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)

A large percentage of patients with advanced-stage hepatocellular carcinoma (HCC) have a recurrence of tumor in the liver or lung after primary resection and even after orthotopic liver transplantation. One reason for this may be the presence of small numbers of tumor cells circulating in the blood before surgery or the liberation of tumor cells into circulation during surgical manipulation. We tested this hypothesis by measuring messenger RNA (mRNA) for human albumin gene as a liver cell marker with the highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR) technique. Albumin mRNA was not found in peripheral blood from normal humans (0 of 6), from patients with liver cirrhosis (0 of 10), from other tumors metastatic to liver (0 of 10), or during liver transplant surgery for cirrhosis (0 of 10). In patients with advanced-stage HCC (TNM stages III and IV), albumin mRNA was detected (16 of 17) in peripheral blood. After liver transplantation in the HCC patients, the level of mRNA decreased below the detectable limit (0 of 9). Three of these patients again had detectable mRNA levels when they had recurrence of HCC after liver transplantation. Patients with stage I HCC did not have detectable expression. These results suggest that circulating tumor cells are present in patients with advanced-stage HCC, which may be one of the reasons why these patients have a high incidence of tumor recurrence after apparently definitive surgical resection and even after liver transplantation.
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PMID:Detection of liver cells in peripheral blood of patients with advanced-stage hepatocellular carcinoma. 784 13

The changes in serum prealbumin (transthyretin) and serum albumin in acute and chronic liver diseases were investigated. Albumin has long been used as a useful indicator of liver function but serum prealbumin has recently been noted for its clinical significance in acute liver diseases. Serum prealbumin concentrations and liver function tests (albumin, bilirubin, alanine aminotransferase) were determined on blood obtained from normal donors (n = 148) and from patients suffering from liver diseases (n = 78) such as acute viral hepatitis, chronic active hepatitis, cirrhosis and hepatoma. The mean serum prealbumin concentration in normal subjects was 29.6 +/- 4.82 mg/dl while the mean serum prealbumin concentration in patients with liver disease was greatly reduced (acute viral hepatitis = 15.3 +/- 7.4mg/dl; chronic active hepatitis = 10.2 +/- 6.6mg/dl; cirrhosis = 9.9 +/- 6.4mg/dl and hepatoma = 10.7 +/- 4.2). Albumin concentrations dropped slightly (13% compared to control) in acute viral hepatitis but dropped markedly (28% compared to control) in chronic liver diseases. The study suggests that serum prealbumin concentration might be a more sensitive indicator than albumin in assessing liver dysfunction in acute liver diseases.
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PMID:Prealbumin rather than albumin is a more sensitive indicator of acute liver disease. 806 77

1. The differentiation status of cells is considered to represent an important factor in determining the effects of toxic components. 2. Two rat hepatoma cell lines, MH1C1 and HTC, were used to study differences in the sensitivity to two toxic metals: copper and zinc. 3. The differentiation of the cell lines was characterized using light microscopy, growth pattern, gamma glutamyltransferase (GGT) activity and albumin production as parameters. 4. The MH1C1 cell line was described to be more differentiated. 5. Albumin production in the MH1C1 cells was significantly higher than in the HTC cells whereas the GGT activity was only slightly different. 6. Toxicity of Cu and Zn was compared. Zn appeared to be more toxic to the cells than Cu, when leakage of lactate dehydrogenase and potassium were measured, whereas both metals were equally toxic when expressed as DNA remaining after 24 hr. 7. The MH1C1 cell line appeared to be more sensitive to Cu and Zn than the HTC. 8. The two metals appeared to have different targets in the cell; Cu may affect the nucleus and Zn the cell membrane.
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PMID:Copper and zinc toxicity in two rat hepatoma cell lines varying in differentiation. 809 79

Hepatocellular carcinoma (HCC) is a common type of cancer, with approximately 260,000 new cases each year, and liver cirrhosis is generally considered a major predisposing factor for HCC. However, specific changes of gene expression in liver cirrhosis and HCC remain obscure. The expression of genes for hepatocyte growth factor (HGF), its receptor c-met proto-oncogene, c-myc proto-oncogene, and albumin was analyzed. Gene expression was studied by PCR in seven normal human livers, nine cases of hepatitis C cirrhosis, 12 cases of alcoholic cirrhosis, two cases of liver adenoma, and 12 cases of HCC. HGF and c-met protein were revealed by immunofluorescent staining. HGF mRNA was not expressed in normal livers but was detected in adenomas, in 80% of HCC, and in some cirrhoses. Paraffin-embedded and fresh-frozen tissue samples yielded similar results. Immunohistochemical data correlated with PCR results regarding the overexpression of the HGF/c-met system in HCC. Albumin gene expression was decreased in HCC vs normal livers, consistent with altered function of tumor hepatocytes. The elevated expression of the HGF/c-met system in HCC may play a role in tumor development and/or progression. Tissue localization studies of HGF and its receptor c-met protein support the existence of both autocrine and paracrine mechanisms of action of HGF in HCC vs only a paracrine mechanism in normal liver.
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PMID:Expression of HGF, its receptor c-met, c-myc, and albumin in cirrhotic and neoplastic human liver tissue. 901 Apr 72

The aim of the study was to assess the specificity of albumin-messenger RNA (mRNA)-positive cells in peripheral blood as an indicator for circulating malignant hepatocytes. Albumin-mRNA-positive cells in the peripheral blood mononuclear cell (PMNC) fraction were detected by reverse-transcription polymerase chain reaction (RT-PCR). Albumin-mRNA-positive cells in PMNC were found in 12 of 19 (63%) patients with hepatocellular carcinoma, but also in 22 of 25 (88%) patients with chronic hepatitis without evidence for hepatoma, and in 18 of 19 (94%) of patients with acute viral hepatitis. In addition, 8 of 28 (28%) of healthy control individuals had also albumin-mRNA-positive cells in peripheral blood. PMNC known to be spontaneously negative for albumin-mRNA could be induced in vitro to transcribe albumin-mRNA after activation with a variety of substances such as interleukin-1 (IL-1) plus concanavalin A (Con A), IL-2, bacterial lipopolysaccharide, platelet derived growth factor, alpha-fibroblast growth factor, or hepatocyte growth factor. These results show that the majority of patients with acute and chronic liver disease without evidence for hepatocellular carcinoma has albumin-mRNA-positive cells in their PMNC fraction indicating the nonspecificity of that parameter for the presence of circulating malignant hepatocytes. In addition, in vitro experiments suggest that PMNC are capable of transcribing mRNA for albumin at a low level after activation. In vivo-activated PMNC are likely to be the source of positivity in healthy controls, patients with nonmalignant acute and chronic liver disease, and patients with hepatocellular carcinoma.
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PMID:Lack of specificity of albumin-mRNA-positive cells as a marker of circulating hepatoma cells. 909 94

Discriminant function analysis has been used to investigate the relative value of six biochemical parameters (plasma ferritin, C-reactive-protein, bilirubin, alkaline phosphatase, glutamic oxaloacetic acid transaminase and albumin) in the diagnosis of liver disease. This was done among four groups totalling 70 subjects including healthy controls and patients with acute viral hepatitis, liver cirrhosis and primary hepatocellular carcinoma. Albumin had most value in distinguishing between groups, followed cumulatively by ferritin, alkaline phosphatase, C-reactive protein, bilirubin and glutamic oxaloacetic acid transaminase. However, if data on albumin, alkaline phosphatase, bilirubin and glutamic oxaloacetic acid transaminase had already been routinely collected, there would be no advantage in collecting data on ferritin and C-reactive protein. Any four of the six parameters would be of about equal value in distinguishing between diagnostic groups. When the data on all six biochemical parameters was combined in an optimum way, about 66% of all individuals could be correctly assigned to one of the four groups using biochemical markers alone. While the control subjects and patients with acute viral hepatitis formed a relatively well defined, tight cluster (apart from two patients with acute viral hepatitis), patients with liver cirrhosis and primary hepatocellular carcinoma were almost indistinguishable, using these biochemical parameters. If the latter two groups were pooled, then about 86% of subjects could be correctly classified.
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PMID:Discriminant analysis of biochemical parameters in liver disease. 919 66

We performed interventional angiography (IVA) in a patient with liver cirrhosis (LC) and hepatoma (HCC) who experienced repeated attacks of unconsciousness due to hyperammonemia caused by ileocecal-inferior vena cava (IC-IVC) shunt and succeeded in the treatment. We report the results below. The patient, 53-year-old male, underwent endoscopic injection sclerotherapy for esophageal varix due to LC followed by splenectomy for pancytopenia in 1986. He made good progress. However intraarterial anticancer therapy was conducted for HCC in 1994. From that time hepatic coma began to appear and its frequency gradually increased. Hepatic coma occurred once every 3 weeks from June 1996. He was thus admitted to our hospital. Hematobiochemical testes showed that ammonia level was 297 mcg/dl. Albumin 2.8d/dl, and Total-Bilirubin 10.78 mg/dl. Arterioportography from superior mesenteric artery showed most of portal blood flowed away from the liver though the ileocolic vein to IVC. We decided to conduct IVA for treatment. Specially, a 6Fr balloon catheter was inserted from the right inguinal region into a shunt to the portal vein though IVC by the Seldinger technique. The balloon was inflated in the shunt to close the shunt. Six ml of 5% ethanolamime oleate with iopamidol was injected because retrograde angiography showed that iopamidol was flowed out via testicular vein to IVC. The balloon catheter was retained for 24 hours. Angiography, conducted from the catheter again 24 hours later, showed that the shunt was occluded, blood ammonia level was 71 mcg/dl after occlusion. Hepatic coma was not observed after treatment. We encountered a very rare case who repeated hepatic comas due to IC-IVC shunt and recovered dramatically after IVA.
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PMID:Hepatic coma recovered after interventional obliteration for ileocecal-inferior vena cava shunt--report of one case. 938 49

The possibility that serum ferritin is a secreted protein and an acute phase reactant regulated by inflammatory hormones and iron was examined in a hepatic cell line that secretes plasma proteins. Differentiated rat hepatoma cells released albumin and ferritin into the medium, as determined by rocket immunoelectrophoresis and isolation of ferritin by standard procedures plus immunoaffinity chromatography, following labeling with radioactive amino acid. Administration of interleukin-1-beta (IL-1) or tumor necrosis factor-alpha (TNF) doubled the amounts of ferritin released into the medium over 24 and 48 hours. Together, the cytokines had more than an additive effect. Albumin secretion was diminished by IL-1, but not TNF. Iron, administered as an iron dextran complex or as a 1:1 chelate with nitrilotriacetate (Fe-NTA), also enhanced ferritin release, but had no effect on albumin. Intracellular ferritin concentrations did not change significantly with cytokine treatment, but increased in response to iron. With or without treatments, release of ferritin and albumin from cells into the medium was inhibited by brefeldin A, an inhibitor of Golgi function. The effect of each of the cytokines and of iron on ferritin and albumin was also blocked by dichlorofuranosylbenzimidazole (DRB), an inhibitor of transcription. The stimulatory effect of Fe-NTA on ferritin secretion was diminished by TNF, and this was partially counteracted by IL-1, indicating additional regulatory complexity. These results show for the first time that hepatic cells secrete ferritin, that this ferritin secretion is regulated by iron and inflammatory cytokines, and that the mechanisms of regulation differ from those for intracellular ferritin. The results would explain why serum ferritin increases in inflammation or when iron flux is enhanced.
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PMID:Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron. 938 17

In situ hybridization was used to detect albumin mRNA in normal liver and hepatocellular neoplasms in 20 male B6C3F1 mice between 17 and 24 months of age. Positive signals for albumin were observed consistently in the cytoplasm of hepatocytes in normal liver, particularly in periportal areas. No signals were observed in other cells, such as Kupffer's cells, mesenchymal cells, or bile duct epithelium. Of hepatocellular adenomas, 11/11 (100%) stained positively for albumin mRNA, whereas 14/15 (93%) of primary hepatocellular carcinomas showed positive expression. Albumin mRNA was also detected in extrahepatic metastases of hepatocellular carcinoma, including 9/15 (60%) of pulmonary neoplasms and 5/12 (42%) of metastases at other sites. The pulmonary metastases of hepatocellular carcinoma frequently exhibited a glandular, papillary, or sarcomatous histologic appearance. The presence of albumin in these tumors, lacking characteristic hepatocellular phenotype, is a potential determinant of hepatic lineage. We conclude that in situ hybridization for albumin mRNA in mice is a useful tool in the differential diagnosis of hepatocellular carcinoma, particularly in the case of pulmonary metastasis. This technique may also enable recognition of hepatocyte differentiation in glandular structures with phenotypic features of biliary cells, as seen in mixed hepatocellular-cholangial neoplasms.
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PMID:In situ hybridization demonstration of albumin mRNA in B6C3F1 murine liver and hepatocellular neoplasms. 939 39

For an approach of gene therapy for hepatocellular carcinoma (HCC), transcriptional regulatory sequence (TRS) of either alpha-fetoprotein (AFP) or albumin has been used for targeting cancer cells. To examine the feasibility of using TRSs of these genes for possible gene therapy of HCCs, the cellular distribution of AFP and albumin gene transcripts was studied in 25 cases of surgically removed human HCCs. AFP gene expression was observed in HCC nodules of 13 cases. The expression in HCC was heterogeneous, and the distribution of the transcripts was mostly sparse and spotty. The higher the serum AFP levels, the larger population of the AFP-expressing HCC cells tended to reflect. In noncancerous liver, a slight AFP expression was found by Northern blot analysis, but the transcripts were not detected in the liver sections. In contrast, albumin expression was found in all HCCs as well as in noncancerous hepatocytes. In HCC, the transcripts for albumin were distributed in cancer cells, and the expression varied with nodules. There were more albumin-expressing cancer cells than the AFP-expressing cells. Albumin expression was retained even in poorly differentiated HCC, although the intensity of the signal was not as strong as in more-differentiated HCCs. Metastatic HCC nodules revealed transcripts for both AFP and albumin genes, and those were clearly recognized in the lung tissue. These results suggest that, for gene therapy for HCCs, neither AFP nor albumin are ideal options for targeting HCC cells. AFP-TRS may be used as a transcriptional regulator in selected cases in which AFP gene expression is observed in the cancer nodules. The serum AFP level appears to be an important indicator in selecting cases. Albumin-TRS in conjunction with retroviral vector might be used in limited cases such as HCCs with no AFP expression. However, careful consideration must be taken, because albumin is constitutively expressed in normal hepatocytes, and AFP-expressing nonmalignant progenitor cells possibly exist.
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PMID:Expression of alpha-fetoprotein and albumin genes in human hepatocellular carcinomas: limitations in the application of the genes for targeting human hepatocellular carcinoma in gene therapy. 946 63


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