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)

30 cases of hepatocellular carcinoma and pericancerous nontumor samples were studied by examining the serial sections for immunohistochemical detection of P21 product accompanying identification of N-ras mRNA by in situ hybridization with biotinylated N-ras cDNA probe and a significant correlation was noticed between the results obtained (P less than 0.02). It was suggested that immunohistochemical detection of ras oncogene P21 product may indicate the expression of ras oncogene. The higher expression of N-ras mRNA of the carcinoma and the non-tumor tissue peripheral to the cancer by in situ hybridization were 53.33% and 28.57% respectively. The positive ratio of P21 were 96.67% and 90.48%.
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PMID:[A comparison study of immunohistochemical detection of ras P21 and N-ras mRNA in situ hybridization in hepatocellular carcinoma and pericancerous nontumor liver tissue]. 164 55

Transfection assay of NIH 3T3 cells was performed with DNAs isolated from ten human PHC (primary hepatic cancer) specimens and a hepatoma 7402 cell line. Positive results were obtained in 7402 and in six out of ten PHC DNAs. Human N-ras gene was identified in transfectants from 7402 DNA and transformed cells from three PHC DNA samples, which had passed more than two cycles of transfection. The expression of N-ras was also remarkably enhanced in six out of nine poly(A)+RNA samples isolated from PHC tissues. P21 synthesis was elevated in 7402 cells as well as in transfectants derived from 7402 cells and PHC DNA. In analysis of PHC DNA, rearrangement and amplification of N-ras gene was observed in two PHC samples. The discrepancy of results of the transfection assay and mRNA expression was discussed. Furthermore, c-myc was also highly expressed in most PHC tissues. It implied that the cooperating activity of N-ras and c-myc might be responsible for the malignant phenotypic alteration in some or most cases in human primary liver cancer.
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PMID:Oncogenes in human primary hepatic cancer. 242 30

The expression of P21, AFP and CEA were detected in human hepatocellular carcinoma and its surrounding nontumor tissues by immunohistochemical staining on serial sections. The significance of AFP and P21 in HCC auxiliary diagnosis was discussed. The results are as follows: (1) AFP and P21 were more closely related with HCC than CEA. Both AFP and P21 were expressed simultaneously in more than half the cases. The distribution of these two antigens in HCC was similar. (2) The positive incidence of AFP in tumor tissues was higher than that in surrounding nontumor tissues, but vice versa for P21. Based on the results of this study, we regard that AFP is a relatively specific marker of HCC, better than P21 in auxiliary diagnosis of HCC. The hepatocytes which surround the tumor and can simultaneously express AFP and P21, are likely to be precancerous cells which have been initiated and possess the ability of neoplastic growth but lack phenotype transformation.
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PMID:[A comparative study of the expression of ras oncogenic protein P21 and oncofetal protein AFP, CEA in human hepatocellular carcinoma (HCC)]. 752 89

In order to explore whether platelet-derived growth factor (PDGF) is involved in hepatocarcinogenesis, expression of PDGF-beta chain and ras P21 were investigated using immunohistochemical method in hepatocarcinoma induced with diethylnitrosamine (DENA). Elevated PDGF-beta chain and P21 protein levels were found in hepatocytes in the early stages after DENA administration. Along with the progression of hepatocarcinogenesis, immunopositive cells were increased with the formation of various foci and nodules and the staining was usually stronger in the peripheral parts of nodules. In addition, PDGF-beta and P21 often expressed simultaneously in the smae lesions, where the cells were also positive for AFP expression. The results suggest that abnormal expression of PDGF might be an early specific event during hepatocarcinogenesis and might be involved in the malignant transformation of the hepatocytes by autocrine as well through ras P21 signal pathways.
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PMID:[The role of platelet-derived growth factor and ras P21 in experimental hepatocarcinogenesis]. 920 9

The death receptor Fas transduces apoptotic death signaling mediated by caspases. In the present study, human hepatoma HepG2 cells showed the Fas-mediated apoptosis mediated by caspase, especially caspase 3, only in the presence of actinomycin D. Interestingly, cytosolic proteins extracted from intact HepG2 cells induced caspase 3 inactivation. Our results reveal that this inactivation was triggered by the direct inhibition of activated caspase 3 by IAP gene family ILP. In addition, a 53 kDa protein was co-immunoprecipitated with anti-human caspase 3 antibody from intact HepG2 cells. This protein was a complex-protein of procaspase 3 and the cell cycle regulator p21WAF1 (p21). P21 bound to only procaspase 3, but not to activated caspase 3. We also demonstrate that p21 protein-loaded HepG2 cells resist to Fas-mediated apoptosis even in the presence of actinomycin D. Here we report that caspase 3 inactivation for the resistance to Fas-mediated apoptosis is induced by a procaspase 3/p21 complex formation and direct inhibition of activated caspase 3 by ILP.
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PMID:Resistance to Fas-mediated apoptosis: activation of caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP. 974 72

We investigated the role of wild-type (wt)-p53 as an inducer of apoptotic cell death in human hepatoma cell lines. Following the retrovirus-mediated transduction of the wt-p53 gene, Hep3B cells lacking the endogenous p53 expression began to die through apoptosis in 4 h. They showed a maximal apoptotic death at 12 h, whereas HepG2 cells expressing endogenous p53 did not. However, the transduction of the wt-p53 gene elicited growth suppression of both Hep3B and HepG2 cells. P21(WAF1/CIP1), a p53-inducible cell cycle inhibitor, was induced, not only in Hep3B cells undergoing apoptosis, but also in HepG2 cells. The kinetics of the p21(WAF1/CIP1) induction, DNA fragmentation, and growth suppression of the Hep3B cells showed that DNA fragmentation and growth suppression progressed rapidly following p21(WAF1/CIP1) accumulation. N-acetyl-cysteine or glutathione, potent antioxidants, strongly inhibited the DNA fragmentation, but did not reduce the elevated level of p21(WAF1/CIP1). These findings suggested that p21(WAF1/CIP1) was not a critical mediator for the execution of p53-mediated apoptosis, although it contributed to the growth inhibition of cells undergoing apoptosis. Furthermore, p53-mediated apoptosis could be repressed by antioxidants.
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PMID:Induction of apoptosis in p53-deficient human hepatoma cell line by wild-type p53 gene transduction: inhibition by antioxidant. 1156 26

Despite a prolongation of patient survival, the overall response of doxorubicin (DX) treatment on patients with hepatocellular carcinoma (HCC) remains modest. This is largely attributed to the development of tumor drug resistance either at the onset or during the course of treatment. To investigate the genetic changes associated with DX chemo-resistance, we examined the cytotoxic effect of DX on a panel of 9 HCC cell lines (HepG2, Hep3B, PLC/PRF/5, and six in-house established, HKCI-1, 2, 3 and 4, C1 and C2). The karyotypic abnormalities were examined by spectral karyotyping (SKY) and the chromosome loci defined were investigated for underlying deregulated genes by positional expression profiling. Quantitative RT-PCR was employed to verify the profiling findings, and also used to examine a number of drug resistance-related candidate genes (MDR1, MRP1, MGMT, PTEN, BCL2, BAX, TP53 and P21). Our results indicated that the cytotoxic effect of DX in cell lines exhibited IC50 values that ranged from sensitive to resistant (0.07 to 3.55 microM). While the overall chromosome aneuploidy did not correlate with DX resistance, aberrations on chromosome 10 demonstrated significant correlation with increasing IC50 (p=0.007). Positional profiling further suggested the consistent down-regulation of CGI-18 and ECHS1 on chromosome 10q. The array findings were substantiated by quantitative RT-PCR, which further pointed to a repressed ECHS1 expression in correlation with DX resistance (p=0.021). Among the candidate genes studied, an inverse relationship of P21 (p=0.034) and BAX (p=0.002) expression with DX resistance was also indicated. Our present study highlights the usefulness of multimodality approaches in identifying genetic markers, and further describes the novel finding of ECHS1 down-regulation in the DX chemo-resistance of HCC.
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PMID:Genetic alterations in doxorubicin-resistant hepatocellular carcinoma cells: a combined study of spectral karyotyping, positional expression profiling and candidate genes. 1549 26

Hepatocellular carcinoma (HCC) is one of the major malignancies in the world. The prognosis of HCC is poor, due to frequent intrahepatic metastasis and tumor recurrence. P21-activated protein kinase (Pak1), a main downstream effector of small Rho GTPases, Rac1 and Cdc42, plays an important role in the regulation of cell morphogenesis, motility, mitosis, and angiogenesis. Here, we show that Pak1 gene was overexpressed in human HCCs. Overexpression of Pak1 in human HCCs was associated with more aggressive tumor behavior in terms of more metastatic phenotype and more advanced tumor stages. In addition, HCC cell line stably expressing Pak1 displayed increased cell motility rates and, conversely, knockdown of endogenous Pak1 expression by small interfering RNA reduced the migration rates of HCC cells. In an established metastatic HCC cell line, we found that Pak1 was overexpressed compared with its primary HCC cell line and this overexpression was associated with higher cell motility. Importantly, we found that c-Jun NH(2)-terminal kinase (JNK) was activated in HCC cell lines overexpressing Pak1. Inhibition of the JNK activity by chemical inhibitor significantly reduced the migration rates of HCC cells via attenuation of paxillin phosphorylation at Ser(178). In conclusion, our results document that Pak1 is overexpressed in HCCs and plays an important role in the metastasis of HCC. The mechanism by which Pak1 induces cancer metastasis may involve activation of JNK and phosphorylation of paxillin.
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PMID:P21-activated protein kinase is overexpressed in hepatocellular carcinoma and enhances cancer metastasis involving c-Jun NH2-terminal kinase activation and paxillin phosphorylation. 1744 71

CpG island methylator phenotype (CIMP) involves the targeting of multiple genes by promoter hypermethylation. Telomerase plays an important role in the development of cellular immortality and oncogenesis. To gain insight into the role of epigenetic aberration of telomerase-related genes in hepatocarcinogenesis, we determined a hypermethylation profile in HCC. We examined the promoter methylation status of 9 genes associated with telomerase activity in 120 HCC, 120 cirrhosis tissues and 10 normal liver tissues by methylation-specific PCR. Assay of telomerase activity was by TRAP-ELISA. The frequency of promoter methylation of each gene was P21 63.3%, P15 42.5%, P16 62.5%, P53 14.2%, RB 32.5%, P27 48.3%, WTI 54.2%, E2F-1 70.8% and P300 65.8% of 120 HCC. Methylation status of P21, P15, P16, WTI and E2F-1 was significantly associated with HCC and nontumor tissues (p < 0.05). CIMP+ was detected in 61.7% (74/120) HCC and 15% (18/120) cirrhosis tissues, no CIMP+ was present in normal liver tissues (p < 0.001). A significant difference between CIMP status and metastasis was been found in HCC (p < 0.001). Results showed that 94.6% (70/74) HCC and 55.6% (10/18) cirrhosis patients with CIMP+ show expression of high telomerase activity than 45.5% (10/22) HCC and 6.25% (1/16) cirrhosis patients with CIMP- (p < 0.001). CIMP lead to high levels of expression of telomerase activity through the simultaneous inactivation of multiple genes associated with telomerase activity by concordant methylation.
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PMID:CpG island methylator phenotype association with upregulated telomerase activity in hepatocellular carcinoma. 1854 60

The objective of this study was to develop a new small molecular peptide, tyrosyl-seryl-leucine (tyroserleutide, YSL), as an anticancer drug. Our study investigated the effects of YSL on human hepatocellular carcinoma and cyclin, and explored its antitumor mechanism in vitro. In-vitro effects of YSL on human hepatocarcinoma cell BEL-7402 were assayed by the MTS (dimethylthiazol-carboxymethoxyphenyl-sulfophenyl - tetrazolium inner salt) method. The ultrastructure of tumor cells was observed by electron microscopy. DNA ladder was used to investigate apoptosis of BEL-7402 cells. The effects of YSL on the cell cycle of BEL-7402 cells were determined by flow cytometry. Expression of PCNA, P21, and P27 were investigated by real-time PCR and western blot in BEL-7402 cells. YSL inhibited the proliferation of BEL-7402 cells in vitro, induced DNA fragmentation, and changed their ultrastructure evidently, resulting in the necrosis and apoptosis of tumor cells. YSL interrupted cell cycle of tumor cells at G0/G1 and postponed their proceedings. YSL markedly enhanced the mRNA and protein expression of P21 and P27, and decreased the expression of PCNA of tumor cells. In conclusion, YSL significantly inhibited the growth of human hepatocellular carcinoma BEL-7402 cells and its anti-tumor effects may result from the upregulation of cyclin P21 and P27, and downregulation of cyclin PCNA.
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PMID:Effects of a novel tripeptide, tyroserleutide (YSL), on cell cycle progression of human hepatocellular carcinoma. 1949 61


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