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)

To determine whether differentiation therapy is useful in treating patients with hepatoma, we assayed the effects of 25-hydroxycholesterol (25-OH) and/or all-trans retinoic acid (ATRA) on rat AH136B ascites hepatoma cells. Flow cytometric DNA analysis showed that treatment of cells with 25-OH alone induced entry into the sub-G1 phase in a dose-dependent manner. While ATRA alone was ineffective, it enhanced the activity of 25-OH. Condensed and fragmented nuclei occurred mainly in cells treated with 25-OH (4 microg/ml). When cells treated with 25-OH (4 microg/ml), or 25-OH (4 microg/ml) + ATRA (1 microM) were transplanted into Donryu rats, we found that tumor development was completely inhibited; in contrast, rats administered the methanol-treated AH136B cells developed tumors. These findings suggest that AH136B cells in the sub-G1 phase can not recover tumorigenicity, and that the administration of a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, such as 25-OH, and ATRA may be effective in treating patients with hepatoma.
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PMID:Suppression of rat liver tumorigenesis by 25-hydroxycholesterol and all-trans retinoic acid: differentiation therapy for hepatocellular carcinoma. 1042 41

The single cell gel electrophoresis assay (comet assay) is an inexpensive, rapid and highly sensitive method for the determination of DNA damage, crosslinks, and alkaline-labile lesions in individual cells. A limitation of the procedure is that the microelectrophoretic gels must be scored rapidly as the comet configuration deteriorates on storage due to dehydration of the agarose and diffusion of DNA. The objectives of this study were firstly to evaluate drying regimes as rapid and simple methods of preservation of the microgels as close to their original fresh state as possible, and secondly to examine the effects of storage of the slides. Human hepatoma (HepG2) cells challenged for 30 min with hydrogen peroxide (H(2)O(2)) were used in the study. Microgel slides were prepared and evaluated immediately, or after drying with or without a methanol fixation step. Microgels that were dried at a variety of temperatures (22-50 degrees C) and re-hydrated did not differ in the values obtained for H(2)O(2)-induced DNA damage when compared to fresh samples. Samples could also be continually dried and re-hydrated over a period of up to 3 months with no obvious loss of information. In conclusion, drying of microgels represents a simple and inexpensive method of preserving comet assay slides.
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PMID:Preservation of comet assay slides: comparison with fresh slides. 1052 3

White sucker (Catostomus commersoni) caged for 3 days in a bleached kraft mill effluent (BKME) stream had elevated mixed function oxygenase (MFO) activities 15-90 fold those of fish caged in a reference stream. Liver composites of male and female fish were ground and extracted with dichloromethane (DCM), methanol or 50% DCM/methanol, and tested for MFO activity in rat hepatoma cells (H4IIE). There was no difference in the potency of H4IIE EROD induction among the three solvents, so DCM extracts were split into 31 fractions using reverse phase high pressure liquid chromatography (HPLC). H4IIE MFO activity was elevated in several fractions, with three early peaks and several later peaks of induction, indicating several classes or compounds causing MFO induction were present in the fish livers. Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and chlorinated diphenylethers (CDPEs) were detected in several late-eluting fractions, but concentrations were not high enough for these compounds to be solely responsible for the observed induction. Induction by liver extracts decreased as cell exposure times increased (24, 48 or 72 h), suggesting that some inducers were more easily metabolized and eliminated from the H4IIE cells. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2378-TCDD) had similar potency over 24, 48 and 72 h, as it was relatively resistant to metabolism.
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PMID:Isolation of MFO inducers from tissues of white suckers caged in bleached kraft mill effluent. 1087 27

Swertia chirata Buch-Ham. (Gentianaceae), one of the oldest medicinal herbs of India, is a source of the Indian ayurvedic drug 'chirata' used for the treatment of liver disorders and malarial fevers. In this study, eight species of Swertia were collected. Each of the dry whole plant was extracted into methanol, the aqueous extract of which was sequentially extracted into hexane, chloroform and butanol extracts. The extracts were screened for their anti-hepatotoxic activity against carbon tetrachloride (CCl4) and paracetamol (acetaminophen (AAP)) toxicity in primary monolayer cultures of rat hepatocytes. The primary cultures, 2.5 x 10(6) cells /3 ml medium/60 mm collagen-coated plates, were exposed to 2.5 mM CCl4 or 12 mM AAP in the presence or absence of plant extracts (100 microg/ml culture medium). Cells and medium were harvested after 22 h of treatment for the assay of cellular reduced gluthathione (GSH) content and leakage of lactate dehydrogenase as biological end-points of toxicity. Both CCl4 and AAP at the indicated concentrations reduced GSH by almost 50 and 80%, respectively, while the enzyme leakage was almost 15% above the untreated control. Hexane and methanol extracts of most of the species in general offered relatively good protection. The anti-hepatotoxic activity, nevertheless, was evident in all Swertia species against both the toxicants. However, Swertia purpurascens, Swertia chirata, Swertia paniculata and Swertia cordata exhibited better activity compared with other species investigated. In addition, influence of various extracts (10-100 microg/ml medium) was examined on cellular growth of rat Reuber hepatoma cell line H4IIEC3/G-. Except for the butanol extract of S. chirata, no other extracts exerted toxicity in terms of neutral red uptake by the cells.
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PMID:Screening of various Swertia species extracts in primary monolayer cultures of rat hepatocytes against carbon tetrachloride- and paracetamol-induced toxicity. 1129 58

Based on the ability of bile acids for vectorializing the cytostatic activity of other agents, we have designed and synthesized a new bile acid cholylglycinato Au(III) complex, named Bamet-A1. It has been characterized by means of EA (elemental analysis), FT-IR, NMR, FAB-MS (fast atom bombardment-mass spectrometry) and Vis-UV techniques. This characterization allowed us to propose a structure of the type [Au CG(O) CG(N,O) Cl] for the neutral complex, which has the composition C522H84N2O12AuCl and is very soluble in water, methanol, ethanol and DMSO (dimethylsulfoxide). The study in aqueous solution suggested a redox process for its transformation, which is accompanied by the appearance of colloidal gold phase. The behavior in 4 mM NaCl water (in order to mimic the cytoplasmatic fluid) was similar to that observed in water, while in a 150 mM NaCl (similar to extracellular fluid and serum), the apparition of a dark blue precipitate was observed. This complex displays fluorescence, which does not change when incubated with DNA obtained from E. coli. Bamet-A1 was found to inhibit the growth of a variety of cell lines. The cytostatic effect was mild against human hepatoma HepG2, mouse hepatoma Hepa 1-6, rat hepatoma McA RH-7777 and human colon adenocarcinoma LS-174T, and stronger against mouse sarcoma S180-II and mouse leukemia L-1210 cells. The appearance of colloidal Au during the process of hydrolysis under physiological conditions may explains the low cytostatic activity.
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PMID:Structural characterization and cytostatic activity of chlorobischolylglycinatogold(III). 1137 92

Fatty acid conjugation of alcohols, catalyzed by fatty acid ethyl ester synthase (FAEES), results in the formation of lipophilic esters. Although the activity of FAEES is reported in almost all organs, including plasma, the interrelationship among various proteins expressing FAEES activity in different organs/tissues is not well understood. Earlier, we have reported an inhibition of FAEES activity in human hepatoma cells by tri-o-tolylphosphate (TOTP; serine esterase inhibitor). The present study was undertaken to further characterize the hepatic, plasma, and pancreatic FAEES in rats after ip injection of 10, 25, 50, or 100 mg/kg TOTP in corn oil or vehicle alone. After 18 h, animals were euthanized and FAEES activity in the plasma and postnuclear fractions of hepatic and pancreatic homogenates were assayed by measuring the ester formation following incubation with [1-(14)C]oleic acid and ethanol or methanol as substrates. Significant inhibition of FAEES activity was observed in hepatic postnuclear fraction. The esterase activity also showed a pattern similar to fatty acid ethyl and methyl ester synthesizing activity. A trend similar to hepatic synthesizing and hydrolyzing activities was also found in the plasma of TOTP-treated rats. However, no inhibition of synthetic activity toward formation of fatty acid ethyl or methyl esters or p-nitrophenyl acetate hydrolyzing activity was observed in the pancreas of rats after TOTP exposure. Our results also show that the protein expressing FAEES activity in the pancreas does not cross-react with antibodies to rat adipose tissue FAEES using Western blot analysis, which recognizes approximately 60- and approximately 84-kDa proteins in the liver and plasma, respectively. Furthermore, the inhibition in liver is at the functional level of enzyme as no change was observed between control and treated animals by immunohistochemistry. We conclude that fatty acid ethyl or methyl ester synthesizing enzyme(s) in the liver and plasma, which are inhibited by TOTP, are different from that present in the pancreas.
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PMID:Differential inhibition of hepatic, pancreatic, and plasma fatty acid ethyl ester synthase by tri-o-tolylphosphate in rats. 1188 45

A new bicyclic diarylheptanoid, rel-(3S,4aR,10bR)-8-hydroxy-3-(4-hydroxyphenyl)-9-methoxy-4a,5,6,10b-tetrahydro-3H-naphtho[2,1-b]pyran (1), as well as four known compounds, 1,2-dihydro-1,2,3-trihydroxy-9-(4-methoxyphenyl)phenalene (2), hydroxyanigorufone (3), 2-(4-hydroxyphenyl)naphthalic anhydride (4), and 1,7-bis(4-hydroxyphenyl)hepta-4(E),6(E)-dien-3-one (5), were isolated from an ethyl acetate-soluble fraction of the methanol extract of the fruits of Musa x paradisiaca cultivar, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structure and relative stereochemistry of compound 1 were elucidated unambiguously by one- and two-dimensional NMR experiments ((1)H NMR, (13)C NMR, DEPT, COSY, HMQC, HMBC, and NOESY) and single-crystal X-ray diffraction analysis. Isolates 1-5 were evaluated for their potential cancer chemopreventive properties utilizing an in vitro assay to determine quinone reductase induction and a mouse mammary organ culture assay.
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PMID:Constituents of Musa x paradisiaca cultivar with the potential to induce the phase II enzyme, quinone reductase. 1238 Nov 12

Various extracts prepared from stems of Euonymus alatus were tested for cytotoxic activity on human hepatocellular carcinoma cell line, Hep3B cells using the XTT assay method. Also, the extracts were investigated the inhibitory effects on matrix metalloproteinase (MMP)-9 activity using gelatin zymography. The methanol extract, hexane and ethyl acetate fraction exhibited weak cytotoxic activity (IC(50) of >100 microg/ml). However, butanol (IC(50)=65 microg/ml) and chloroform (IC(50)=85 microg/ml) fraction exhibited strongly cytotoxic activity. Gelatin zymography showed that the Hep3B cells secreted matrix metalloproteinase (MMP), probably including MMP-9, which may be involved in tumor cell invasion and metastasis. The butanol fraction showed stronger inhibitory effect of proteolytic activity than other fractions. Also, the butanol fraction was able to decrease the proteolytic activity of MMP-9 in a concentration-dependent manner on zymography. These results suggest that the butanol fraction from E. alatus has highly inhibitory effect on MMP-9 in comparatively low cytotoxicity.
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PMID:Inhibitory effect of methanol extract of Euonymus alatus on matrix metalloproteinase-9. 1257 16

HDL receptor plays a very important role in reverse cholesterol transport, and it represents a novel therapeutic target for atherosclerosis. For construction of an in vitro high-throughput drug screening model based on competitive receptor--ligand binding, the extracellular domain of HDL receptor was expressed in the methylotropic yeast Pichia pastoris. The DNA fragment encoding for extracellular domain of HDL receptor was cloned by RT-PCR from Hepatoma Bel-7402 total RNA and the nucleotide sequence of the cloned cDNA was verified by inserting it into pGEM-T vector. Then the cDNA was subcloned into pPIC9K, the integrative secretory expression plasmid of Pichia pastoris was constructed, with the methanol-inducible alcohol oxidase promoter and alpha-signal peptide. The recombinant plasmid was transformed into Pichia pastoris GS115 (His- strain) by electroporation. PCR was used to confirm the insertion of HDLR gene into the genome of Mut+ transformants. During cultivation the recombinant strain was induced by 1% methanol and supernatant was analyzed by SDS-PAGE and Western blot. The result showed a specific protein band at approximately 64.5 kDa after 5 days of induction. Then the ligand binding activity was confirmed using the DiI-AcLDL as ligand.
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PMID:[Expression of the human extracellular domain of high density lipoprotein receptor in methylotropic yeast]. 1281 71

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


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