Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Utilization of autotransfusion during tumor resection remains controversial due to viability of carcinoma cells remaining in collected blood. The purpose of this study was to evaluate autotransfusion techniques combined with leukocyte depleting filters (LDF) for removal of hepatocarcinoma cells from autotransfusate. An in vitro model was created by contaminating expired human erythrocytes with cultured hepatocarcinoma (HEP G2) cells. Autotransfusion devices evaluated were Cobe BRAT2, Sorin STAT-P, and Fresenius CATS. Autotransfusate collected from varying processing conditions were filtered using the Pall Leukoguard RS or Pall Purecell RCQ LDF. Carcinoma concentrations were quantified via Coulter Counter technology. The CATS exhibited higher concentrations of cancer cells in the autotransfusate prior to washing, a 449% increase. This was significantly higher than either the BRAT2 or STAT-P, 350% and 315% respectively. Post washing HEP G2 concentrations in the BRAT2 were significantly higher than the STAT-P and CATS. Doubled wash volumes removed more HEP G2 cells in all trials, reaching statistical significance only in the CATS. LDF resulted in a significant 75% reduction of HEP G2 cells, with no difference between filters. While combination use of autotransfusion devices and leukocyte depleting filters did result in a product with concentrated hematocrit, no technique removed all hepatocarcinoma cells.
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PMID:Removal of hepatocarcinoma cells from blood via cell washing and filtration techniques. 1091 73

We report a rare case of biliary cystadenocarcinoma that occurred in the left hepatic lobe of a 62-year-old man and measured 20 cm in its greatest dimension. The neoplastic epithelium consisted of two types of cells: (1) cells with clear cytoplasm containing abundant mucin, and (2) cells with eosinophilic cytoplasm, which in some areas formed nodules with hepatocytoid features (polygonal cell shape, large nuclei with prominent nucleoli, and pseudoglandular structures). Histochemical stains revealed the presence of cytoplasmic mucin in the hepatocytoid areas, whereas immunohistochemical stains clearly showed a biliary phenotype (diffuse positive staining for "biliary type" cytokeratins, rare foci of positive staining with antibody to human hepatocytes (HEP-PAR1), absence of staining for alpha-fetoprotein, and no evidence of canalicular pattern of staining with polyclonal antibody to carcinoembryonic antigen). These findings indicate that areas reminiscent of hepatocellular carcinoma may occur in biliary cystadenocarcinomas. Histochemical and immunohistochemical stains are useful in reaching a definitive diagnosis in such cases.
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PMID:Biliary cystadenocarcinoma with two types of tumour cells. 1114 78

Thrombospondin-1 (TSP-1) is a homotrimeric glycoprotein synthesized in a variety of normal and transformed cells, and secreted into the extracellular matrix. Based on its known effects on the tumor and endothelial cells, TSP-1 was implicated in the tumor growth and metastasis. In the present study, we have demonstrated the expression of TSP-1 in the human hepatocarcinoma cell lines. TSP-1 was detected in human hepatocarcinoma SK-HEP-1, Hep 3B and immortalized human liver Chang cells. Using two different cell lines, SK-HEP-1 and Hep 3B cells, we have studied effects of phorbol 12-myristate 13-acetate (PMA) on TSP-1 expression. TSP-1 synthesis was stimulated by PMA in both cell lines. When the cells were treated with PMA, the TSP-1 mRNA started to increase at 30 min and reached the maximal level at 6 h. TSP-1 induction by PMA was completely inhibited by the pre-treatment of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a potent protein kinase C inhibitor. A TSP-1 promoter-luciferase reporter gene was transcriptionally activated by PMA, as well as by the expression of c-Jun. Among three putative AP-1 recognition sites on the TSP-1 promoter, a deletion of the 1st and 2nd sites caused loss of PMA-induced upregulation, while the 3rd site deletion showed no effect. In subsequent experiments, both the recombinant c-Jun and nuclear proteins induced by PMA have a stronger binding affinity for the 2nd AP-1 recognition site than the 1st and 3rd ones. Our study demonstrated that TSP-1 could be expressed and secreted by human hepatoma cell lines and its expression could be effectively regulated by PMA. We also suggest that AP-1 binding activity through the protein kinase C activation is a critical event for the TSP-1 gene expression and consequently affects production and processing of the protein.
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PMID:Expression of thrombospondin-1 in human hepatocarcinoma cell lines and its regulation by transcription factor Jun/AP-1. 1121 60

The root of Paeonia suffruticosa ANDREWS is an important Chinese crude drug used in many traditional prescriptions. 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), a major component of this crude drug, was found to exhibit in vitro growth-inhibiting effect on human hepatocellular carcinoma cell line, SK-HEP-1 cells. The growth-inhibitory effect was related to the ability of PGG not only to cause a G(0)/G(1) phase arrest but also to suppress the activation of nuclear factor-kappa B. Neither apoptosis nor necrosis was observed in the cells treated with PGG. These findings suggest that PGG could be a candidate for developing a low-toxic anticancer agent.
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PMID:In vitro anti-proliferative effect of 1,2,3,4,6-penta-O-galloyl-beta-D-glucose on human hepatocellular carcinoma cell line, SK-HEP-1 cells. 1167 48

N-(4-hydroxyphenyl)retinamide (4HPR), a chemopreventive and chemotherapeutic retinoid, induces apoptosis in various types of cells. Currently, oxidative mitochondrial damage is thought to cause 4HPR-induced apoptosis, although the exact mechanism has not yet been clarified. 4HPR effectively induces apoptosis in hepatoma cells although the susceptibility differs in a cell-specific manner. Hep-3B and PLC/PRF/5 cells were more susceptible to 4HPR than were Hep-G2 and SK-HEP-1 cells, and the resistance to 4HPR seems to be related to growth inhibition (G(1) arrest). We further observed that 4HPR specifically down-regulates cytochrome c oxidase subunit III (CO III) transcript levels through destabilization of its mRNA and thus decreases the activity of cytochrome c oxidase (complex IV). To explore the mechanism whereby the CO III transcript was decreased by 4HPR, we used adenine nucleotide translocator (ANT) ligands, which modulate mitochondrial transmembrane potential (deltapsi(m)) without altering CO III transcription. Intriguingly, bongkrekic acid, a specific ANT inhibitor, enhanced 4HPR-induced deltapsi(m) disruption, which in turn decreased the level of CO III transcripts, which was accompanied by increases in the generation of reactive oxygen species and in apoptosis. In contrast, atractyloside, an activator of ANT, inhibited those 4HPR-induced effects. Taken together, these results indicate that down-regulation of CO III, a molecular marker of oxidative stress, may result from upstream deltapsi(m) disruption and that ligands of ANT may be capable of modulating 4HPR-induced oxidative stress and apoptosis.
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PMID:Cytochrome c oxidase subunit III: a molecular marker for N-(4-hydroxyphenyl)retinamise-induced oxidative stress in hepatoma cells. 1169 12

We observed that N-(4-hydroxyphenyl)retinamide (4HPR), a chemopreventive and chemotherapeutic agent, effectively induced apoptosis in hepatoma cells. Interestingly, Fas-negative (Hep 3B and PLC/PRF/5) hepatoma cells were shown to be more susceptible to apoptosis induced by 4HPR than were Fas-positive (Hep G2 and SK-HEP-1) hepatoma cells. Thus, we explored the mechanisms underlying 4HPR-induced apoptosis in Fas-defective hepatoma cells. Hep 3B cells stably expressing the dominant-negative Fas-associated death domain (dnFADD) showed no alteration in 4HPR drug susceptibility, but when stably expressing E1B19K, Crm A, or dominant-negative FLICE (dnFLICE), Hep 3B cells were resistant, suggesting that 4HPR-induced apoptosis was mediated by caspase-8 activation. Furthermore, apoptosis could be completely blocked by Z-VAD-FMK (a general caspase inhibitor) or by IETD-CHO (a caspase-8 inhibitor), but was only partially blocked by Ac-DEVD-CMK (a caspase-3 inhibitor), by N-acetyl-L-cysteine (NAC) (an antioxidant), by N-acetyl-leucyl-leucyl-norleucinal (ALLN) (a calpain inhibitor I), or by Z-LEHD-FMK (a caspase-9 inhibitor). Time-sequence analysis of the induction of apoptosis by 4HPR revealed that an initial caspase-8 activation was followed by late mitochondrial cytochrome c release and minor caspase-9 activation, which suggested that caspase-8 activation is the primary upstream regulatory point. Activation of Bid or induction of proapoptotic Bax was not observed during apoptosis. In contrast, Bcl-xL expression was decreased during 4HPR-induced apoptosis. Taken together, these results indicate that 4HPR may be a potential chemotherapeutic drug, which is able to induce apoptosis in Fas-defective hepatoma cells through caspase-8 activation.
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PMID:Activation of caspase-8 during N-(4-hydroxyphenyl)retinamide-induced apoptosis in Fas-defective hepatoma cells. 1173 1

Wogonin and fisetin are flavonoids, which are widely distributed in plants. Our recent study demonstrated that, among seven structurally related flavonoids, wogonin and fisetin showed the most potent apoptosis-inducing activities in human promyeloleukemic cells HL-60. In the present investigation, we performed molecular studies to assess the apoptotic effects of wogonin and fisetin on hepatocellular carcinoma cells SK-HEP-1. Both wogonin and fisetin showed dose-dependent cytotoxic effects on SK-HEP-1 cells, accompanied by DNA fragmentation. Microscopic observation under Giemsa staining showed that wogonin and fisetin, at the dose of 80 microM, induced cellular swelling and the appearance of apoptotic bodies, characteristics of apoptosis, in SK-HEP-1 cells. Furthermore, flow cytometry analysis showed an increase of hypodiploid cells in wogonin- and fisetin-treated SK-HEP-1 cells. These data demonstrated that wogonin and fisetin were effective inducers of apoptosis in SK-HEP-1 cells. Treatment with an apoptosis-inducing concentration of wogonin or fisetin caused induction of caspase 3/CPP32 activity, but not of caspase 1 activity. In addition, a caspase 3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor Ac-YVAD-CHO, reversed the cytotoxic effects of wogonin and fisetin on SK-HEP-1 cells. Further, cleavage of caspase 3 substrates including poly(ADP-ribose) polymerase (PARP) and D4-GDI protein, and decrease of pro-caspase 3 protein were detected in wogonin- and fisetin-treated SK-HEP-1 cells. Increase of p53 protein was associated with wogonin- and fisetin-induced apoptosis; however, a p53-controlled gene, p21(Waf/Cip-1), was only induced in wogonin- (not fisetin-) treated SK-HEP-1 cells. Serum starvation elevated p21(Waf/Cip-1) protein expression, and enhanced the apoptotic induction activity of wogonin (not fiseitn) in SK-HEP-1 cells. Our study has provided molecular evidence to demonstrate that wogonin and fisetin had effective cytotoxic effects through apoptosis induction in hepatocellular carcinoma cells SK-HEP-1; activation of caspase 3 cascade, induction of p53 protein and alternative expression of p21(Waf/Cip-1) protein were involved.
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PMID:Wogonin and fisetin induction of apoptosis through activation of caspase 3 cascade and alternative expression of p21 protein in hepatocellular carcinoma cells SK-HEP-1. 1210 53

The anticancer effects of N-(4-hydroxyphenyl)retinamide (4HPR), a potential chemopreventive or chemotherapeutic retinamide, are thought to be derived from its ability to induce apoptosis. However, the mechanism of apoptosis induced by 4HPR remains unclear. Thus, this study was designed to identify the gene(s) responsible for induction of apoptosis by 4HPR. Apoptosis was effectively induced by 4HPR in human hepatoma cells. Using the differential display-PCR method, a gene involved in the response to 4HPR was identified, and cells in which the expression of that gene was modulated were analyzed for survival, induction of apoptosis, and cell cycle. GADD153, a gene involved in growth arrest and apoptosis, was preferentially expressed in human hepatoma cells as well as in other cancer cells during 4HPR-induced apoptosis. 4HPR regulates GADD153 expression at the post-transcriptional level in Hep 3B cells and at the transcriptional and post-transcriptional levels in SK-HEP-1 cells, when assayed by in vitro transfection and mRNA stability experiments. To determine the role of the GADD153 protein overexpression that is induced by 4HPR, Hep 3B cells with ectopic overexpression of GADD153 were found to be growth-arrested (at G(1)) and readily underwent apoptosis following treatment with 4HPR or even when they reached confluence. N-Acetyl-l-cysteine or GADD153 antisense significantly protected the cells from 4HPR-induced apoptosis, accompanying by the inhibition of GADD153 overexpression. Parthenolide-mediated overexpression of GADD153 resulted in enhanced 4HPR-induced apoptosis. These results suggest that GADD153 overexpression induced by 4HPR may contribute to the anticancer effects (induction of apoptosis and growth arrest) of 4HPR on cancer cells.
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PMID:GADD153-mediated anticancer effects of N-(4-hydroxyphenyl)retinamide on human hepatoma cells. 1213 18

Fifteen crude drugs, Stellaria media Cyrill. (Caryophyllaceae), Calendula officinalis L. (Compositae), Achillea millefolium L. (Compositae), Verbascum thapsus L. (Scrophulariaceae), Plantago major L. (Plantaginaceae), Borago officinalis L. (Boraginaceae), Satureja hortensis L. (Labiatae), Coptis groenlandica Salisb. (Ranunculaceae), Cassia angustifolia Vahl. (Leguminosae), Origanum majorana L. (Labiatae), Centella asiatica L. (Umbelliferae), Caulophyllum thalictroides Mich. (Berberidaceae), Picea rubens Sargent. (Pinaceae), Rhamnus purshiana D.C. (Rhamnaceae) and Hibiscus sabdariffa L. (Malvaceae), which have been used as folk medicine in Canada, were evaluated for their anti-hepatoma activity on five human liver-cancer cell lines, i.e. HepG2/C3A, SK-HEP-1, HA22T/VGH, Hep3B and PLC/PRF/5. The samples were examined by in vitro evaluation for their cytotoxicity. The results showed that the effects of crude drugs on hepatitis B virus genome-containing cell lines were different from those against non hepatitis B virus genome-containing cell lines. C. groenlandica was observed to be the most effective against the growth of all five cell lines and its chemotherapeutic values will be of interest for further studies.
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PMID:In vitro anti-hepatoma activity of fifteen natural medicines from Canada. 1220 64

Methylsulfonyl (MeSO(2)) metabolites of polychlorinated biphenyls (PCBs) and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene (4,4'-DDE), itself a metabolite of the insecticide 4,4'-DDT, are emerging as a major class of contaminants in the tissues of wildlife and humans. We investigated the antiestrogenic capacity and potencies of 3'- and 4'-MeSO(2)-2,2',4,5,5'-pentachlorobiphenyl (CB101) and -2,2',4,5'-tetrachlorobiphenyl (CB49), which are among the most environmentally persistent MeSO(2)-PCBs, and 3-MeSO(2)-4,4'-DDE on estrogen receptor (ER)-dependent gene expression in four cell-based bioassay systems. Congener- and concentration-dependent antagonism of 17beta-estradiol (E2)-induced gene expression, rather than induction of ER-dependent gene expression, was observed for the MeSO(2)-PCBs on lucifierase activity in stably transfected human breast adenocarcinoma T47D cells (ER-CALUX) and vitellogenin (vtg) production in primary hepatocytes from male carp fish (Cyprinus carpio) (CARP-HEP/vtg). 4'-MeSO(2)-CB101 and -CB49 had the highest antagonistic potency (i.e., maximum inhibition of about 70%, LOECs of 1.0 microM and 2.5 microM), whereas 3'-MeSO(2)-CB101 and -CB49 were less antagonistic; the precursor CB101 and MeSO(2)-PCB analog MeSO(2)-2,5-dichlorobenzene had no effect. Relative to the 4-MeSO(2)-PCBs, tamoxifen (IC(50), 0.06 microM and 0.7 microM) was about 40 and 7 times more potent in the ER-CALUX and CARP-HEP/vtg assays, respectively. Congener- and concentration-dependent effects on aryl hydrocarbon receptor-mediated induction of EROD activity (carp hepatocytes), luciferase expression (H4IIE rat hepatoma [H4IIE.luc] cell line), or cell viability were not observed. 3-MeSO(2)-4,4'-DDE was neither estrogenic nor antiestrogenic in either of the bioassays. Inhibitory trends for the MeSO(2)-PCBs in a bioassay based on stably transfected human embryonic kidney cell (HEK293-ERalpha-ERE) were similar to the ER-CALUX and CARP-HEP/vtg bioassays, whereas the antagonism was weaker in a related HEK293-ERbeta-ERE bioassay. Our findings suggest that the 4'-MeSO(2)-PCBs are antiestrogenic in vitro via a reversible or surmountable interaction with fish or human ER, and that the interaction with human ERalpha is apparently favored over ERbeta. MeSO(2)-PCB metabolites are persistent and bioaccumulative contaminants, and therefore, could be potentially active as environmental antiestrogens in wildlife and humans.
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PMID:In vitro antiestrogenic effects of aryl methyl sulfone metabolites of polychlorinated biphenyls and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene on 17beta-estradiol-induced gene expression in several bioassay systems. 1237 85


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