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)

In the present study, the hepatoprotective action of Limonium sinense (Plumbaginaceae) was evident after carbon tetrachloride (CCl(4)) and beta-D-galactosamine (D-GalN), respectively, challenge in rats. The plant materials were divided into two parts: (1) the roots extracted with water (WRE) and (2) the leaves extracted with methanol and fractionated with chloroform (CLE). Both WRE and CLE were extremely flavonoid-enriched extracts. In an CCl(4)-induced acute liver damage study, pretreatment with WRE at 300 mg/kg i.p. and CLE at 100 mg/kg i.p. significantly reduced the amino-transaminases levels of SGOT (p < 0.01) and SGPT (p < 0.01) previously increased by CCl(4) intoxication. In D-GalN-induced acute liver damage study, administration of WRE (300 and 500 mg/kg) or CLE (100 mg/kg) p.o. also significantly reduced the SGOT (p < 0.01) and SGPT (p < 0.01) levels previously increased by D-GalN intoxication. Furthermore, the serum triglyceride level was increased after pretreatment with WRE or CLE previously reduced by D-GalN intoxication. All of the liver function profiles were confirmed to have improvement of liver lesion in histopathological observation. In an acute toxicity test on ICR mice, the LD(50) of WRE was 777.6 mg/kg i.p. An in vitro study showed that CLE possessed a more potent cytotoxicity to human hepatocellular carcinoma cells (Hep3B) (EC(50) = 43.1 micro g/mL) than the other organic fractions, which were fractionated from methanol extracts of the leaves of L. sinense. The present results conclude that L. sinense possesses a hepatoprotective efficacy, and is relatively safe in rats.
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PMID:The hepatoprotective effects of Limonium sinense against carbon tetrachloride and beta-D-galactosamine intoxication in rats. 1291 78

An 18-kDa lectin, with an N-terminal sequence displaying slight similarity to some lectins and fungal immunomodulatory proteins, was isolated from the mushroom Ganoderma capense (Lloyd) Teng. It exhibited more potent mitogenic activity than that of concanavalin A toward mouse splenocytes, and antiproliferative activity toward leukemia (L1210 and M1) cells and hepatoma (HepG2) cells. The isolation procedure entailed ion exchange chromatography on Q-Sepharose, fast protein liquid chromatography (FPLC)-ion exchange chromatography on Mono S, and FPLC-gel filtration on Superdex 75. D(+)-galactose and D(+)-galactosamine specifically inhibited the hemagglutinating activity of the lectin. The hemagglutinating activity of the lectin was not affected over the temperature range 0-100 degrees C and after exposure to 100 degrees C for 60min. The activity was stable in the pH range of 4-11, and after incubation with solutions of various chlorides (from 3.125 to 50mM) including NaCl, KCl, CaCl(2), MgCl(2), ZnCl(2), MnCl(2), and AlCl(3). However, it was potentiated by 12.5-50mM FeCl(3). The lectin was devoid of HIV-1 reverse transcriptase inhibitory and antifungal activities.
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PMID:A mushroom (Ganoderma capense) lectin with spectacular thermostability, potent mitogenic activity on splenocytes, and antiproliferative activity toward tumor cells. 1475 Dec 30

Previous studies showed that Pien Tze Huang, a Chinese folk medicine well known for its therapeutic activity in treating liver diseases, protected the liver against carbon tetrachloride (CCl4)-induced damage in mice. In the present study, natural musk, one of the important ingredients of Pien Tze Huang, was replaced by a formulated substitute, and the new formulation of Pien Tze Huang was shown to have similar chromatographic patterns to the original Pien Tze Huang in gas chromatography-mass spectrometry and high performance liquid chromatography. When used in treating mice with CCl4- or galactosamine-induced liver damage, both the original and new formulations of Pien Tze Huang were found to be able to suppress to a similar extent both the histopathological changes in the liver and the elevation of serum alanine aminotransferase and aspartate aminotransferase. Necrosis, cellular ballooning, microvesicular steatosis and lymphocytes infiltration were all significantly reduced in the damaged liver. In hepatoma cells, both formulations activated the activator protein 1 (AP1) enhancer sequence, indicating that both of them were able to act through the JNK signal transduction pathway. The results of the present study showed that the substitution for natural musk does not affect the hepatoprotective activities of Pien Tze Huang. It is also postulated that both formulations protect the liver through regulating signal transduction in the cell.
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PMID:Substitution for natural musk in Pien Tze Huang does not affect its hepatoprotective activities. 1502 14

Dehydroepiandrosterone (DHEA), one of the major androgens secreted by the adrenal cortex, has been shown to have potential immunoreguratory properties. In this study, we examined the effect of DHEA in a mouse model of hepatitis. Mice were treated with DHEA and injected with concanavalin A (Con A) or lipopolysaccharide (LPS)/D-galactosamine (GalN). Cytokine expression was measured by quantitative RT-PCR and ELISA. Apoptosis was detected by the TUNEL method and by DNA fragmentation analysis. In the DHEA-treated mice, the serum levels of ALT and expression of inflammatory mediators were significantly decreased. The number of apoptotic cells was also much lower than that observed in control, untreated mouse liver tissue. There were fewer tumor necrosis factor-alpha (TNF-alpha)-induced apoptotic cells in H4IIE hepatoma cells treated with DHEA than in non-treated cells. DHEA decreased the expression levels of mRNA transcripts encoding TNF-alpha and iNOS. These results suggest that DHEA can reduce T-cell-mediated injury in the liver as manifest by inhibition of the expression of several inflammatory mediators and hepatocyte apoptosis. DHEA should, thus, be considered as a novel candidate for the therapy of liver injury.
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PMID:A novel therapy for acute hepatitis utilizing dehydroepiandrosterone in the murine model of hepatitis. 1549 18

The study was to develop paclitaxel-loaded formulations using a novel type of self-assembled nanoparticles (P/NPs) composed of block copolymers synthesized by poly(gamma-glutamic acid) and poly(lactide). For the potential of targeting liver cancer cells, galactosamine was conjugated on the prepared nanoparticles (Gal-P/NPs). In the in vitro studies, it was found that both the P/NPs and the Gal-P/NPs had a similar release profile of paclitaxel. The activity in inhibiting the growth of HepG2 cells by the Gal-P/NPs was comparable to that of a clinically available paclitaxel formulation (Phyxol), while the P/NPs displayed a significantly less activity (p<0.05). The biodistribution and anti-tumor efficacy of the prepared nanoparticles were studied in hepatoma-tumor-bearing nude mice. It was found that the groups injected with Phyxol, the P/NPs or the Gal-P/NPs significantly delayed the tumor growth as compared to the control group injected with PBS (p<0.05). Among all studied groups, the group injected with the Gal-P/NPs appeared to have the most significant efficacy in the reduction of the size of the tumor. This is because a large number of the Gal-P/NPs were observed at the tumor site, and subsequently released their encapsulated paclitaxel to inhibit the growth of the tumor. The aforementioned results indicated that the Gal-P/NPs prepared in the study had a specific interaction with the hepatoma tumor induced in nude mice via ligand-receptor recognition. Therefore, the prepared Gal-P/NPs may be used as a potential drug delivery system for the targeted delivery to liver cancers.
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PMID:Paclitaxel-loaded poly(gamma-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer. 1630 94

The cytotoxicity profile of various chemical entities was evaluated using two in vitro hepatocyte models. Liverbeads is a cryopreserved model consisting of primary hepatocytes entrapped in alginate beads. WIF-B9 is a hybrid cell line obtained by fusion of rat hepatoma (Fao) and human fibroblasts (WI38). Various reference hepatotoxicants were tested and ranked according to their equivalent concentration 50 (EC50) for various biochemical endpoints (lactate dehydrogenase (LDH) release, 3-(4,5 dimethylthiazol 2yl)-2,5-diphenyl-2H tetrazolium bromure (MTT) activity, adenosine triphosphate (ATP) and glutathione (GSH) levels). The ranking obtained was comparable in both models and consistent with previously published results on hepatocyte monolayers. Ketoconazole, erythromycin estolate, retinoic acid, telithromycin and alpha-naphthyl-isothiocyanate were among the most toxic chemicals in both models, with an EC50 < 200 microM. Troleandomycin, spiramycin, erythromycin, diclofenac, taurodeoxycholate, warfarin, galactosamine, valproic acid and isoniazid were found to be less toxic. Few marked differences, potentially linked to metabolism pathways, were observed between EC50s in the two models for compounds such as cyclosporine A (10 and > 831 microM) and warfarin (5904 and 1489 microM) in WIF-B9 and Liverbeads, respectively. The results obtained indicate that Liverbeads and WIF-B9 cells are reliable in vitro models to evaluate the hepatotoxic potential of a wide range of chemicals, irrespective of structure and pharmaceutical class.
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PMID:Investigation of the hepatotoxicity profile of chemical entities using Liverbeads and WIF-B9 in vitro models. 1650 61

Our past research developed two N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (Dox) conjugates that became the first synthetic polymer-anticancer conjugates to be evaluated clinically. The first, FCE28068, contained Dox bound to the polymeric carrier via a tetrapeptidic linker (glycine-phenylalanine-leucine-glycine (GFLG)) (Mw approximately 30,000 g/mol; approximately 8 wt % drug), and the second, FCE28069, contained additionally galactosamine (Gal) (Mw approximately 30,000 g/mol; approximately 7.5 wt % Dox) again bound by a GFLG linker. Galactosamine was included to promote hepatocyte/hepatoma targeting via the asialoglycoprotein receptor. Both conjugates showed antitumor activity and were clinically less toxic than free Dox (2-5 fold). However, despite their similar chemical characteristics, the conjugates displayed a significantly different maximum-tolerated dose (MTD) in patients. The aim of this study, therefore, was to use small-angle neutron scattering (SANS) to explore the solution behavior of a small library of HPMA polymer conjugates including FCE28068, FCE28069, and their pharmaceutical formulations, plus as reference compounds HPMA copolymer-GFLG conjugates containing aminopropanol (Ap) or galactosamine (Gal) alone (i.e., without Dox). The SANS data obtained showed that HPMA copolymer-GFLG-Ap conjugates (containing 5 and 10 mol % side chains) showed evidence of polymer aggregation, however, no indication of aggregation was observed for FCE28068 and FCE28069 over the concentration range studied (2.5-50 mg/mL). Clear differences in the scattering behavior for the two conjugates were observed at equivalent concentration. Data were best fitted by a model for polydisperse Gaussian coils, and the HPMA copolymer-Dox conjugate with Gal (FCE28069) exhibited a larger radius of gyration (Rg) (by approximately 2.5 nm) compared to FCE28068. In conclusion, we have shown that SANS will be a valuable tool to elucidate conformation-performance relationships for polymer-drug conjugates.
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PMID:Using small-angle neutron scattering to study the solution conformation of N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates. 1741 85

Physical-chemical surface modifications represent a formidable tool to drive a suitable cell behavior on materials intended to be used in the biomedical field. Plasma processes are among the more powerful methods utilized to modify the surface of materials without altering their bulk intrinsic properties. In particular, by means of plasma treatment processes it is possible to graft chemical functional groups on polymer substrate. Functional groups grafted on the surface can improve per se cell adhesion and can also represent suitable anchor sites for biomolecule immobilization. The aim of this work was to determine the effect of plasma treatment and biomolecule immobilization on Polystyrene (PS) Petri dishes on the behavior of a human hepatocellular carcinoma cell line (HepG2). For this aim Petri dishes were grafted with N-containing groups in order to obtain grafted N-functionalities, to be used as anchor groups for the immobilization of galactosamine. In this way two different modified surfaces, NH(3) grafted polystyrene (PS-NH(3)) and polystyrene owing galactosamine moieties (PS-NH(3)-GalNH(2)), have been obtained. Differences in cell morphology, urea and plasma Fibronectin (pFN) production were clearly observed on HepG2 seeded on PS-NH(3) and PS-NH(3)-GalNH(2). These results highlight the role of specific and non specific cell response in the in vitro study of materials intended to be used for biomedical purposes.
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PMID:The study of specific and nonspecific hepatoma cells behavior by means of plasma-treated substrates. 2052 83

Intracellular targeted conjugates of xyloglucan and mitomycin C (MMC) were synthesized with a lysosomally degradable peptide spacer and galactosamine, a terminal moiety that can be used to target polymeric conjugates to hepatoma. The content of the MMC was about 3.5% (mol) in this conjugate. In an in vitro cytotoxicity experiment, the targeted prodrugs have higher cytotoxicity than free MMC against the drug resistant HepG2 cells. In a human tumor xenograft nude mouse model, the targeted prodrugs generated higher therapeutic effect than non-targeted prodrugs or free MMC. Together, these results suggest that targeted prodrugs, which have improved transfer efficiency and hepatocyte specificity, may be useful for the reversion of drug resistant HepG2 cells.
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PMID:Intracellular delivery of mitomycin C with targeted polysaccharide conjugates against multidrug resistance. 2170 35

Rifampicin (RFP) is a semisynthetic antibiotic derived from the rifamycins and is one of the most commonly used pharmaceutical compounds worldwide in the treatment of tuberculosis. We previously reported that low-dose and long-term oral administration of RFP to 6 hepatitis C virus-related liver cirrhosis patients who were at high risk for presenting with hepatocellular carcinoma (HCC) resulted in a marked suppression of the occurrence of HCC without showing an adverse effect. The underlying mechanism was found to be due to the anticancer effect based on the potent anti-angiogenic properties of RFP. The present study revealed that RFP has an additional hepatocyte-protective effect by lowering the release of hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in chronic hepatitis C patients. Experimentally, we were able to show that RFP had hepatocyte-protective effects in acute hepatocyte disorder models of mice and rats induced by concanavalin A and by D-galactosamine, respectively: RFP significantly prevented an increase in the levels of ALT, AST and lactate dehydrogenase in these animal models. In addition, we found that RFP had a strong anti-oxidant action which was approximately three times stronger than the action of silibinin, an anti-inflammatory agent of human hepatic stellate cells, implicating that the hepatocyte-protective effects of RFP are mediated by its anti-oxidant activity. These results reveal that oral administration of RFP exerts not only a prophylactic effect on the occurrence or recurrence of HCC for an extensive period of time, but also exerts hepatocyte-protective effects on both human chronic hepatitis C and acute hepatocyte disorder in rodent models, and the anti-oxidant activity of RFP is implicated to participate in the latter effects.
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PMID:Hepatocyte-protective and anti-oxidant effects of rifampicin on human chronic hepatitis C and murine acute hepatocyte disorder. 2299 38


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