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)

Copper overload and deficiency are known to cause morphological and functional mitochondrial abnormalities. The reverse transcriptase-polymerase chain reaction (RT-PCR)-based method of differential display of mRNA was used to identify genes with altered expression in cultured human hepatoma cells (Hep G2) exposed to increasing concentrations of copper (0-100 microM, 24 h). Copper regulation of a cloned PCR product, identified as the gene for the mitochondrially encoded cytochrome b, was confirmed by Northern analysis and in situ hybridization. Copper toxicity increased cytochrome b mRNA abundance up to 3.6-fold, and copper chelation reduced it by 50%. Hepatic cytochrome b mRNA was also increased in rats fed a high-copper diet. Thapsigargin treatment resulted in a significant increase in cytochrome b mRNA, suggesting that an increase in intracellular calcium may be involved in the mechanism of copper action. Furthermore, although cyclohexamide (CHX) alone did not increase cytochrome b mRNA, the addition of CHX and copper resulted in a sixfold increase. These data suggest a role for cytochrome b in the response to increases or decreases in hepatic copper.
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PMID:Regulation of mitochondrial cytochrome b mRNA by copper in cultured human hepatoma cells and rat liver. 1053 24

Hepatitis B virus (HBV) infection is a worldwide public health problem. In France, 150,000 individuals are infected with the HBV. Although many are asymptomatic carriers, about 30% have chronic hepatitis, a condition associated with a risk of cirrhosis and hepatocellular carcinoma. Antiviral treatments, most notably interferon alpha, probably modify the natural history of hepatitis B, decreasing the risk of hepatocellular carcinoma and increasing survival. Nucleoside analogs, particularly lamivudine, have also demonstrated potent antiviral activity, which should however be weighed against the increasing risk over time of mutation development in the YMDD region of the DNA polymerase reverse transcriptase. Antiviral therapy monitoring should include clinical safety evaluations and periodic laboratory tests including blood cell counts, transaminase activities, and serum DNA levels. The improving results provided by antiviral drugs should not deflect attention away from the importance of large-scale hepatitis B immunization of neonates, which has been shown to decrease the incidence of hepatocellular carcinoma in areas with high levels of hepatitis B endemicity.
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PMID:[Hepatitis B: epidemiology, natural history, biology, treatment monitoring]. 1060 72

Generally, 0.4-2.5% of patients with chronic hepatitis C virus (HCV) infection develop hepatocellular carcinoma (HCC). HCC occurs more often in patients with cirrhosis and in those with increased liver cell proliferation. HCV-related tumors occur in older patients and often have a less aggressive course than HCC, related to other etiological factors. Many HCV-related HCC are multifocal in origin. However, many tumors grow as a single hepatic nodule for years before generating satellite or distant tumor nodules. The growth pattern varies from one tumor to another, with tumor volume doubling times ranging from 1 to 20 months. Tumor progression and hepatic failure are the leading causes of death in most patients. Using the polymerase chain reaction technique, HCV-RNA has been almost invariably detected in serum and tumor tissue of anti-HCV patients with HCC. In many patients, HCV-RNA was found to belong to the possibly more pathogenic type 1b. However, it is unlikely that HCV plays a direct role in liver tumorogenesis, since no reverse transcriptase activity has been found in infected livers. One current opinion is that HCV may promote cancer through cirrhosis, which is per se an important risk factor for this tumor. In HCV carriers, the risk of developing HCC and having more severe tumor disease may be increased by coexisting hepatitis B virus (HBV) or alcohol abuse, further supporting the idea that both HCC and cirrhosis might be a result of the interplay of several risk factors. HCC could also be the consequence of HCV interacting with cellular genes that regulate cell growth and differentiation, independent of the effect of cirrhosis.
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PMID:Natural history and pathogenesis of hepatitis C virus related hepatocellular carcinoma. 1062 56

We have developed a new assay, ISET (isolation by size of epithelial tumor cells), which allows the counting and the immunomorphological and molecular characterization of circulating tumor cells in patients with carcinoma, using peripheral blood sample volumes as small as 1 ml. Using this assay, epithelial tumor cells can be isolated individually by filtration because of their larger size when compared to peripheral blood leukocytes. ISET parameters were defined using peripheral blood spiked with tumor cell lines (HepG2, Hep3B, MCF-7, HeLa, and LNCaP). ISET can detect a single, micropipetted tumor cell, added to 1 ml of blood. We also demonstrate that fluorescence in situ hybridization can be used to perform chromosomal analyses on tumor cells collected using ISET. Polymerase chain reaction-based genetic analyses can be applied to ISET-isolated cells, and, as an example, we demonstrate homozygous p53 deletion in single Hep3B cells after filtration and laser microdissection. Finally, we provide evidence for the in vivo feasibility of ISET in patients with hepatocellular carcinoma undergoing tumor resection. ISET, but not reverse transcriptase-polymerase chain reaction, allowed analysis of cell morphology, counting of tumor cells, and demonstration of tumor microemboli spread into peripheral blood during surgery. Overall, ISET constitutes a novel approach that should open new perpectives in molecular medicine.
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PMID:Isolation by size of epithelial tumor cells : a new method for the immunomorphological and molecular characterization of circulatingtumor cells. 1062 54

The distribution of hepatitis C virus (HCV) genotypes among Egyptian patients positive for anti-HCV was determined and their influence, when combined with neu-oncoprotein overexpression, on the development of hepatocellular carcinoma (HCC) was examined. The study groups included asymptomatic carriers (ASC) and patients with chronic active hepatitis (CAH) and HCC. HCV genomes were detected in the sera of 27 ASC, 29 CAH and 33 HCC patients known to have HCV infection defined by EIA and recombinant immunoblotting techniques (Inno-LiA) as well as by reverse transcriptase (RT)-PCR. The HCV genotype was determined by a reverse hybridisation technique (Inno-LiPA I and II), whereas neu-overexpression was detected by the Oncogene Science EIA Kit. Eighty-nine patients were eligible for HCV genotyping; 75 patients (84.3%) were infected with a single genotype, including 1a in 11 patients (12.4%), 1b in 2 patients (2.2%) and 2a in 10 patients (11.2%). Genotype 4 (a or c+d) was detected in 51 patients (57.3%) and only one patient had genotype 10a (1.2%). Fourteen patients (15.7%) showed mixed infection; eight of them had 1a+4 (a or c+d) and four had 2a+4 (a or c+d); the remaining two cases had 1a+2a and 1b+2a. The results revealed an increased incidence of genotype 4 in CAH and HCC patients in comparison with ASC. There was also a significant overexpression of neu-oncoprotein in CAH and HCC patients compared with ASC, which was significantly associated with subtype 4 infection. The results suggest that infection with subtype 1a and 4 HCV may be considered a risk factor for the induction of neu-overexpression and subsequent development of HCC.
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PMID:Hepatitis C virus genotyping in relation to neu-oncoprotein overexpression and the development of hepatocellular carcinoma. 1062 30

Quercetin is one of the most abundant of the naturally occurring flavonoids. It has been estimated that about 25-50 mg of quercetin are consumed from the daily diet. The chemopreventive effect of quercetin on dietary carcinogen has been intensely studied in animal models; however, knowledge regarding the molecular mechanism is still limited. In this study, the human hepatoma Hep G2 cell line was used to investigate how quercetin prevents benzo[a]pyrene (B[a]P)-induced DNA adducts. The Hep G2 cells were treated with 10 microM B[a]P for 18 hours in the presence or absence of quercetin. The DNA adduct levels, evaluated by 32P postlabeling, decreased in a dose-dependent manner after treatment with quercetin. Cytochrome P-450 1A1 (CYP1A1) and glutathione S-transferase involvement have been well demonstrated in the modulation of B[a]P-induced DNA damage. From the assays of both enzyme activities, quercetin inhibits CYP1A1-linked ethoxyresorufin O-dealkylase activity more effectively than glutathione S-transferase activity. To elucidate the molecular mechanisms, reverse transcriptase-polymerase chain reaction and Western blot were used to evaluate whether the decrease in CYP1A1 enzyme activity by quercetin is mediated because of alterations of CYP1A1 transcription or mRNA stability. The results indicated that quercetin significantly inhibits B[a]P-induced CYP1A1 mRNA and protein expression. From these findings, we conclude that quercetin suppresses B[a]P-induced DNA damage in human Hep G2 cells by altering CYP1A1 gene expression. Thus we suggest that dietary quercetin may have a long-term preventive effect on chemical carcinogenesis, especially in people who eat a diet rich in fruits and vegetables.
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PMID:Quercetin inhibits benzo[a]pyrene-induced DNA adducts in human Hep G2 cells by altering cytochrome P-450 1A1 gene expression. 1069 72

Loss of heterozygosity of chromosome 10q has been reported in hepatoma. Areas with a high rate of loss of genetic material could harbor putative tumor suppressor genes. PTEN/MMAC1, a candidate tumor suppressor gene located at chromosome 10q23.3, has recently been identified and found to be homozygously deleted or mutated in several different types of human tumors. To determine whether the PTEN/MMAC1 gene is a target of 10q loss of heterozygosity in hepatoma, we examined 42 primary hepatomas for mutations in PTEN/MMAC1 by using nested reverse transcriptase polymerase chain reaction (RT-PCR) of the RNA and single-stranded conformation polymorphism (SSCP) analysis of all genomic exons. Although 2 of 42 hepatoma tissues had aberrant transcripts, 5 matched noncancerous liver tissues also had aberrant transcripts. Southern blot analysis of the entire genomic DNA revealed no genomic change. Therefore, like the TSG101 or FHIT gene, aberrant transcripts of PTEN/MMAC1 using the nested RT-PCR method were a common phenomenon for both cancerous and noncancerous liver tissues, which may not be related to oncogenesis. None of the 42 cases had small deletions, point mutations, or insertions. Our results suggest that the PTEN/MMAC1 gene may not play a role in the pathogenesis of hepatoma.
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PMID:Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in hepatocellular carcinoma. 1070 74

One of the genes that the authors have isolated by a differential display of hepatocellular carcinoma compared to adjacent liver is the alpha6 integrin. alpha6 integrin is the major adhesion receptor for laminin and is suggested to be involved in tumor cell invasion and metastasis. To our knowledge, however, there are no reports on alpha6 integrin expression in esophageal carcinoma. We thus conducted a study to determine its clinicopathologic significance in human esophageal carcinoma. The tumor/normal (T/N) ratio of alpha6 integrin expression was calculated by Northern hybridization in 45 cases of esophageal carcinoma. In selected cases the expression of the alpha6 integrin variants A and B was also investigated by reverse transcriptase-polymerase chain reaction, and immunostaining for alpha6 integrin was performed. The expression levels of alpha6 integrin mRNA in the tumor tissue were greater than those of the corresponding normal tissue in 39 of 45 cases (87%). The overexpression of alpha6 integrin was also recognized by immunostaining. Fifteen cases with a high T/N ratio demonstrated a deeper invasion into the esophageal wall than the 30 cases with a low T/N ratio. Although there was no significant difference, the 15 cases with a high T/N ratio had a tendency for a worse prognosis. The ratio of the two variants (alpha6A/alpha6B) did not show any relationship to survival. The findings imply that alpha6 integrin is overexpressed in human esophageal carcinomas and that alpha6 integrin may play an important role in esophageal tumor invasion.
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PMID:alpha6 integrin expression in esophageal carcinoma. 1071 40

We assessed Stanniocalcin-1 (STC-1) mRNA expression in human normal tissues, various types of human cancer cell lines, and cancer tissues obtained during surgery. Using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay developed to detect STC-1 mRNA, the transcripts were detected in 20 out of 21 cancer cell lines and in all tumor tissues from various types of cancer. Semi-quantitative analyses with multiplex RT-PCR showed that STC-1 mRNA tended to be enhanced in cancer tissues of hepatocellular carcinoma and colorectal cancer compared to background cancer-free tissues. Analysis of blood samples obtained from 11 patients with hepatocellular carcinoma before, after and during hepatectomy showed STC-1 mRNA expression in 8 out of 11 patients at least one time. Normal donor blood samples (n=31) were all-negative for STC-1 mRNA expression. Our results indicate that STC-1 mRNA might be a useful molecular marker for detection of tumor cells in blood from patients with various types of malignancies.
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PMID:Assessment of Stanniocalcin-1 mRNA as a molecular marker for micrometastases of various human cancers. 1071 50

The aim of the study was to clarify the role of telomerase component genes in hepatocarcinogenesis and to examine both the relationship between the expression of telomerase component genes and histological differentiation in hepatocellular carcinoma (HCC) and the relationship between expression levels of telomerase component genes and telomerase activity in HCCs. Telomerase is a ribonucleoprotein enzyme composed of a template RNA and several proteins. Recently, three such telomerase component genes have been identified: human telomerase reverse transcriptase (hTERT); human telomerase RNA component (hTERC); and telomerase-associated protein 1 (TEP1). The expression of these components was evaluated in 34 HCCs and 24 non-cancerous liver tissues by reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of hTERT mRNA was detected in most HCCs, but not in the non-cancerous tissues (P<0.01). Expression of hTERC was detected in both HCCs and non-cancerous tissues, but the expression level in HCCs was higher than that in non-cancerous tissues (P<0.01) and tended to increase as histological differentiation became less marked. The expression level of hTERT mRNA correlated with relative telomerase activity (P<0.01). These results suggest that telomerase reactivation during hepatocarcinogenesis might be regulated by only hTERT and an increase in telomerase activity level in tumour progression might be regulated by both hTERT and hTERC.
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PMID:Expression of telomerase component genes in hepatocellular carcinomas. 1071 26


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