) is tandemly linked in a head-to-head fashion with the hMT-IF gene. The hMT-IG gene encodes a MT-I polypeptide and has a tripartite structure. The 5'-flanking region of the hMT-IG gene has a TATAA box, four GC motifs, and at least four metal responsive elements. The 3'-untranslated region has a variation of the polyadenylation signal, AATTAA, and the 3'-flanking region a YGTGTTYY RNA processing signal. This gene is expressed in hepatoma-derived cell lines (Hep G2 and Hep3B2) in response to the heavy metals (cadmium, copper, and zinc) but not to the glucocorticoid analogue dexamethasone. In contrast, the lymphoblastoid cell line (Wi-L2) does not express the hMT-IG gene. These results suggest that the hMT-IG gene is regulated differentially and in a cell type-specific manner. Transient expression studies of the chloramphenicol acetyltransferase (CAT) gene under the transcriptional control of either the hMT-IG or hMT-IF promoter in Hep G2 cells has demonstrated that both promoters contain all the necessary cis-acting elements to elicit a similar pattern of heavy metal inducibility. However, the hMT-IG promoter in all instances is five times more active than the hMT-IF promoter. The differences in promoter activity of these genes could possibly be due to inherent differences in their basal level regulatory sequences. The expression of MT-IGcat in transfected Wi-L2 cells demonstrates that the hMT-IG promoter is not cell type-specific.
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PMID:Structure and expression of the human metallothionein-IG gene. Differential promoter activity of two linked metallothionein-I genes in response to heavy metals. 340 43

A series of four cell lines resistant to the toxic effect of copper were developed from Morris rat hepatoma cells by gradually increasing the concentration of copper in the growth medium. The EC50, that concentration of copper that kills and/or inhibits the growth of 50% of the cells after 72 h, increased 4-fold over that for wild type cells in the most resistant cell line. These cells were also resistant to zinc, cadmium, and mercury toxicity, but not to nickel or cobalt. The amount of copper in the soluble protein pool of the resistant cells increased proportionally with the concentration of copper in the medium in which they were maintained. Associated with copper accumulation was the production of an 18-kDa cysteine-rich protein which complexes a significant amount of the metal. It is suggested that resistance to copper toxicity is due to sequestration of the metal by this protein. When resistant cells were removed from the copper-enriched environment, cellular copper levels rapidly fell to that observed for wild type cells, but no reduction in either the EC50 or the level of the cysteine-rich protein was noted. This suggests that a permanent change responsible for copper resistance had occurred which is maintained in the absence of the metal.
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PMID:Resistance to copper toxicity of cultured hepatoma cells. Characterization of resistant cell lines. 374 69

The clinical features and investigations of 17 patients were analysed. Thirteen of them were Chinese and the rest Indians. Their ages at presentation ranged from 8 to 63 years (mean 18.35 years). Thirteen patients (76%) were symptomatic; 8 with predominantly hepatic manifestations and 5 with neurological features. Four were asymptomatic siblings. At diagnosis, however, 10(59%) had features of liver involvement singly, 3 (18%) had neurological involvement alone and 4 (27%) had mixed presentations. Family histories were available in 15 patients; 26.9% of siblings had Wilson's Disease. Serum ceruloplasmin was low in 82% of the patients. 24-hour urinary copper was measured in 16 patients and was raised in all of them. About half the patients (41%) had evidence of concomittant renal tubular dysfunction with hypouricaemia and aminoaciduria. Three patients (18%) had joint involvement at presentation. All 17 patients were treated with Penicillamine. Complications due to therapy included pemphigus in one and toxic epidermal necrolysis and later a lupus like syndrome in another. The features of clinical improvement included fading of K-F rings, improvement of neurological signs and the normalisation of serum transaminases. One patient developed primary hepatocellular carcinoma 5 years after presentation. Delay in diagnosis was encountered in half of the patients reviewed. Being a treatable condition, Wilson's Disease, although rare, should always be thought of in patients with haemolysis, liver diseases or extrapyramidal disorders.
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PMID:Wilson's disease revisited in the tropics. 375 94

There was no direct inhibition of DNA synthesis in ascites hepatoma 22A cells after intraperitoneal injection of single doses of copper (II) complexes with amino acids into tumor-bearing C3HA mice. Meanwhile cis-dichlorodiamine platinum (II) (DDP) as well as sarcolysine showed such inhibition. Copper (II) complexes with alpha-amino acids displayed as significant superoxide dismutase-like activity at concentrations corresponding to therapeutic doses of these compounds. The complexes of copper (II) combined with DDP give an additive antitumor effect in solid tumors of mice.
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PMID:[Characteristics of the mechanism of action of complex copper (II) compounds with alpha-amino acids]. 403 65


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