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 immunostaining patterns of adrenocortical tumors are not clearly defined, primarily due to their inconsistent expression of cytokeratins (CK). To address this issue and to investigate whether adrenocortical tumors can be immunohistochemically differentiated from histologically similar tumors arising from the kidney and liver, we studied four normal adrenal glands, two adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2. Normal adrenal cortical cells showed variable staining with all anti-CK antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs stained with a single anti-CK, although both neoplasms reacted with multiple anti-CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM, but only one tumor stained for CK; frozen sections of this and another, previously negative tumor, however, stained with most of the anti-CK antibodies tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs 18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC immunohistochemically positive on fixed and frozen sections, with CK 19 identified in the ACC that was positive on frozen section alone. All fixed HCCs and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases, respectively), with a proportion of tumors positive for VIM (six and 22 cases, respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28 cases, respectively). The results suggest that CK expression is diminished in most adrenocortical tumors to levels too low to be recognized following the deleterious effects of fixation. While the immunohistochemical absence of CK, EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive, sufficient phenotypic overlap exists such that differentiation between RCC and HCC may not be possible in an individual case.
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PMID:Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and biochemical study with implications for the differential diagnosis of adrenocortical, hepatocellular, and renal cell carcinoma. 137 Dec 62

For an understanding of the molecular basis of the marked decrease in catalase activity of various tumor cells, expression of the catalase gene was studied in rat and human hepatoma cell lines and in rat liver, which was used as a control with high activity. RNA blot hybridization profiles and run-on assays indicated that the decrease in catalase activity was due to depression of catalase gene transcription. Chloramphenicol acetyltransferase (CAT) assays for the fragments with various lengths of the 5'-flanking region (up to -4.5 kb from the ATG codon) of the catalase gene revealed the presence of several cis-acting elements involved in the negative regulation of transcription. The most-upstream element with the strongest activity (-3504 to -3364 bp), when linked to the catalase promoter region (-126 bp) of the CAT construct and subjected to an in vitro transcription assay, did not yield transcripts in experiments with the hepatoma nuclear extract, whereas the unlinked template did yield transcripts. A gel shift competition assay using hepatoma nuclear extract showed the core sequence of the silencer element to be 5'-TGGGGGGAG-3'. A homology search found that the same core sequence was also present in 5'-flanking regions of the albumin gene and of some other liver enzyme genes, the expression of which has been reported to be down regulated in some hepatoma cells. Southwestern (DNA-protein) analysis demonstrated that an approximately 35-kDa nuclear protein bound to the silencer element was present in hepatoma cells but not in rat liver cells.
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PMID:Negative regulation of catalase gene expression in hepatoma cells. 158 55

Metastasis of hepatoma to the brain is a rare event. Even rarer is massive hemorrhage of the brain associated with metastatic hepatoma. A 57-year-old man had cirrhosis of the liver with hepatocellular carcinoma. The tumor spread to the lungs and left occipital lobe of the brain. The primary and secondary neoplasms were negative in detection of mucin, but were immunohistochemically positive to cytokeratin CAM 5.2 and KC; the finding supported the hepatocellular origin of the tumor. The metastatic tumor formed papillae in the lung and produced massive hemorrhage in the left occipital lobe. This case raised the total number of intracranial metastatic hepatic carcinomas to 34 cases. Five of 34 hepatic carcinomas metastatic to brain, including the current one, were hepatocellular carcinoma that produced massive hemorrhage.
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PMID:Massive cerebral hemorrhage from metastatic hepatocellular carcinoma. 166 19

We have previously identified a series of five DNase-I hypersensitive (HS) sites within and around the rat phosphoenolpyruvate carboxykinase (PEPCK) gene. The far upstream region has now been sequenced, and the tissue-specific HS site has been mapped more precisely at 4,800 base pairs upstream of the transcription start site of the PEPCK gene. DNA fragments that include the HS site were cloned upstream of various promoters to test whether these regions modulate transcription of the chloramphenicol acetyltransferase reporter gene. Chloramphenicol acetyltransferase activity was enhanced when the DNA fragment encompassing the upstream HS site was linked to various lengths of the PEPCK promoter or to the heterologous simian virus 40 promoter. This upstream region in conjunction with the proximal promoter, which may contain a tissue-specific element, conferred maximum activation in H4IIE hepatoma cells, which express the endogenous PEPCK gene. When these experiments were performed in XC cells, in which the gene is not expressed, transcriptional activation by the upstream element was still significant. Evidence of a specific protein-DNA interaction, using DNA mobility shift and DNase I footprinting assays, was obtained only when using H4IIE cell nuclear extracts. Competition assay showed that the interacting factor may be similar or identical to the liver-specific factor HNF3. We suggest that this protein factor binds to DNA within the HS site and interacts with the proximal promoter region to control tissue-specific high-level expression of the PEPCK gene.
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PMID:Interaction of a liver-specific factor with an enhancer 4.8 kilobases upstream of the phosphoenolpyruvate carboxykinase gene. 235 22

Human alpha 1-antitrypsin (AAT) is expressed in the liver, and a 318 bp fragment immediately flanking the CAP site of the gene was found to be sufficient to drive the expression of a reporter gene (CAT) specifically in hepatoma cells. The enhancing activity however, was orientation-dependent. The DNA fragment was separated into a distal region and a proximal region. A "core enhancer" sequence GTGGTTTC is present within the distal region and is capable of activity enhancement in both orientations when complemented by the proximal region in the sense orientation. The results strongly suggest that there are multiple cis-acting elements in the human AAT gene that confer cell specificity for its expression. Nuclear proteins prepared from the hepatoma cells bound specifically to the proximal region in a band-shifting assay that was resistant to competition by the globin promoter DNA. Foot-printing analysis showed a protected domain within the proximal region that contains a nearly perfect palindromic sequence TGGTTAATATTCACCA, which may be important in the regulation of AAT expression in the liver.
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PMID:Tissue-specific expression of the human alpha 1-antitrypsin gene is controlled by multiple cis-regulatory elements. 282 29

Alterations in the expression of normal cell surface components on 13 transplantable hepatocellular carcinomas were examined using a heteroantiserum [anti-Mr 105,000 glycoprotein (gp 105)] reactive with a family of nine wheat germ agglutinin binding components from normal rat hepatocytes with an average molecular weight of 105,000. Analysis by two-dimensional polyacrylamide gel electrophoresis of components immunoprecipitated by anti-gp105 antiserum from detergent extracts of transplantable hepatocellular carcinoma cells surface labeled with 125I revealed qualitative and quantitative changes in the expression of anti-gp105-reactive components with the most consistent change being the apparent loss of a pair of acidic (pl 4.1 to 4.3) glycoproteins by all 13 transplantable hepatocellular carcinoma lines. One-dimensional peptide maps of fragments produced following digestion with V8 protease indicated that these acidic components were closely related in structure but differed significantly from other anti-gp105-reactive components. Immunodepletion analysis with monoclonal antibodies and heteroantisera reactive with individual components recognized by anti-gp105 antiserum showed that the two acidic glycoproteins were antigenically and structurally identical to cell-CAM 105, a Mr 105,000 glycoprotein involved in cell-cell adhesion of rat hepatocytes. Antibodies raised against purified cell-CAM 105 were specific in immunoprecipitation assays for the acidic components, strongly inhibited reaggregation of hepatocytes, and displayed no reactivity by indirect immunofluorescence or immunoprecipitation analysis with transplantable hepatocellular carcinoma cells. These results suggest that major alterations in the expression of cell-CAM 105 may be a consistent feature of the malignant phenotype.
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PMID:Alterations in the expression of a hepatocyte cell adhesion molecule by transplantable rat hepatocellular carcinomas. 299 Jun 76

Chloramphenicol in a dose of 50-200 micrograms/ml sharply inhibits the incorporation of 14C-labelled amino acids into proteins of ascites Zajdela hepatoma cells while it has no effect on protein biosynthesis in rat liver cells. In vivo chloramphenicol selectively inhibits this process in ascites tumour cells of rat Zajdela hepatoma and mouse Ehrlich carcinoma and hepatoma 22a, without inhibiting the process in various organs of tumour-bearing animals. The inhibition of labelled amino acid incorporation into nuclear and especially nuclear matrix proteins is more pronounced than into the whole tissue. A certain degree of inhibition was revealed in liver cells as well.
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PMID:[Selective inhibition by chloramphenicol of protein biosynthesis in ascites tumor cells]. 649 49

A newly synthesized mycophenolic acid (MPA) derivative, ethyl O-[N-(p-carboxyphenyl)-carbamoyl]-mycophenolate (CAM, NSC-297879D) was tested for antitumor activity, when given orally, against transplantable murine tumors. The compound was markedly effective against transplantable murine tumors. The compound was markedly effective against leukemia P388 and L1210, lymphoma L5178Y, mastocytoma P815 and sarcoma Meth-A, moderately effective against sarcoma-180, C3MC2 and BAMC1, Ehrlich carcinoma, Lewis lung carcinoma and melanoma B16 and marginally effective against hepatoma MH134. The antitumor effects were manifested not only in growth inhibitory effects on subcutaneously transplanted tumors but also in the prolongation of life span of mice int which the tumors had been inoculated intraperitoneally or subcutaneously. The growth of primary transplants of a mammary tumor which developed spontaneously in a C3H/He mouse was inhibited by consecutive administration of CAM frm the 34th day after the transplantation. Oral CAM was more potent than its mother compound, MPA, in the tumor models examined. These results indicate that orally administered CAM has a wide antitumor spectrum.
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PMID:Antitumor activity of a new compound, ethyl O-[N-(p-carboxyphenyl)-carbamoyl]-mycophenolate, against various experimental tumors upon oral administration. 727 50

Hemopexin (Hx) is induced during the acute phase response (APR) by the cytokine interleukin (IL)-6. A type II IL-6 response element (RE) of the Hx gene has been characterized recently (J. Biol. Chem. (1994); 269, 12654-12661). To assess Hx gene regulation by other agents, various cytokines and growth factors were tested for their ability to induce Hx in rat hepatoma H-35 cells. IL-6-type cytokines, IL-1 beta and TNF-alpha, in contrast to transforming growth factor-beta (TGF-beta), hepatocyte growth factor and insulin significantly increased Hx gene expression. Chloramphenicol acetyltransferase (CAT) activity in H-35 cells transfected with constructs that contained the 5'-flanking Hx promoter region or multiple copies of the Hx IL-6-RE fused to the CAT gene was upregulated only by IL-6-type cytokines, although to varying degrees. These data indicate that signal transduction pathways mediated by IL-6-type cytokines but not those by IL-1 beta and TNF-alpha converge on the common Hx IL-6-RE.
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PMID:The type II hemopexin interleukin-6 response element predominates the transcriptional regulation of the hemopexin acute phase responsiveness. 785 66

Previous studies have shown that in vitro expression of the neural cell adhesion molecule (N-CAM) can be regulated by the products of homeobox genes HoxB9, -B8, and -C6. N-CAM is a Ca(2+)-independent immunoglobulin-related CAM that plays an important role in neural development. In the present study, we investigated whether the liver cell adhesion molecule (L-CAM) a member of the Ca(2+)-dependent CAM family (cadherins) is also regulated by homeobox-containing genes. In transient cotransfection experiments of NIH 3T3 cells, we observed that both HoxD9 and liver-enriched POU-homeodomain transcription factor, HNF-1, activated chloramphenicol acetyltransferase gene reporter constructs containing the L-CAM promoter and an enhancer present in the second intron of the chicken L-CAM gene. Using electrophoretic mobility-shift assays, we found that components of cell extracts from NIH 3T3 cells transfected with HoxD9 bound to a small region of the L-CAM enhancer having a consensus sequence that is a putative binding site for HNF-1. Components of extracts from the chicken hepatoma cell line LMH that had been transfected with an HNF-1 expression vector also bound to this same site. In nuclear run-on experiments with nuclei from LMH cells that were transfected with expression vectors for HoxD9 or HNF-1, L-CAM RNA levels were increased 33-fold and 4-fold respectively. Using the same run-on procedure, it was confirmed that nuclei prepared from normal embryonic chicken liver cells expressed the RNAs for HoxD9, HNF-1, and L-CAM. Taken together with previous observations, these data raise the possibility that homeobox-containing genes will have a widespread role in the place-dependent expression of CAMs belonging both to immunoglobulin-related and to cadherin families.
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PMID:Regulation in vitro of an L-CAM enhancer by homeobox genes HoxD9 and HNF-1. 791 99


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