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)

Previous studies showed that patients with resectable multiploid hepatocellular carcinoma (HCC) had lower overall survival rate and higher recurrent rate than did those with diploid or single aneuploid tumors after hepatic resection. We describe in this study the establishment and characterization of cell lines derived from a single HCC nodule containing multiploid DNA distribution. Two human HCC cell lines, designated HAGS 2.1 and HAGS 2.2, were established by primary culture and single cell cloning methods from a patient with a multiploid HCC tumor. Both cell lines expressed bile canalicular domain-specific antigen of human hepatocyte. The HAGS 2.1 cells were spindle-shaped without prominent intracellular vesicles and had a doubling time of 38 h with DNA ploidy of 4.4 N; cells of HAGS 2.2 were polygonal with many intracellular vesicles and had a doubling time of around 42 h with DNA ploidy of 5.1 N. Hepatitis B surface antigen was detectable in HAGS 2.2 but negative in HAGS 2.1 cells. Both HAGS 2.1 and HAGS 2.2 expressed major histocompatibility complex (MHC) class I antigen, but the former expressed more MHC class II antigen than did the latter. Polymerase chain reaction and subsequent single strain conformation polymorphism analysis disclosed the presence of preS and S regions and the absence of C and X regions of HBV genome in cells of both HAGS 2.1 and HAGS 2.2. We conclude that the establishment of cell lines derived from a single HCC tumor containing multiploid DNA distribution might provide a good in vitro model to study the carcinogenesis and the recurrence mechanism of human hepatocellular carcinoma.
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PMID:Establishment and characterization of two cell lines derived from a single hepatocellular carcinoma containing multiploid DNA distribution. 890 2

The role of the large regenerative nodule (RN) in hepatocarcinogenesis is not clear, although the incidence of hepatocellular carcinoma (HCC) is high in cirrhotic liver. This study was aimed at clarifying the preneoplastic nature of large RN without atypia. We analyzed the clonality of HCCs and large RNs, ranging in size from 0.6 to 1.2 cm, of cirrhotic liver by X-linked human androgen receptor (HUMARA) gene assay, using the principle of random X chromosome methylation and inactivation in females. Eleven cases of HCC and five cases of large RN without atypia from ten female patients were selected. All HCCs, large RNs and paired non-tumorous tissue from adjacent liver were selectively microdissected from deparaffinized hematoxylin and eosin stained slides. Genomic DNA was isolated and digested with Hha I. Polymerase chain reaction (PCR) amplification of the HUMARA gene was performed using a PCR mixture containing [alpha-32P]-dCTP. The PCR products were separated by gel electrophoresis and analysed by autoradiography. HUMARA was informative in nine out of ten female patients. In the informative 10 HCCs from nine patients, 9 HCCs were monoclonal and one case was polyclonal. The HCC case that showed polyclonality contained many inflammatory cells in the tumor. All of the large RNs were polyclonal. No allelic loss of chromosome 18q was present in the large RNs in constrast to the 3 out of 7 HCCs, which showed allelic deletion in chromosome 18q. We conclude that all or most of the cells composing the large RNs without atypia are polyclonal and the size of a nodule may not be important in hepatocarcinogenesis. This clonality assay may be informative for the differentiation between regenerative and preneoplastic nodules in cirrhotic liver.
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PMID:Clonality of large regenerative nodules in liver cirrhosis. 938 17

A combinatorial screening method has been used to identify hairpin ribozymes that inhibit hepatitis B virus (HBV) replication in transfected human hepatocellular carcinoma (HCC) cells. A hairpin ribozyme library (5 x 10(5) variants) containing a randomized substrate-binding domain was used to identify accessible target sites within 3.3 kb of full-length in vitro-transcribed HBV pregenomic RNA. Forty potential target sites were found within the HBV pregenomic RNA, and 17 sites conserved in all four subtypes of HBV were chosen for intracellular inhibition experiments. Polymerase II and III promoter expression constructs for corresponding hairpin ribozymes were generated and cotransfected into HCC cells together with a replication-competent dimer of HBV DNA. Four ribozymes inhibited HBV replication by 80, 69, 66, and 49%, respectively, while catalytically inactive mutant forms of these ribozymes affected HBV replication by 36, 28, 0, and 0%. These findings indicate that the inhibitory effects on HBV replication were largely mediated by the catalytic activity of the ribozymes. In conclusion, we have identified catalytically active RNAs by combinatorial screening that mediate intracellular antiviral effects on HBV.
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PMID:Combinatorial screening and intracellular antiviral activity of hairpin ribozymes directed against hepatitis B virus. 1036 85

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 GB-C/HG (GB-C/HG) and TT viruses (TTV) infections was investigated in selected populations from Gabon using Polymerase Chain Reaction (PCR) and Enzyme Linked Immunosorbent Assay (ELISA) for anti-Envelop 2 (anti-E2) GBV-C/HGV antibodies. Among pregnant women, 29 of 229 (12.6%) were Hepatitis GB virus-C and Hepatitis G virus (GBV-C/HGV) RNA positive (+) and 32 of 81 (39.5%) anti-E2 + versus 8 of 39 (20.5%) TTV DNA +. Among sickle cell anemia patients, 9.7% (3/31) were GBV-C/HGV RNA + versus 22.5% (7/31) TTV DNA +. For tuberculosis patients, the figures were 11.5% (4/35) and 0%. A study of hepatocellular carcinoma cases (n = 27) versus controls (n = 66) did not show significant differences for GBV-C/HGV RNA (10.7% versus 12.1%) and TTV DNA (44.4% versus 30.3%). According to phylogenetic analysis, the 15 GBV-C/HGV strains investigated clustered in group 1, the most common in sub-Saharan Africa whereas TTV sequences (n = 4) mostly clustered in genotypes G1 and one close to genotype G3. In the Gabonese populations investigated, GBV-C/HGV and TTV infections were highly endemic. These data are consistent with the low pathogenicity of these agents.
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PMID:Prevalence and genetic variants of hepatitis GB-C/HG and TT viruses in Gabon, equatorial Africa. 1138 14

Polymerase chain reaction (PCR) select complementary DNA (cDNA) subtraction of hepatitis B x antigen (HBxAg)-positive compared with -negative HepG2 cells resulted in the up-regulated expression of a cellular gene that encodes a transcript of 745 bases and a polypeptide 99 amino acids long. GenBank analysis revealed extensive homology with the amino terminal domain of cellular multidrug resistant proteins (MRP), although overexpression of this gene did not confer an MRP phenotype. In situ hybridization and immunostaining showed colocalized expression with HBxAg in the liver of hepatitis B carriers. Overexpression of this protein stimulated the growth of HepG2 cells in serum-free medium, and partially protected cells from anti-Fas-mediated killing, but did not promote growth in soft agar or tumor formation in nude mice. Introduction of the dominant negative inhibitor of nuclear factor kappaB (IkappaBalpha) into HBxAg-positive HepG2 cells decreased the levels of messenger RNA (mRNA) and protein, suggesting that its up-regulation is nuclear factor kappaB (NF-kappaB) dependent. Hence, HBxAg activation of NF-kappaB may result in the up-regulation of a cellular protein that promotes growth factor-independent survival and protects against Fas-mediated killing. This factor may contribute to the persistence of infected hepatocytes during chronic infection, which is important for the later development of hepatocellular carcinoma (HCC).
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PMID:A cellular gene up-regulated by hepatitis B virus-encoded X antigen promotes hepatocellular growth and survival. 1143 46

Hepatitis C virus (HCV) exposure is due mainly to infected human blood. Most people with acute HCV infection are unable to clear the virus leading to chronic infection that may progress to cirrhosis and hepatocellular carcinoma. HCV genotyping is very useful to optimize the therapy because it helps to identify the patients that need a more aggressive management (e.g., type 1). The aim of this study was to detect the HCV genotype of 915 patients of Central Italy and to analyze the possible change in the prevalence of genotypes not common in Italy, such as type 4. We used a line-probe assay (INNO-LiPA HCV II, Innogenetics) based on reverse hybridization of HCV genome fragments previously amplified by a Polymerase Chain Reaction assay, COBAS System Amplicor HCV monitor version 2.0 (Roche Diagnostics Systems Inc.). HCV type 1 was detected in 448 cases (49.0%), type 2 in 318 cases (34.8%), type 3 in 109 cases (11.9%), type 4 in 33 cases (3.6%) and co-infections in 7 cases (0.7%). In particular, 339 cases (37.0%) showed subtype 1b, 302 cases (33.0%) 2a/2c, 108 cases (11.8%) 3a and 74 cases (8.1%) subtype 1a. The prevalence of type 4 was 3.3% from September 1999 to July 2002 and 4.5% from August 2002 to April 2003. We confirmed that HCV type 1 is prevalent in Central Italy, in particular subtype 1b, followed by type 2a/2c. We also described that the prevalence of type 4 seems to have increased whereas co-infection is a rare event.
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PMID:Prevalence of hepatitis C virus (HCV) genotypes in central Italy. 1498 78

A mixed epithelial and mesenchymal tumor of the liver arising in an adult is rare and is mostly classified as sarcomatoid hepatocellular carcinoma (HCC). In this study, a case of sarcomatoid HCC in an adult with hepatoblastoma (HB)-like features, which produced difficulty in the differential diagnosis between sarcomatoid HCC and mixed HB, is presented. The epithelial component of the tumor composed of poorly differentiated HCC, Edmondson's grade III, and more primitive components, which were embryonal and small cell undifferentiated components of HB-like areas. The small undifferentiated cells surrounded HCC and the embryonal component of HB-like area, and revealed transition partly to areas of rhabdomyosarcoma. A small portion of chondrosarcoma was also noted. Immunohistochemical analysis showed that HCC and the embryonal component of HB-like areas expressed alpha-fetoprotein (AFP) and cytokeratin 8. The small undifferentiated cells were negative for AFP but stained with cytokeratin 8 as well as CD56, which is a marker of primitive cells in many sarcoma and HB. It is not certain whether small undifferentiated cells belong to hepatic progenitor cells or primitive mesenchymal cells. Polymerase chain reaction-single-strand conformation polymorphism analysis for beta-catenin mutation using microdissection revealed no mutation of any components. A review was undertaken of the cases previously reported as adult hepatoblastoma without detailed immunohistochemical study and consider many of them may be sarcomatoid HCC. These primitive and sarcomatoid components would be arising from the dedifferentiation process of HCC.
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PMID:Sarcomatoid hepatocellular carcinoma with hepatoblastoma-like features in an adult. 1514 5

Comparison of human leukocyte antigen (HLA) frequencies in patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and in patients with HCV-associated non-Hodgkin's lymphoma (NHL) has not been addressed previously. To this aim, we investigated the distribution of HLA class II alleles in two selected groups of HCV-infected patients. Group 1 included 50 patients with HCV-associated NHL; group 2 included 29 patients with HCV-associated HCC. A control group included 144 hospitalized patients without NHL or HCC and who were negative for HCV, hepatitis B virus, and human immunodeficiency virus antibodies. Polymerase chain reaction sequence DRB1 and DQB1 specific-primer methods were used. DRB1*1101/DQB1*0301 haplotype, which mainly favors the spontaneous clearance of HCV infection, was lower in HCC subjects than in controls, whereas HLA-DRB1*1104/DQB1*0301, was higher in NHL patients. These findings suggest different pathogenic pathways in HCC and in NHL development. In patients with HCV-associated HCC, a major protective role of DQB1*0301 allele, rather than DRB1*11, was found, probably because of a better HLA class II-associated virus clearance. By contrast, the same allele as HLA-DRB1*04 showed an increase in HCV-associated NHL. These data suggest that NHL and HCC development may be associated to a different response with respect to chronic HLA class II-restricted antigen presentation (perhaps a switch toward CD4+Th2 response in NHL?) or, alternatively, that these alleles could be in linkage disequilibrium to unrelated gene(s), or are in synergy with other immunomodulatory genes that may confer increased risk for NHL.
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PMID:Hepatitis C virus-related hepatocellular carcinoma and B-cell lymphoma patients show a different profile of major histocompatibility complex class II alleles. 1555 90

We investigated hepatitis B virus (HBV) DNA integration and expression of several proteins involved in the cell cycle and apoptosis, including cyclin A, retinoblastoma protein (pRB), Fas-associated death domain protein (FADD), tumor necrosis factor receptor-associated death domain protein (TRADD), and nuclear factor kappaB (NF-kappaB) in HBV-associated hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Archival HCC and LC specimens were obtained from 35 patients each with HBV infection; 5 normal liver specimens used as controls were also obtained. Polymerase chain reaction and Southern blot hybridization were used to detect the integration of HBV DNA in the HCC and LC specimens. The protein levels were determined by Western blot assay. The difference in HBV DNA integration between HCC and LC and correlation between HBV-encoded X protein (Hbx) integration and protein expression were analyzed statistically. HBV DNA was detected in 33 (94%) of the HCC and LC specimens. HBx integration differed in the HCC [24 (69%)] and LC [14 (40%)] specimens (p=0.015). Sixty percent of the HCC specimens and 6% of the LC specimens had increased cyclin A expression. Also, 34, 37, 69, and 77% of the HCC specimens were positive for pRB, FADD, TRADD, and NF-kappaB expression, whereas 80, 60, 100, and 100% of the LC specimens were positive for pRB, FADD, TRADD, and NF-kappaB expression. Significant correlations between HBx integration and the level of expression of cyclin A (r=0.452; p=0.006), pRB (r=-0.419; p=0.012), and TRADD (r=0.470; p=0.004) were discovered. Therefore, integration of HBV DNA occurred frequently in HCC and LC cases with chronic HBV infection, whereas HBx integration occurred more often in HCC than in LC cases (p=0.015). HBx integration and altered expression of genes is a key to apoptosis and may play important roles in HBV-induced hepatocarcinogenesis.
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PMID:Integration of the hepatitis B virus X fragment in hepatocellular carcinoma and its effects on the expression of multiple molecules: a key to the cell cycle and apoptosis. 1564 32


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