UMLS:C0019204 - FACTA Search

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Query: UMLS:C0019204 (hepatocellular carcinoma)
71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.
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PMID:Anti-angiogenic activity of inositol hexaphosphate (IP6). 1529 68

Vascular targeting is a novel strategy that directs endothelial toxins at tumor vessels expressing specific markers and kills tumor cells by vascular occlusion. Integrin-binding RGD motif has been reported to have a homing property to experimental tumor vasculature. In the present study, we evaluated the effect of vascular targeting by doxorubicin-RGD-4C conjugate in an orthotopic murine hepatoma model. MTT assay showed that dox-RGD-4C conjugates had lower cytotoxicity against MH134 mouse hepatoma cells than free dox. When given intravenously to mice with implanted orthotopic hepatoma, however, the dox-RGD-4C suppressed the growth of hepatoma more effectively than free dox (mean tumor volumes 24 mm(3) vs. 67 mm(3), respectively; p=0.047). Histologic analysis of the hepatoma tissue revealed prominent tumor cell death in the dox-RGD-4C treated group and complete tumor cell necrosis in 40% of cases. Immunochemical staining showed expression of integrin alphav mainly around the tumor nodule. These results show that dox-RGD-4C conjugate has a better antitumor effect in an orthotopic mouse hepatoma model by tumor targeting. Integrin alphav of hepatoma feeding vessels is suggested to be targeted by the dox-RGD-4C conjugate.
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PMID:Tumor targeting by doxorubicin-RGD-4C peptide conjugate in an orthotopic mouse hepatoma model. 1537 78

Type IV collagenase plays an important role in tumor invasion and metastasis through cleaving type IV collagen in the basement membrane and extracellular matrix. In this study a molecule-downsized immunoconjugate (Fab'-LDM) was constructed by linking lidamycin (LDM), a highly potent antitumor antibiotic, to the Fab' fragment of a monoclonal antibody directed against type IV collagenase and its antitumor effect was investigated. As assayed in 10% SDS-PAGE gel, the molecular weight of Fab'-LDM conjugate was 65 kD with a 1 : 1 molecular ratio of Fab' and LDM. The Fab'-LDM conjugate maintained most part of the immunoreactivity of Fab' fragment to both type IV collagense and mouse hepatoma 22 cells by ELISA. By MTT assay, Fab'-LDM conjugate showed more potent cytotoxicity to hepatoma 22 cells than that of LDM. Administered intravenously, Fab'-LDM conjugate proved to be more effective against the growth of subcutaneously transplanted hepatoma 22 in mice than free LDM in two experiment settings. In Experiment I, the drugs were given intravenously on day 1 and day 8. Fab'-LDM at the doses of 0.025 mg/kg, 0.05 mg/kg and 0.1 mg/kg inhibited tumor growth by 76.7%, 93.3% and 94.8%, while free LDM at 0.05 mg/kg inhibited tumor growth by 76.1%, respectively. In experiment II, the drugs were given intravenously on day 4 and day 11, Fab'-LDM at the doses of 0.025 mg/kg and 0.05 mg/kg inhibited tumor growth by 74.2%, 80.9%, while free LDM at 0.05 mg/kg inhibited tumor growth by 60.5%, respectively. In terms of survival time, Fab'-LDM was more effective than free LDM. The results suggest that the molecule-downsized immunoconjugate directed against type IV collagenase is of high efficacy in experimental cancer therapy.
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PMID:Antitumor effects of the molecule-downsized immunoconjugate composed of lidamycin and Fab' fragment of monoclonal antibody directed against type IV collagenase. 1538 78

Data from clinical trails have shown that the antitumoral effect of ONYX-015, an E1B 55kDa-deficient adenovirus, as monotherapy is insufficient. To enhance its efficiency, CNHK200-mE, another E1B 55kDa-deficient adenovirus armed with a mouse endostatin gene was constructed and its antitumoral activities against hepatocellular carcinoma (HCC) in vitro and in vivo were investigated. The selective replication and cytotoxicity of CNHK200-mE in Hep3B and HepGII cells independent of p53 status were confirmed via TCID50 and 3-(4,5dimetylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assays. Potent tumor growth suppression on SMMC-7721 xenografts in nude mice was observed and a synergistic effect of the carrier virus and the therapeutic gene was suggested. Moreover, in comparison with the nonreplicative adenovirus carrying the same therapeutic gene, amplified transgene expression of mouse endostatin in vitro and in vivo were confirmed by Western blotting and ELISA assay. The effective angiogenesis inhibition and replication of CNHK200-mE in nude mice xenografts were demonstrated by immunohistochemistry. In conclusion, the recombinant adenovirus CNHK200-mE is a replication-competent oncolytic virus mediating high expression of therapeutic gene. Because CNHK200-mE is capable of replicating in and lysing HCC cells selectively with effective tumor growth suppression and antiangiogenic activity on HCC xenografts in nude mice, it holds good potential for the treatment of HCC.
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PMID:Potent antitumor efficacy of an E1B 55kDa-deficient adenovirus carrying murine endostatin in hepatocellular carcinoma. 1538 17

Recently, combined chemotherapy with 5-fluorouracil (5-FU) and interferon (IFN)-alpha has been reported to show marked effects in patients with advanced hepatocellular carcinoma. We investigated the genes associated with susceptibility to this combination therapy. The gene expression profiles of eight human hepatocellular carcinoma cells (HepG2, Hep3B, Huh7, Huh6, PLC/PRF/5, HLE, HLF, and SK-Hep1) were evaluated using an oligonucleotide microarray that consisted of 3,800 genes. The 50% growth inhibitory concentration (GI50) values for 5-FU, IFN-alpha, and the combination of 5-FU plus IFN-alpha were determined by the MTT assay. We selected genes that were expressed differentially between the cells with increased susceptibility to the combination therapy and the remaining cells. Relevance networks of the gene expression patterns and GI50 values of the susceptible cells were constructed to find genes associated with susceptibility to the combination therapy. Of the eight cells tested, five showed increased susceptibility to 5-FU plus IFN-alpha compared with 5-FU treatment alone. Among the 3,800 genes, 25 were expressed differentially between susceptible cells and resistant cells. The relevance networks revealed that sensitivity to 5-FU plus IFN-alpha involved the expression of 27 independent genes, which included 10 genes that are commonly associated with sensitivity to 5-FU alone. We selected a set of genes to predict susceptibility to 5-FU plus IFN-alpha combination therapy. We also selected genes that play key roles in the synergistic effect of this combination therapy. These gene sets should prove useful in evaluations of the efficacy and underlying molecular mechanisms of this combination therapy.
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PMID:Genes associated with human hepatocellular carcinoma cell chemosensitivity to 5-fluorouracil plus interferon-alpha combination chemotherapy. 1549 16

Epirubicin HCl is a new anthracycline analog and derivative of doxorubicin. Doxorubicin is a potent anticancer agent, the use of which is limited by its cumulative dose-dependent cardiotoxicity. Epirubicin HCl has more favorable therapeutic index than doxorubicin and possesses less hematologic and cardiac toxicity at comparable doses. Hepatoma G2 cells are a valuable model to study hepatocellular carcinoma and the liver, where drugs are metabolized. The goal of our study was to evaluate the cytotoxic effect of epirubicin HCl on viability of Hep G2 cells measured using the MTT cytotoxicity test. Epirubicin HCl produced a concentration- and time-dependent cytotoxicity to Hep G2 cells. The mechanism of cytotoxicity of epirubicin HCl (IC(50) value of 1.6 mug/ml within 24 h) appeared to involve a production of free radical species since activities of free radical scavenging enzymes (SOD, catalase, Se-dependent GPx) were increased. Addition of SOD prevented cytotoxicity of epirubicin HCl, and also counteracted the apoptosis. DNA fragmentation was determined to evaluate apoptosis. Western blot analysis indicated a decrease in GST-pi expression and increased activity of NADPH-dependent cytochrome P450 reductase which is a major enzyme in the conversion of epirubicin HCl to a free radical. It is proposed that production of reactive oxygen species increased by the treatment with epirubicin HCl can cause lipid peroxidation, which subsequently promotes apoptosis and reduces cell viability. Superoxide dismutase, catalase and glutathione peroxidase must be considered as a part of the intracellular antioxidant defense mechanism of Hep G2 cells against single electron reducing quinone-containing anticancer antibiotics.
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PMID:Epirubicin HCl toxicity in human-liver derived hepatoma G2 cells. 1552 Apr 98

Development of radiation resistance is one of the major reasons that cancer cells do not respond to radiotherapy and the mechanism for resistance is still not clear. Two sublines of human hepatocellular carcinoma Hep G2 cells were established from cells that survived two different irradiation regimes, 2 Gy for 10 days or 10 Gy for 2 days, respectively. Using MTT assay, the radiation conditioned cells were found to be more resistant to gamma-irradiation and have a greater extent of potentially lethal damage repair (PLDR) for radiation than the parent cells. By Western blot analysis, the radiation-conditioned cells were found to overexpress Raf-1 which is known to regulate the radiation resistance of cells. Inhibition of Raf-1 expression by antisense oligonucleotides increased the radiation sensitivity of the radiation-conditioned cells while inhibitors of Ras (L744,832), PI3K (LY294002) and p38 (SB203580) had no effect. Moreover, antisense Raf-1 oligonucleotides also decreased the radiation induced PLDR capacity of the radiation conditioned cells. It is therefore suggested that Raf-1 may induce radiation resistance through an increase in radiation induced PLDR capacity in Hep G2 cells.
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PMID:The role of Raf-1 in radiation resistance of human hepatocellular carcinoma Hep G2 cells. 1554 62

Human hepatoma cell line QGY-7703 was treated with the medium containing 10, 20, 40 and 60 micromol/L carotenoids extracts from Potamogoton crispus L. (CEPC) for 48 h, 96 h and 144 h, respectively. The inhibition rates to hepatoma cells were determined by MTT assay. The results showed the average inhibition rates of the three treatments varied from 0.14%-23.07%, 39.59%-70.61% and 71.65%-87.01%, respectively. After hepatoma cells were treated with the medium containing 10, 20 and 40 micromol/L of CEPC for 24 h, 48 h and 72 h, respectively, many typical morphology features of apoptotic cells were observed by Laser Scanning Confocal Microscope (LSCM), such as the distinct decrease in number and volume of cells, the shrinkage and deformation of cells, the shape of cell nucleuses appearing like crescent even piece, the decrease in area of yellow DNA in cell nuclei. The percentage of hepatoma cells in every phase of cell cycle was analyzed by Flow Cytometer (FCM) after being treated with 10 micromol/L and 20 micromol/L CEPC for 48 h. Compared with the control group, the cells in G0/G1 phase increased 23.8% (P<0.01) and 35.6% (P<0.01) respectively, in S phase decreased relevantly, while the cells in G2/M phase had no significant change. The Ca2+ concentration (fluorescence intensity) in cytoplasm of hepatoma cells was determined by LSCM after being treated with 20 micromol/L CEPC for 48 h. The Ca2+ concentration increased significantly (P<0.01) and was 1.5 times that of control group. These results demonstrated that the CEPC inhibited the proliferation of hepatoma cells QGY-7703 significantly in a dose and time-dependent manner in vitro. The hepatoma cells treated with CEPC were evidently arrested at G0/G1 phase in the cell cycle. The concentration of Ca2+ in test group cells cytoplasm increased significantly, it might be the important cause that CEPC induced the apoptosis of hepatoma cells QGY-7703. This paper provided scientific basis for further studying and developing the function and value of carotenoids in Potamogoton crispus L.
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PMID:[Effects of carotenoids extracts from Potamogeton crispus on apoptosis of human hepatoma cell line QGY-7703 in vitro]. 1583 9

A decoction of Nigella sativa seeds, Hemidesmus indicus root and Smilax glabra rhizome is used by traditional medical practitioners in Sri Lanka to treat cancer and has been shown to prevent chemically induced carcinogenesis in rats. The cytotoxicity of the decoction and the individual plant extracts were tested on the human hepatoma HepG2 cell line. The effects of 24 h incubation with different concentrations (0--50 mg/ml) of the extracts on HepG2 cells were determined. Results from MTT and SRB assays, and [(14)C]-leucine and [(3)H]-thymidine uptake demonstrated that the decoction had a strong dose-dependent cytotoxic activity. The greatest inhibitory effects were observed on DNA synthesis with both the decoction (91+/-S.E. 3.7% inhibition) and N. sativa plant extract (88+/-3.8%) even at low concentrations (5 mg/ml). The three individual plant extracts were cytotoxic in the order of potency N. sativa>H. indicus>S. glabra. Flow cytometric analysis using Annexin V and propidium iodide staining showed that after 24 h exposure to the decoction, cells were in the late stage of apoptosis and/or necrosis. Further experiments are worthwhile to determine the anticancer potential of this plant decoction and its components.
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PMID:Cytotoxic effects of a decoction of Nigella sativa, Hemidesmus indicus and Smilax glabra on human hepatoma HepG2 cells. 1591 74

6-(p-Chlorophenyl)-3-[1-(p-chlorophenyl)-5-methyl-1 H-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazole (TDZ) is a derivative of various substituted s-triazolo[3,4-b]-1,3,4-thiadiazoles, which are associated with diverse pharmacological activities. However, the antitumor activity of TDZ is not well understood. To evaluate its role on tumor cell lines, we have examined the effect of TDZ on two tumor lines: human hepatoma cell (SMMC-7721) in vitro and Sarcoma180 tumor (S180) in vivo. The cytotoxicity of TDZ on human hepatoma cells was assessed using the MTT assay. The inhibition on tumor growth was evaluated by means of trypan blue exclusion test in vitro, and using a Sarcoma180 tumor (S180) animal model in vivo. A scanning electronic microscope was used to discover the morphological changes on cell surface, cell electrophoresis was employed to determine the changes of cell surface negative charges, and alpha-fetoprotein was applied as a biomarker of hepatoma. The effect of TDZ on DNA synthesis was determined by a [3H]-thymidine incorporation assay, and cell cycle distribution by flow cytometry. The IC50 value of TDZ on SMMC-7721 cells was 52.9 microg/ml (48 h). However, TDZ could inhibit the growth of SMMC-7721 cells at concentrations far lower than the IC50 value. Treated with the same low concentrations of TDZ, microvilli on the surface of SMMC-7721 cells decreased obviously, electrophoresis rate of cells reduced from 2.14 microm ms(-1) x V(-1) x cm(-1) of control to 1.54 and 1.56 microm x s(-1) x V-1 x cm(-1), the content of AFP dropped from 205.14 +/- 6.41 ng x mg(-1) Pr to 115.68 +/- 3.47 and 78.57 +/- 2.35 ng mg(-1) Pr, and the DNA replication was inhibited by 26.8% and 45.2%. These results indicated that TDZ may inhibit proliferation of cancer cells by reversing SMMC-7721 cells malignant phenotypic characteristics and inducing redifferentiation. Flow cytometry showed that TDZ-treated cells resulted in a higher proportion of cells in S phase compared with untreated cells, and only when the concentration reached 64 microg/ml, the apoptosis could happen at the rate of 4.2%. Detection of the inhibition of Sarcoma 180 tumor growth in vivo showed that TDZ reduced the tumor weight and 69.08% of the growth was inhibited. TDZ could inhibit the proliferation of tumors in vitro and in vivo; the possible antitumor mechanism might be inducing redifferentiation at a lower dosage on vitro.
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PMID:Redifferentiation of human hepatoma cell induced by 6-(p-chlorophenyl)-3-[1-(p-chlorophenyl)-5-methyl-1 H-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazole (TDZ). 1591 90

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