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)

In recent studies we have identified PC2 and PC3, members of a family of serine proteases that are related structurally to subtilisin, and have provided evidence that these are involved in the tissue-specific processing of prohormones and neuropeptides. PC2 is expressed at high levels in the islets of Langerhans, where it participates in the processing of proinsulin to insulin (S.P.S. and D.F.S., unpublished data). To evaluate the regulated expression of the human PC2 (hPC2) gene we have analyzed its structure and characterized its promoter. A map of the gene was constructed by using 11 clones isolated from two human genomic DNA libraries. The gene spans greater than 130 kilobase pairs and consists of 12 exons. Comparison with the structure of the gene encoding human furin, another member of this superfamily, revealed a high degree of conservation of exon-intron junctions. The hPC2 gene was localized to chromosome 20, band p11.2. The 5' flanking region of the hPC2 gene is very G+C-rich and contains six potential Sp1 binding sites but no TATA or CAAT box. Expression of chloramphenicol acetyltransferase reporter fusions containing the putative promoter region was observed to occur in beta TC-3 mouse insulinoma cells but not in HepG2 human hepatoma cells, consistent with the known tissue-specific pattern of expression of the hPC2 gene. Analysis of the level of chloramphenicol acetyltransferase activity with several deletion mutants identified the region from -1100 to -539 from the translation start site as essential for hPC2 promoter activity.
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PMID:Identification and analysis of the gene encoding human PC2, a prohormone convertase expressed in neuroendocrine tissues. 159 2

The retinoblastoma gene (Rb) is one of the tumor suppressor genes to have already been cloned. Deletions and inactivations of the gene have been widely observed in various types of human tumor. To study the generality of Rb alteration in human tumors, 121 cases of tumor DNAs were examined for abnormalities in the gene structure by blot hybridization. Deletions of both alleles were detected in hepatocellular carcinoma, insulinoma and neuroblastoma. Rearrangements and allelic deletions of the Rb gene were, moreover, observed in some brain tumors and hepatocellular carcinomas, respectively. All were surgically resected tumors. The observations suggest the inactivation of Rb through structural alterations sometimes to correlated with the development or progression of these types of human tumor.
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PMID:Deletions and rearrangements of the retinoblastoma gene in hepatocellular carcinoma, insulinoma and some neurogenic tumors as found in a study of 121 tumors. 166 38

Since porcine islets are considered a likely tissue source for islet transplantation we have studied the insulin secretory responses to stimuli and some of the cell surface antigen characteristics of porcine islet cells. In a static incubation system, the threshold level of glucose required for the stimulation of insulin secretion from freshly isolated porcine islets was found to be between 2.8 and 4.2 mmol glucose/l. Arginine (5 mmol/l) and 3-isobutyl-l-methylxanthine (1 mmol/l) potentiated insulin release induced by 8.3 mmol glucose/l. Leucine (5 mmol/l) initiated release in the presence of 2 mmol glucose/l. Neither beta-hydroxybutyrate (10 mmol/l) nor octanoate (5 mmol/l) potentiated insulin release induced by 8.3 mmol glucose/l, but beta-hydroxybutyrate initiated release in the presence of 2 mmol glucose/l while octanoate did not. A 125I-labelled protein A binding assay and an enzyme-linked immunosorbent assay system were used to detect antibody binding to islet and non-islet cells. Monoclonal antibodies raised against intact rat islets were shown to bind to both porcine and rat islet cells but not to rat hepatoma tissue culture cells or rat insulinoma cells. The serum from recently diagnosed type I diabetics was shown to bind to rat islet cells in a 125I-labelled protein A binding assay, while serum from control subjects showed little, if any, binding. Porcine islet cells were unable to distinguish between the sera of recently diagnosed type I diabetics and controls in a similar assay. In conclusion, porcine islets respond to many of the major insulin secretagogues to which human islets are sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunological and insulin secretory studies on isolated porcine islets of Langerhans. 169 4

The following publication describes the diagnostic approach in different benign and malignant space-occupying lesions of the liver and pancreas. An essential prerequisite is that all imaging methods are actually available and can be made use of. While taking the cost factor into consideration, flow diagrams are worked out for haemangiomas, focal nodular hyperplasia, hepatocellular carcinoma and liver metastases, as well as for carcinoma of the pancreas and for insulinoma.
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PMID:[X-ray diagnostic strategies in liver and pancreatic tumors]. 255 64

We previously found that patients with hypoglycemia due to chronic renal and liver disease had anomalous metabolic responses to glucose and glucagon stimulation. In this study we evaluated the use of glucagon (2 mg, iv) tests in the diagnosis of spontaneous hypoglycemia secondary to hepatocellular carcinoma (HCC) and insulinoma. Twenty-one normal subjects, 45 patients with HCC (11 with hypoglycemia), and 14 patients with insulinoma (all with hypoglycemia) were studied. The fasting blood glucose level was low in all patients with hypoglycemia. The fasting plasma insulin and C-peptide concentrations were high in patients with insulinoma and low in patients with HCC and hypoglycemia. The blood glucose responses to glucagon administration were less than normal in patients with HCC and hypoglycemia and within normal limits in patients with insulinoma. The insulinoma patients had increased plasma insulin and C-peptide responses to glucagon despite having low blood glucose levels. Compared with the HCC patients without hypoglycemia, HCC patients with hypoglycemia had impaired plasma insulin and C-peptide responses. The fasting hypoglycemia, hypoinsulinemia, and impaired insulin/C-peptide responses to glucagon in patients with hepatoma and hypoglycemia presumably reflect the production of insulin-like substances by the hepatoma. We conclude that glucagon administration results in characteristic responses in these groups of patients and can be of use in the diagnosis of spontaneous hypoglycemia secondary to hepatoma or insulinoma.
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PMID:The use of glucagon challenge tests in the diagnostic evaluation of hypoglycemia due to hepatoma and insulinoma. 284 61

Transgenic mice carry cloned DNA fragments that have been introduced into the mouse genome, generally by microinjection into pronuclei. They can be used to determine the cis-acting DNA elements responsible for the tissue-specific expression of genes. For this purpose, transgenic mice were obtained carrying either the mouse albumin gene or the human insulin gene. In the first instance, it was shown that the regulatory sequences necessary for expression of the albumin gene transfected into differentiated hepatoma cells are not sufficient to induce its expression in transgenic mice. In contrast with the albumin gene, the short sequence upstream to the insulin gene necessary for its expression in transfected insulinoma cells is sufficient to allow expression in transgenic mice. Similar experiments were performed to study another crucial step in differentiation of lymphoid B cells, namely rearrangement of the immunoglobulin (Ig) genes. The chicken Ig lambda light chain gene in the germ line (unrearranged) form was introduced into the mouse genome, and the rearrangement observed in transgenic mouse lines is briefly described.
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PMID:Transgenic mice: a tool for the study of tissue-specific gene expression. 313 35

Incubation of HTC rat hepatoma cells with the synthetic glucocorticoid dexamethasone rapidly inhibits plasminogen activator (PA) activity and reveals the presence of a specific PA inhibitor (PAI-1). To determine whether the hormonal inhibition of PA activity reflects a decrease in the amount of PA or an increased amount of the inhibitor, or both, we have assayed PA and PAI-1 immunologically. HTC PA was determined to be entirely of the tissue type (tPA), and both free and complexed antigen was quantified by a RIA using rabbit antirat tPA, with rat insulinoma tPA as tracer and standard. PAI-1 was quantified by a Western blot assay using rabbit anti-HTC PAI-1 antibody and purified HTC PAI-1 as standard. Under conditions in which dexamethasone inhibited PA activity by 90%, there was no decrease in the cellular content of tPA antigen. Paradoxically, dexamethasone increased tPA antigen approximately 1.5-fold. Under these same conditions, dexamethasone increased PAI-1 antigen 4- to 5-fold. We conclude that the glucocorticoid inhibition of tPA activity in HTC cells is not secondary to a decrease in the amount of tPA but is secondary to the induction of a specific PA inhibitor.
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PMID:Dexamethasone inhibition of tissue-type plasminogen activator (tPA) activity: paradoxical induction of both tPA antigen and plasminogen activator inhibitor. 313 52

A patient with biopsy-proved biliary cirrhosis and previous gastrojejunostomy and portacaval anastomosis experienced episodes of severe hypoglycemia. She was found to have hyperinsulinemia and hyperglucagonemia. An oral glucose tolerance test showed postgastrectomy hypoglycemia. Results of the intravenous tolbutamide test were diagnostic for insulinoma, but results of the intravenous glucagon test and prolonged fast (96 hours) were not. Failure, on two occasions, to suppress C-peptide normally during insulin-induced hypoglycemia led to a diagnosis of pancreatogenous hyperinsulinemia. The pancreas showed a 10-fold increase in islet volume, with intensely positive staining with anti-insulin and anti-glucagon antiserums in addition to anti-somatostatin and anti-pancreatic polypeptide antiserums. Incidental findings at pancreatic exploration were a mesothelioma, which did not stain with anti-insulin antiserum, and, at autopsy one year later, a hepatoma.
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PMID:Diagnosis of pancreatic islet hyperplasia causing hypoglycemia in a patient with portacaval anastomosis. 699 72

Glucokinase gene regions that are important for liver specific expression of the enzyme have been functionally identified using transient transfection of rat hepatocytes. Maximal luciferase activity was elicited by a reporter plasmid with 3.4 kilobase pairs of genomic DNA flanking the liver glucokinase promoter. Deletion of a gene fragment between -1000 and -600 with respect to the start of transcription resulted in a 60% decrease in luciferase activity. Further reduction, close to background level, occurred upon deletion of a 90-base pair sequence between -123 and -34. Reporter plasmids with the liver glucokinase promoter and any length of flanking sequence were minimally active in INS-1 insulinoma cells, and conversely reporters with the beta-cell-specific promoter were ineffective in primary hepatocytes. In FTO-2B hepatoma cells, a differentiated line expressing many liver-specific traits but not the endogenous glucokinase gene, the promoter proximal region between -123 and -34 markedly stimulated the expression of transfected plasmids above background. However, addition of the flanking region up to -1000 inhibited luciferase expression. The gene fragment from -1003 to -707 was shown to be a bona fide, hepatocyte-specific enhancer by the following criteria: 1) it stimulated reporter expression by more than 10- and 5-fold when inserted directly upstream of the glucokinase TATA box or complete promoter, respectively, regardless of orientation; 2) it stimulated gene expression from the heterologous SV 40 promoter 4-fold; 3) it was also effective from a downstream position; and 4) in contrast to the enhancer effect in primary hepatocytes, the sequence acted as a silencer in FTO-2B cells and was neutral in INS-1 cells. Both the promoter proximal and the enhancer regions were marked by DNase I hypersensitive sites in the chromatin of primary hepatocytes but not hepatoma or insulinoma cells. Seven footprinted elements termed A through G were mapped in the enhancer by the in vitro DNase I protection assay. Elements A-C may bind liver enriched factors, because they were not protected by spleen nuclear extract. In hepatocyte transfection, the downstream half of the enhancer containing elements A-C was about half as effective as the complete enhancer in stimulating glucokinase promoter activity. Site-directed mutagenesis of element A virtually abrogated the activity of the half-enhancer, whereas mutation of element C had a more moderate effect. The sequence between -732 and -578 upstream of the liver start of transcription in the human glucokinase gene displays 79% sequence identity with the downstream half of the rat enhancer. The human gene fragment ligated to the minimal rat liver glucokinase promoter was shown to work as an enhancer in the hepatocyte transfection system.
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PMID:Liver-specific enhancer of the glucokinase gene. 891 May 67

Hepatoid carcinomas are uncommon extra-hepatic neoplasms exhibiting features of hepatocellular carcinoma and they are most frequently described in the stomach. We report a 64-year-old woman with a malignant insulinoma showing focal hepatoid differentiation and biochemical evidence of alpha-fetoprotein (AFP) production. The current case is the first malignant insulinoma with hepatoid differentiation. Resection of the primary tumor followed by regional embolization was peformed. The patient died 22 months after initial presentation. Thus, the presence of hepatoid differentiation in pancreatic tumor should be noted as the tumor may be associated with elevated AFP. The features of pancreatic hepatoid carcinomas are discussed.
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PMID:Malignant insulinoma with hepatoid differentiation: a unique case with alpha-fetoprotein production. 1174 56


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