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)

nm23 was originally identified as an antimetastatic gene, the expression of which was inversely correlated with tumor metastatic potential in rodent model systems. Subsequently, two related human nm23 genes, nm23-H1 and nm23-H2, were identified. The relationship between expression of nm23-H1 and nm23-H2 in hepatocellular carcinoma specimens from 30 patients and metastatic potential was investigated with the use of a quantitative reverse transcription-PCR procedure. The abundance of nm23-H1 and nm23-H2 mRNA was compared with serum alpha-fetoprotein concentration, tumor size (maximum diameter), and histopathological parameters such as portal vein tumor thrombus, intrahepatic metastasis, capsular formation, capsular infiltration, differentiation of tumor cells, and TNM stage. The abundance of nm23-H1 mRNA showed a significant inverse correlation with intrahepatic metastasis and TNM stage. Furthermore, we confirmed that reduced expression of nm23-H1 mRNA was in accordance with a reduced amount of NM23-H1 protein using Western blot analysis. No correlation was apparent between nm23-H2 mRNA abundance and intrahepatic metastasis. These data support the conclusion that nm23-H1 may play a more important role than nm23-H2 in intrahepatic metastasis in hepatocellular carcinoma. Furthermore, nm23-H1 mRNA abundance may be a predictor of intrahepatic metastasis, the most important factor correlated with the metastatic potential of hepatocellular carcinoma.
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PMID:NM23-H1 and NM23-H2 messenger RNA abundance in human hepatocellular carcinoma. 753 Jun

For the purpose of investigating the relationship between the metastatic potential of the tumor as well as the expression of nm23-H1 mRNA, and for determing the location of the positive sites in the cells, tumor metastasis suppressor gene nm23-H1 in human hepatocellular carcinoma (and the nonneoplastic area surrounding the tumor) was detected by in situ hybridization using digoxiginin-labeled nm23-H1 antisense complementary RNA probe. The primary results indicated (i) positive results of in situ hybridization are presence of granules or masses in the cytoplasm; (ii) the less expression of nm23-H1 mRNA, the higher metastatic rate of the human hepatocellular carcinoma (P < 0.05); (iii) expression of nm23-H1 mRNA dose not correlate with some other factors such as tumor size and the background of other liver diseases.
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PMID:[Expression of metastasis suppressor gene nm23 in human hepatocellular carcinoma]. 920 8

Cancer is thought to arise from the accumulation of several genetic mutations in a single cell. These include integration of viral genomes, activation of protooncogenes and inactivation of tumor suppressor genes. HCC is one of the most common cancers in Asia and Africa. Various studies have revealed its association with hepatitis B or C viral infection. While activation of known protooncogenes, such as ras genes does not seem to play an important role, frequent allelic loss on specific chromosomal arms, 4q, 13q, 16q and 17p, indicates that dysfunction of diverse tumor suppressor genes located on these chromosome arms is involved in the development of HCC. An informative p53 mutational spectrum of frequent G to T transversions in codon 249 is found in HCCs from either Qidong, People's Republic of China, or southern Africa. This observation links exposure to aflatoxin B1, a known cancer risk factor in these geographic regions. Recently, we found that expression of syndecan-1, which is a transmembrane heparan sulfate proteoglycan involved in cell matrix interactions and growth factor bindings, was inversely associated with metastatic potential in human hepatocellular carcinoma as like nm23-H1 expression was. Transfection with syndecan-1 gene suppresses invasive activity of hepatoma cells. These data support our hypothesis that syndecan-1 is one of important metastasis suppressor factors in hepatoma cells. PR-39 is a proline-rich antimicrobial peptide which was isolated from a pig small intestine and has been reported to induced syndecan-1 on mouse mesenchymal cells. Transfection with PR-39 gene caused induction of syndecan-1 and altered invasive phenotype and actin structure on hepatoma cells. Syndecan-1 and PR-39 may serve as a basis for design of drug or gene therapy effective against metastasis of hepatocellular carcinomas.
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PMID:[Alteration of genomic structure and/or expression of cancer associated genes in hepatocellular carcinoma]. 949 32

It has been proposed that nm23-H1, a candidate suppressor gene for metastasis, plays an important role in the metastasis of human tumors. In order to investigate its role in the human hepatocellular carcinoma (HCC), 18 matched pairs of tumorous and adjacent nontumorous liver tissues of hepatectomy from patients with HCC were studied by quantitative reverse transcription-PCR. Further analyses of the nm23-H1 gene were also done. The results of these molecular studies were correlated with the clinicopathologic features of the patients. Nm23-H1 transcript was expressed in all neoplastic and adjacent nontumorous liver tissue. The level of expression, however, did not correlate well with the extension or metastatic potential of the tumors. Instead, in 15 (83.3%) of 18 HCC, nm23-H1 expression was higher in the tumorous tissues, compared with the adjacent nontumorous tissues; and significantly higher levels of nm23-H1 mRNA expression was detected in HCC with poor differentiation (Edmonson classification, III and IV) than those with moderate differentiation (I and II). Southern blot analysis of nm23-H1 gene revealed neither amplification nor loss of heterozygosity of all HCC tissues examined. Direct sequencing of the nm23-H1 gene in all HCC tissues detected no mutations. Our findings suggested that increased nm23-H1 mRNA expression is correlated with HCC tumor progression.
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PMID:Significance of nm23 mRNA expression in human hepatocellular carcinoma. 956 75

We investigated the expression and genomic alteration of nm23-H1 (which encodes a nucleoside diphosphate, kinase A) in 12 human hepatocellular carcinomas (HCCs) and four hepatoma cell lines. The expression of nm23-H1 protein was significantly reduced in HCCs with intrahepatic metastasis (72%) compared with expression in HCCs without intrahepatic metastasis (38%). However, in two of three HCCs examined that had marked reduction of nm23-H1 protein, the nm23-H1 mRNA level was not reduced. A hepatoma cell line, HLF (phenotype, poorly differentiated carcinoma) revealed marked reduction of nm23-H1 protein compared with two other hepatoma cell lines, HuH-1 and HuH-2, although the mRNA level was similar in the three cell lines. No allelic deletion of the nm23-H1 gene was detected in the 12 HCCs examined. No point mutation in the coding region of the nm23-H1 gene was observed in any of the 12 HCCs or the four hepatoma cell lines. These findings suggest that: (i) the expression of nm23-H1 protein is inversely associated with high metastatic potential of HCC, (ii) regulation of nm23-H1 expression may occasionally occur at both the transcriptional and post-transcriptional levels in HCC; and (iii) genomic alteration of nm23-H1 is a rare event in HCC.
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PMID:Reduced expression and rare genomic alteration of nm23-H1 in human hepatocellular carcinoma and hepatoma cell lines. 965 16

In HCC specimens from 25 patients, the levels of nm23-H1 and H-ras mRNA were analyzed by quantitative reverse transcription-polymerase-chain reaction (RT-PCR). Tumor microvessel density (MDV), the essential factor of microenvironment and proliferating cell nucleus antigen (PCNA), indexes as tumor cell proliferating in its microenvironment are also analyzed by immunohistochemical methods using antibodies against endothelial protein factor VIII related antigen (F8RA) and antibody PC-10. Results show that The MDV and PCNA index in the group with intrahepatic metastasis is remarkably higher than that in without one (p<0.01), but the abundance of nm23-H mRNA is opposite (p<0.01). The abundance of H-ras mRNA shows little difference (p>0.05). MDV index shows directly relationship with PCNA index (p<0.01), the abundance of nm23-H1 mRNA show an inverse one with PCNA index (p<0.05). We conclude that in HCC, tumor in situ microenvironment, especially a deteriorative one, plays an important selective role. The decline of nm23-H1 mRNA abundance implies the increase of highly potential metastatic cancer cells which adapt to their microenvironment.
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PMID:The abundance of NM23-H1 mRNA is related with in situ microenvironment and intrahepatic metastasis in hepato-cellular carcinoma. 989 72

A new human hepatocellular carcinoma (HCC) cell line with a highly metastatic potential was established from subcutaneous xenograft of a metastatic model of human HCC in nude mice (LCI-D20) by means of alternating cell culture in vitro and growth in nude mice. The line, designated MHCC97, has been cultivated for 18 months and subcultured for more than 90 passages. The line was showed to be of human origin by karyotype analysis. The cells were either grown as compact colonies (in clusters) or as a monolayered sheet with about 31 h of population-doubling time, exhibited typical malignant epithelial in morphology and were positive for alpha-fetoprotein (AFP). Flow cytometric analysis of the cell DNA content showed an aneuploid pattern, and its index was 1.5 as compared to that of normal human peripheral blood lymphocytes. Karyotypic analyses of G- and C-banding techniques revealed that all cells presented chromosome abnormalities in number and structure. The number of cell line MHCC97 chromosome ranged from 59 to 65 with a modal number of 60 and 61. At least two common chromosome markers, i(1q) and der(4)t(4;?)(4pter-->q35::?), were present in all cells, and deletion of Y chromosome also occurred in all cells. The subcutaneous and intrahepatic xenografts were formed and metastatic lesions in lungs were found after the cells were inoculated into nude mice. The rate of metastasis to lungs was 100% using orthotopic inoculation. Reverse transcription polymerase chain reaction products revealed positive expressions of integrin alpha5 and beta1, urokinase type plasminogen activator receptor (uPAR), vascular endothelial growth factor and nm23-H1 mRNAs of cell line MHCC97. Immunostaining of c-Met, uPAR showed strongly positive in both subcutaneous xenografts and lung metastatic lesions; while positive in xenografts and negative in metastatic lesions for integrin alpha5, beta1. E-cadherin and P53 was not expressed either in xenograft or in the metastatic lesions. PCR products of HBsAg and HBxAg were both positive. The cell line MHCC97 still retained some characteristic features of original tumour. Establishment of cell line MHCC97 should be beneficial to the studies of HCC metastatic mechanisms.
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PMID:New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. 1055 51

The effects of all-trans retinoic acid (ATRA) and epidermal growth factor (EGF) on the expression of nm23-H1, a metastasis suppressor gene, were studied in a human 7721 hepatocarcinoma cell line. It was discovered that the expression of nm23-H1 mRNA was up-regulated by ATRA. This was compatible with the observation that the metastasis-associated phenotypes, such as chemotaxic cell migration and invasion, were both reduced in the ATRA-treated and nm23-H1-cDNA-transferred 7721 cells. However, ability of cells to adhere to fibronectin and laminin was not altered identically in the ATRA-treated and nm23-H1-cDNA-transfected 7721 cells. In contrast, the expression of nm23-H1 mRNA in 7721 cells was down-regulated both by the treatment with EGF and by the transfection of c-erbB-2/neu cDNA, which codes a protein homologous to the EGF receptor. EGF is a compound with biological effects opposite to those of ATRA, and c-erbB-2/neu is known to be a metastasis-promoting gene. These results reveal that the metastasis-preventing effect of ATRA may partly result from the up-regulation of nm23-H1, and the metastasis-promoting effects of EGF and c-erbB-2/neu were probably mediated in part by the down-regulation of nm23-H1.
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PMID:Effects of all-trans retinoic acid and epidermal growth factor on the expression of nm23-H1 in human hepatocarcinoma cells. 1066 47

The effects of transfection of the metastasis suppressor gene nm23-H1 and cell-cycle related tumor-suppressor gene p16 on the activity of N-acetylglucosaminyltransferase V (GnT-V) and their relations to cancer metastatic potential were investigated. After transfection of nm23-H1 into 7721 human hepatocarcinoma cells and A549 human lung cancer cells, the activities of GnT-V were decreased by 28%-42% in the cells. In contrast, when p16 was transfected into these two cell lines, the decrease of GnT-V activity was only observed in A549 cells. This was probably to be due to the obvious expression of p16 gene in parental 7721 cells and the deletion of p16 in A549 cells. The decrease of GnT-V mRNA was only observed in nm23-H1-transfected cells, but not in p16-transfected A549 cells, suggesting that these two genes regulated GnT-V via different mechanisms. Horseradish peroxidase (HRP)-lectin staining showed that the 7721 cells transfected with nm23-H1 or the A549 cells transfected with p16 displayed a decreased intensity with HRP-leucoagglutinating phytohemagglutinin and increased intensity with HRP-concanavalin A, indicating the decline of beta1,6 N-acetylglucosamine branching structure on the asparagine-linked glycans of cell-surface and intracellular glycoproteins. The nm23-H1 transfected 7721 cells also displayed some changes in metastasis-related phenotypes, including the increase in cell adhesion to fibronectin (Fn), the decline in cell adhesion to laminin (Ln), and the decreased cell migration and invasion through matrigel. Transfection of antisense GnT-V cDNA into 7721 cells resulted in a decrease of GnT-V activity, an increase of cell adhesion to Fn or Ln, and a decrease in cell migration and invasion through matrigel. These phenotypes bore similarity to those of the 7721 cells transfected with nm23-H1. Our findings indicate that the down-regulation of GnT-V by nm23-H1 contributes to the alterations in metastasis-related phenotypes, and is an important molecular mechanism of metastasis suppression mediated by nm23-H1.
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PMID:Down-regulation of N-acetylglucosaminyltransferase V by tumorigenesis- or metastasis-suppressor gene and its relation to metastatic potential of human hepatocarcinoma cells. 1097 75

AIM:To detect the expression of CD44v6 mRNA and nm23-H1 mRNA in hepatocellular carcinoma (HCC) by in situ hybridization, and to evaluate the relationship between their expression and also relationship between their expressions and tumor invasion and metastasis.METHODS:CD44v6 cDNA probe was synthesized with PCR technique and the nm23-H1 cRNA probe by in vitro transcription. The expression of CD44v6 mRNA and nm23-H1 mRNA was detected by in situ hybridization. RESULTS:In group with high invasion and metastasis potential, the positive rates of CD44v6 mRNA and nm23-H1 mRNA were 80% (8/10) and 40% (4/10),in group with poor invasion and metastasis potential, they were 21.7% (5/23) and 91.3% (21/23).There was a positive correlation between the expression of CD44v6 mRNA and tumor invasion and metastasis potential in HCC (P < 0.01), and a reverse correlation between the expression of nm23-H1 mRNA and tumor invasion and metastasis potential (P < 0.01) and a reverse correlation in the expression between CD44v6 mRNA and nm23-H1 mRNA in HCC (P < 0.01).CONCLUSION: Detection of CD44v6 mRNA and nm23-H1 mRNA may be useful for tumor invasion and metastasis in HCC.
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PMID:Relationship between expression of CD44v6 and nm23-H1 and tumor invasion and metastasis in hepatocellular carcinoma. 1181 33


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