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)

Superoxide dismutase (SOD) activity in hepatocellular carcinoma (HCC) tissue was studied. It was observed that activities of total SOD, Cu, Zn-SOD and Mn-SOD in HCC tissue were lower than those in normal liver tissues respectively (P less than 0.001 & 0.01 less than P less than 0.05). SOD activity in poorly differentiated HCC tissue was lower than that in well differentiated HCC tissue. Contents of copper, zinc and manganese in HCC tissues were lower than those in normal liver tissues respectively (P less than 0.001 & P less than 0.01). This study suggests that decreased content of copper, zinc and manganese may be one of the factors that lead to impairment of SOD activity. The characteristic of lower SOD activity in HCC tissue and poorly differentiated HCC tissue may be a negative regulation to limitless proliferation and poor differentiation of liver cancer cells.
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PMID:[Superoxide dismutase activity in tissues from 19 cases of hepatocellular carcinoma]. 216 38

Three nuclear factors, the Ah receptor, XF1, and XF2, bind sequence specifically to the Ah response elements or xenobiotic response elements (XREs) of the cytochrome P450IA1 (P450c) gene. The interactions of these factors with the Ah response element XRE1 were compared by three independent methods, methylation interference footprinting, orthophenanthroline-Cu+ footprinting, and mobility shift competition experiments, using a series of synthetic oligonucleotides with systematic alterations in the XRE core sequence. These studies established the following (i) all three factors interact sequence specifically with the core sequence of XRE1; (ii) the pattern of contacts made with this sequence by the Ah receptor are different from those made by XF1 and XF2; and (iii) although XF1 and XF2 can be distinguished by the mobility shift assay, the sequence specificities of their interactions with XRE1 are indistinguishable. Further characterization revealed the following additional differences among these three factors: (i) XF1 and XF2 could be extracted from nuclei under conditions quite different from those required for extraction of the Ah receptor; (ii) XF1 and XF2 were present in the nuclei of untreated cells and did not respond to polycyclic compounds, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and beta-napthoflavone, while nuclear Ah receptor was undetectable in untreated cells and rapidly increased in response to TCDD; (iii) inhibition of protein synthesis did not affect the TCDD-induced appearance of the Ah receptor but substantially decreased the constitutive activities of XF1 and XF2, suggesting that the Ah receptor must be present in untreated cells in an inactive form that can be rapidly activated by polycyclic compounds, while the constitutive expression of XF1 and XF2 depends on the continued synthesis of a relatively unstable protein; (iv) the receptor-deficient and nuclear translocation-defective mutants of the hepatoma cell line Hepa1, which are known to lack nuclear Ah receptor, expressed normal levels of XF1 and XF2, suggesting that the former factor is genetically distinct from the latter two; and (v) a divalent metal ion, probably Zn2+, is known to be an essential cofactor for the Ah receptor but was not required for the DNA-binding activities of XF1 and XF2. Together, these findings indicate that the Ah receptor is distinct from XF1 and XF2, while the latter two activities may be related. Because the DNA-binding domains of these three factors overlap substantially, their binding to XREs is probably mutually exclusive, which suggests that the interplay of these factors at Ah response elements may be important to the regulation of CYP1A1 gene transcription. The results of preliminary transfection experiments with constructs harboring XREs upstream of the chloramphenicol acetyltransferase gene driven by a minimal simian virus 40 promoter are presented that are consistent with this hypothesis.
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PMID:Multiple DNA-binding factors interact with overlapping specificities at the aryl hydrocarbon response element of the cytochrome P450IA1 gene. 217 7

The in vitro interaction of mercury, copper (II) and cadmium with human glutathione transferase (GST) pi was studied using reduced glutathione (GSH) and 1-chloro-2,4-dinitrobenzene as substrate. Tumor specific human GST pi was isolated from the human hepatoma derived PLC/PRF/5 cell line. The inhibition of the GST pi activity was dose dependent. Kinetic studies never revealed competitive inhibition. A parabolic inhibition was found with GSH as the variable substrate. The heavy metals are spontaneously conjugated with GSH and cysteine, but interact with GST pi by direct binding to this protein. This binding could have a protective function against heavy metals.
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PMID:In vitro interaction of mercury, copper (II) and cadmium with human glutathione transferase pi. 221 73

This study demonstrates the unique clinical and histologic aspects of fibrolamellar hepatic carcinoma, a rare variant of hepatocellular carcinoma. Three cases are reviewed and an extensive study of immunologic and intracellular substances defining this tumor is presented. Length of survival was considerably longer than typical hepatoma. The cause of death generally is due to a lack of control of the primary tumor. Successful treatment appears to relate to the ability to perform a total excision of the primary hepatic tumor. Chemotherapy should be used only in the presence of metastatic disease. Surgical resection of metastatic disease, unlike the usual hepatocarcinoma, may have some beneficial use. Fibrinogen was found in all tumors. It is possible that this tumor produces fibrinogen to create its unique histologic appearance. Carcinoembryonic antigen is described for the first time in this tumor. Both deposits of alpha-1 antitrypsin and copper were found in most of the tissues studied. The presence and amounts of these substances differ markedly from the common type of hepatoma. This unique composition of intracellular components may both facilitate histologic diagnosis, particularly if the amount of tissue is limited, and give further insight into the etiology of this tumor.
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PMID:Fibrolamellar carcinoma of the liver. Review of three cases and the presentation of a characteristic set of tumor markers defining this tumor. 240 35

Effects of o-phenanthroline, 2,2'-dipyridyl and neocuproine, which form stable complexes preferentially with Fe(II), Fe(II) and specifically with Cu(I), respectively, on the inhibitory activity of bleomycin against DNA synthesis of rat ascites hepatoma AH66 cells were examined. The inhibitory activity of metal-free bleomycin was suppressed in the presence of o-phenanthroline or 2,2'-dipyridyl, but not by neocuproine, though these chelating agents also showed the inhibitory activity against the DNA synthesis of the cells by themselves alone. The activity of bleomycin-Cu(II) was also suppressed by o-phenanthroline, but bleomycin-Fe(II) and bleomycin-Fe(III) exhibited some activities in the presence of o-phenanthroline. The growth inhibitory activity of bleomycin against HeLa cells was also suppressed by o-phenanthroline. From these results, bleomycin-iron complexes were suggested to be responsible to the bleomycin action in cells.
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PMID:Effects of o-phenanthroline, 2,2'-dipyridyl and neocuproine on the activities of bleomycin to inhibit DNA synthesis and growth of cultured cells. 243 Sep 25

The human metallothioneins are represented by a multigene family consisting of about 14 members. A number of MT-like genes have been isolated from a human genomic library and in this report, four MT genes have been characterized. Our results show that two of these genes represent the MT-I and MT-II processed genes. The other two genes (MT-IF and MT-IG) are functional members of the MT-I gene family. The amino acid sequence encoded by the MT-IF and MT-IG genes differ from the amino acid sequences of the published MT-I proteins at few positions. The 5'-flanking region of these genes contain metal responsive elements. Our studies show that the MT-IF and MT-IG genes are differentially regulated in two human hepatoma cell lines, HepG2 and Hep3B2, and a human lymphoblastoid cell line, WI-L2 in response to the heavy metals cadmium, zinc and copper, and glucocorticoids. In addition, these genes also show cell-type specific expression.
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PMID:Structure and expression of the human metallothionein genes. 244 57

The rainbow trout hepatoma (RTH) cell line responds to heavy metals such as zinc and cadmium by synthesizing the ubiquitous thiol-rich protein metallothionein (MT). From this cell line we have isolated two full-length cDNA clones, tMT-A and tMT-B, which encode two similar but distinct trout MTs. The clones were isolated by cross-homologies between the trout MT mRNAs and a human MT riboprobe. Clones tMT-A and tMT-B code for proteins of 61 and 60 amino acids, respectively; the one extra amino acid in tMT-A is due to an apparent insertion at position 31 of the protein. There are also two other amino acid changes between the two isoforms. Overall, the coding regions show extensive homologies to mammalian MTs, especially at the cysteine residues and at a core sequence at the boundary of the two domains. However, closer examination reveals a number of significant differences in positions usually invariant in the mammalian MTs. Northern blot analysis of RNA from metal-treated RTH cells demonstrated MT-mRNA is induced to high levels by zinc, low levels by cadmium, and minimally by copper. In contrast, intraperitoneal injections of rainbow trout demonstrated that all three metals induce MT-mRNA to comparable levels in the liver. Southern blot analysis of trout DNA cleaved with three restriction enzymes suggests that the trout family of MT genes is probably limited to these two members.
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PMID:The rainbow trout metallothioneins: molecular cloning and characterization of two distinct cDNA sequences. 244 99

A liver cell carcinoma removed surgically by partial hepatectomy from a 79-year-old woman contained abundant orcein-positive granules in many tumour cells. The granules were similar to those usually identified as representing copper-associated protein, yet they lacked copper, as demonstrated by negative rhodanine and rubeanic acid stains and energy dispersive X-ray microanalysis.
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PMID:Liver cell carcinoma with orcein-positive granules and no identifiable copper. 277 21

We have examined the effect of heavy metals on the expression of two major groups of stress-induced proteins in fish cell lines: the 70 kDa heat-shock proteins (hsp70) and metallothioneins (MTs). The rainbow trout hepatoma (RTH) cell line synthesized the hsp70 protein in response to zinc and heat shock, while chinook salmon embryonic (CHSE) cells synthesized this protein in response to these inducers, as well as cadmium. The synthesis of this 70 kDa protein was correlated with the accumulation of hsp70 mRNA as measured by hybridization to a trout hsp70 gene probe. Heavy metals also induced the synthesis of MT in RTH cells. However, heat shock did not result in induction of MT and its mRNA. Unlike RTH cells, CHSE cells did not synthesize MT following exposure to cadmium or zinc. When these cells were treated with 5-azacytidine prior to heavy metal treatment, accumulation of MT mRNA was observed. Northern blot analysis of total RNA from 5-azacytidine treated CHSE cells, using a trout MT (tMT-B) cDNA probe, indicated that the time-course of induction and the maximal level of MT mRNA accumulation in response to cadmium and zinc paralleled that observed in RTH cells. Copper and dexamethasone were ineffective in inducing MT mRNA in 5-azacytidine-treated CHSE cells. These results indicate that MT is specifically induced in response to heavy metal treatment, whereas the synthesis of hsp70 appears to be a general stress response. Furthermore, MT is differentially regulated by heavy metals and dexamethasone in these cell lines and the expression of MT is cell-type-specific.
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PMID:Analysis of stress-induced gene expression in fish cell lines exposed to heavy meals and heat shock. 246 89

A 33-year-old man with Wilson's disease developed hemoptysis and radiographic evidence of nodular pulmonary infiltrates. A premortem diagnosis of hepatocellular carcinoma was made on the basis of alpha-naphthylannidase stains of pulmonary tissue obtained by open lung biopsy. We review all previous cases of Wilson's disease with this unusual complication and discuss the role of copper in hepatic oncogenesis as well as the alpha-naphthylannidase stain for the diagnosis of hepatocellular carcinoma.
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PMID:Hepatocellular carcinoma in Wilson's disease. Case report and review of the literature. 247 36


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