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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polypeptide growth factors stimulate mammalian cell proliferation by binding to specific cell surface receptors. This interaction triggers numerous biochemical responses including the activation of protein phosphorylation cascades and the enhanced expression of specific genes. We have identified several fibroblast growth factor (FGF)-inducible genes in murine NIH 3T3 cells and recently reported that one of them, the FGF-inducible 14 (Fn14) immediate-early response gene, is predicted to encode a novel, cell surface-localized type Ia transmembrane protein. Here, we report that the human Fn14 homolog is located on chromosome 16p13.3 and encodes a 129-amino acid protein with approximately 82% sequence identity to the murine protein. The human Fn14 gene, like the murine Fn14 gene, is expressed at elevated levels after FGF, calf serum or phorbol ester treatment of fibroblasts in vitro and is expressed at relatively high levels in heart and kidney in vivo. We also report that the human Fn14 gene is expressed at relatively low levels in normal liver tissue but at high levels in liver cancer cell lines and in hepatocellular carcinoma specimens. Furthermore, the murine Fn14 gene is rapidly induced during liver regeneration in vivo and is expressed at high levels in the hepatocellular carcinoma nodules that develop in the c-myc/transforming growth factor-alpha-driven and the hepatitis B virus X protein-driven transgenic mouse models of hepatocarcinogenesis. These results indicate that Fn14 may play a role in hepatocyte growth control and liver neoplasia.
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PMID:The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas. 1075 51

A ribozyme (RZ) gene targeting c-myc mRNA was synthesized and cloned. Cleavage reaction showed that cleavage of the RZ was efficient and specific. The RZ gene-containing retrovirus vector pDOR-RZ was transfected into HCC-9204 hepatoma cells, which constitutively express high levels of c-myc using Lipofectamine. Positively transfected cells were selected using G418. In situ hybridization showed that both pDOR-RZ and pDOR vectors had been integrated into the chromosome of HCC-9204 cells. Dot blot hybridization indicated that expression of the RZ was only evident in pDOR-RZ-transfected HCC-9204 cells. Avidin-biotin complex enzyme-linked immunosorbent assay showed that c-myc expression was down-regulated. Chromatin aggregation into compact masses, cytoplasmic vacuole degeneration, and blurring of cytoplasm structure were observed by transmission electron microscopy in HCC-9204-RZ cells. These results suggest that the use of a c-myc mRNA cleaving enzyme could be most effective in tumor cells that are highly proliferative and constitutively express high levels of c-myc.
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PMID:Inhibition of cell proliferation in HCC-9204 hepatoma cells by a c-myc specific ribozyme. 1076 46

Most gene expression methods often involve cumbersome steps or use expensive facilities. Additionally, some of the techniques, such as cDNA biochip, cannot define the sub-population of tissue from which the amplified cDNA was made. Here we present a rapid and high throughput screening method for analyzing the pattern of gene expression of tumor-infiltrating lymphocyte (TIL), which can minimize manipulations in cloned DNA sequencing and in bioinformatics. The pattern of TIL gene expression was studied in one ovarian cancer and one liver cancer. Our results have demonstrated that TILs have three different gene expression profiles: the first set of genes is involved in cell proliferation and mitogenic stimulation, such as c-myc and IL-8, LD78, MIP-1beta, insulin-induced protein and AH-receptor; the second set of genes includes those involved in attachment of lymphocytes to endothelium and extravasation into tumor tissues such as P-selectin ligand and integrin; and the third set, which includes genes such as the perforin, FAS ligand and granzyme B, is related to cytotoxic function to tumor cells. The patterns of TIL gene expression obtained from two specimens are marginally different and can be used in explaining the basis of molecular mechanisms regulating cellular interactions and cytotoxicity.
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PMID:Identification of mRNAs expressed in tumor-infiltrating lymphocytes by a strategy for rapid and high throughput screening. 1102 87

c-Myc has been documented to be both a positive and a negative signal for the induction of apoptosis. It is well known that overexpression of the c-myc gene induces apoptosis of normal cells, but the result of a reduction in its expression is not fully understood. We examined whether a reduction in c-myc expression would induce apoptosis in human liver cancer cells. Specifically, antisense and sense oligodeoxynucleotides (oligos) against the human c-myc mRNA were synthesized, mixed with a liposome reagent at various ratios, and were applied to the liver cancer-derived cell lines, HCC-T, HepG2, and PLC/PRF/5. To exclude effects resulting from using oligos, plasmid vectors expressing the full-length c-myc cDNA in both sense and antisense orientations under the control of the Cre/loxP system were generated. Monoclonal cell lines including these plasmid vectors were produced and Cre was supplied by adenovirus infection. Apoptosis was determined morphologically and c-Myc and Bcl-2 expression was examined by Western blotting. The antisense myc significantly inhibited the proliferation of the cells within two days, while neither the liposome reagent alone nor sense myc did so. Most of the cells were rounded up by the antisense-treatment and nuclear fragmentation and DNA ladder formation were detected after two days in antisense c-myc-treated cells. Antisense c-myc largely reduced c-Myc and partially Bcl-2 expression; overexpression of Bcl-2 partially rescued from apoptosis in HCC-T and HepG2 cells. These results suggest that the massive reduction in c-myc mRNA induces apoptosis in liver cancer cell lines and consequent decrease in Bcl-2 enhances the cell death. c-Myc reduction under the Cre/loxP switching system may be a useful tool for the clarification of c-myc-related cellular mechanisms in differentiation and proliferation.
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PMID:Reduction of c-myc expression by an antisense approach under Cre/loxP switching induces apoptosis in human liver cancer cells. 1138 22

Prothymosin-alpha (PTalpha) is known to play a role in cell proliferation, and the PTalpha mRNA level may reflect the degree of proliferation of tumor cells. It has been reported that PTalpha mRNA levels are higher in human colon and liver cancer tissues than in the adjacent normal tissues. We examined the mRNA levels of PTalpha and c-myc in 20 lung cancers, using Bas 2500Mac systems. The PTalpha and c-myc mRNA levels in lung cancer tissues were higher than those in normal lung tissues; however, the PTalpha mRNA levels did not correlate with the stage or pathological subtype of the lung cancer and there was no correlation between the expression of PTalpha and c-myc. PTalpha mRNA overexpression in lung cancer was correlated with a poor prognosis.
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PMID:Expression of the prothymosin-a gene as a prognostic factor in lung cancer. 1175 95

AIM:To study hepatocarcinogenesis of hepatitis C virus (HCV).METHODS: Expression of HCV antigens (CP10, NS3 and NS5) and several cancer-associated gene products (ras p21, c-myc, c-erbB-2, mutated p53 and p16 protein) in the tissues of hepatocellular carcinoma (HCC, n = 46) and its surrounding liver tissue were studied by the ABC(avidin-biotin complex) immunohistochemical method. The effect of HCV infection on expression of those gene products in HCC was analyzed by comparing HCV antigen positive group with HCV antigen negative group.RESULTS:Positive immunostaining with one, two or three HCV antigens was found in 20 (43.5%) cases,with either of two or three HCV antigens in 16 (34.8%) cases, and with three HCV antigens in 9 (19.6%) cases.Deletion rate of p16 protein expression in HCC with positive HCV antigen (80%, 16/20)was significantly higher than that in HCC with negative HCV antigen. Whereas no significant difference of the other gene product expression was observed between the two groups.CONCLUSION:HCV appears related to about one third of cases of HCC in Chongqing, the southwest of China, and it may be involved in hepatocarcinogenesis by inhibi ting the function of p16 gene, which acts as a negative regulator of cell cycle.
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PMID:Effect of HCV infection on expression of several cancer-associated gene products in HCC. 1181 78

There is considerable evidence that reactive oxygen species (ROS) have a causative role in chronic hepatic injury and cancer development via direct and indirect mechanisms. Estrogens produce free oxygen radicals through redox cycling and affect cell proliferation, also in the liver. We are presently involved in evaluating the possible relationship between estrogens receptor expression, type of receptor, oxidative DNA damage and c-myc in chronic liver disease. The data on DNA adducts, c-myc mRNA and variant estrogen receptor in patients with HCV- or HBV-related chronic liver disease are suggesting that those positive for variant liver estrogen receptor present higher genomic oxidative damage, as reflected in 8-OHdG levels. We are also observing that patients with chronic hepatitis and cirrhosis, when positive for variant estrogen receptor, present higher c-myc m-RNA expression, a factor reportedly associated with increased genomic instability, augmented cytoproliferation and carcinogenesis. Our own and other author's data are shedding new light on estrogen pathophysiology, liver damage and hepatic cancer.
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PMID:Estrogens receptors and oxidative damage in the liver. 1216 Oct 6

Previous work from our laboratory has implicated oxidative DNA damage and genetic instability in the etiology of transforming growth factor-alpha (TGFalpha)/c-myc-associated hepatocarcinogenesis. In contrast, oxidative DNA damage was lower in c-myc single-transgenic mice, consistent with less chromosomal damage and with later and more benign tumor formation. We examined whether defects in the DNA repair pathways contribute to the acceleration of liver cancer in TGFalpha/c-myc mice. A cDNA expression array containing 140 known genes and multiplex RT-PCR were used to compare the basal levels of expression of DNA repair genes at the dysplastic stage. Thirty-five percent (8/23) and 43% (10/23) of DNA repair genes were constitutively up-regulated in 10-week-old TGFalpha/c-myc and c-myc transgenic livers, respectively, compared with wild-type controls. The commonly up-regulated genes were OGG1 and NTH1 of base excision repair; ERCC5, RAD23A, and RAD23B of nucleotide excision repair; and RAD50, RAD52, and RAD54 involved in DNA strand break repair. Additional treatment with a peroxisome proliferator, Wy-14,643, known to increase the level of oxidants in the liver, failed to induce a further increase in the expression level of DNA repair enzymes in TGFalpha/c-myc but not in c-myc or wild-type livers. Moreover, expression of several genes, including Ku80, PMS2, and ATM, was decreased in TGFalpha/c-myc livers, suggesting a fault or inefficient activation of the DNA repair pathway upon induction of oxidative stress. Together, the results show that DNA damage response is attenuated in TGFalpha/c-myc mice, creating a condition that may contribute to acceleration of liver cancer in this model.
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PMID:Dysregulation of DNA repair pathways in a transforming growth factor alpha/c-myc transgenic mouse model of accelerated hepatocarcinogenesis. 1274 74

An orthotopic xenograft tumor model of hepatocellular carcinoma was created by injection of Hep 3B cells directly into the liver parenchyma of nude mice. Tumors were localized primarily in the injected lobe of the liver, beginning from the third week after tumor cell implantation. Thereafter, tumors grew rapidly, and animals usually died from hepatocellular carcinoma within 2 months. Insulin-like growth factor II, an embryonic growth factor and mitogen, is overexpressed in these tumors at both mRNA and protein levels. Oncogenes, such as c-myc, c-fos, and c-jun, are also up-regulated in this model. alpha-Fetal protein can be detected shortly after implantation and correlates with tumor growth, and measurement of serum alpha-fetal protein serves as an early biomarker to monitor the effect of antitumor therapy. Using this model, we have shown that inhibition of insulin-like growth factor II expression by a short methylated oligonucleotide prolongs survival. This in situ tumor model thus provides a fast, reliable, and reproducible means to study the therapeutic effect of inhibitors of growth factors and oncogenes in liver cancer.
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PMID:A novel orthotopic tumor model to study growth factors and oncogenes in hepatocarcinogenesis. 1285 52

Heterocyclic amines are potent mutagens and carcinogens formed in cooked protein rich foods. In this study, we screened liver tumors induced by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) in CDF1 mice for beta-catenin and APC mutations and other genetic alterations shown to occur in human hepatocellular carcinomas (HCC), including mutations in the p53 and H-ras genes, c-myc amplification and E-cadherin promoter methylation. SSCP followed by direct DNA sequencing revealed mutations in exon 2 of the beta-catenin gene in 2 of 16 liver tumors (12.5%). Promoter methylation of the E-cadherin gene was detected in one liver tumor induced by MeIQ. There were no mutations in the mutation cluster region of the APC gene, in exons 5-8 of the p53 gene, or in codons 12, 13 and 61 of the H-ras gene, nor c-myc amplification in any of liver tumors induced by MeIQ. These data indicate that except for the occasional disruption of the Wnt pathway through beta-catenin mutations, the genetic pathways involved in the development of HCC differ significantly between human liver cancer and tumors induced in mice by MeIQ, but do not rule out the possibility that heterocyclic amines constitute a carcinogenic risk factor in humans.
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PMID:Beta-catenin mutations in liver tumors induced by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline in CDF1 mice. 1289 27


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