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)

Cadmium telluride (CdTe) nanoparticles exhibit strong and stable fluorescence that is attractive for many applications such as biological probing and solid state lighting. The evaluation of nanoparticle toxicity is important for realizing these practical applications. However, no systematic studies of CdTe nanoparticle toxicity have been reported. We investigated and compared the size- and concentration-dependent cytotoxicity of CdTe nanoparticles in human hepatoma HepG2 cells using the MTT assay. CdTe nanoparticles elicited cytotoxicity in a concentration- and size-dependent manner, with smaller-sized particles exhibiting somewhat higher potency. Lesser cytotoxicity of partially purified CdTe-Red particles (following methanol precipitation and resuspension) suggested that free cadmium ions may contribute to cytotoxicity. We also evaluated the acute toxicity of CdTe-Red particles following intravenous exposure in male rats (2 micromol/kg). Few signs of functional toxicity or clinical (urinary or blood) changes were noted. Interestingly, motor activity was transiently reduced (2 hours after treatment) and then significantly increased at a later timepoint (24 hours after dosing). These studies provide a framework for further characterizing the in vitro and in vivo toxic potential of different types of CdTe nanoparticles and suggest that the nervous system may be targeted by these nanoparticles under some conditions.
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PMID:In vitro and in vivo toxicity of CdTe nanoparticles. 1745 Jul 85

The subject of the study was the unidentified protein Ag A2/3, which is found in some cells of rat hepatoma McA RH7777 and their clones. The feature of this protein is that its expression is alternative to alfa-fetoprotein (AFP), i.e. Ag A2/3 is not found in cells and cell clones containing AFP, and vice versa. Ag A2/3 proved to be a cell stress protein--it was induced by heavy metal salts (Pb2+ and Cd2+) in the liver of adult rats and AFP+/A2/3(-) clones of hepatomas; the attenuation of AFP synthesis occurred simultaneously. This paper describes the preparation of Ag A2/3 for sequence analysis, and the scheme of Ag A2/3 purification. When trying to obtain a blot for sequencing it proved to be impossible to reveal the protein using McAb to Ag A2/3 after the transfer of separated proteins on PVDF. The reactivity of the antigen determinant was reestablished with blot processing on PVDF membrane with methanol and Twin 80.
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PMID:[The purification of the protein alternative to alfa-fetoprotein]. 1808 30

Cytochrome P4501A (CYP1A) induction was evaluated in the rat hepatoma cell line H4IIE as a biomarker of exposure to organic compounds. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide assay was performed to assess the viability of cells exposed to environmentally relevant concentrations of cadmium. Cadmium concentrations greater than approximately 0.7 microM were found to affect cell viability. Cells were exposed to environmentally relevant concentrations of 3,3',4,4'-tetrachlorobiphenyl (PCB 77) or benzo[a]pyrene (BaP) and to combinations of PCB 77, BaP, and cadmium based on a statistical experimental design. Quantification of CYP1A proteins using Western blot analysis showed that both BaP and PCB 77 induced CYP1A in a concentration-dependent manner up to 5 microM. Response surface modeling for evaluation of the combined effect of compounds was conducted using the multivariate regression model projection to latent structures (PLS). Analysis of response surface models for the ternary mixtures indicated antagonistic interactions between BaP and PCB 77 and a possible inhibitory effect of cadmium on PCB 77- induced CYP1A. Use of CYP1A induction in the H4IIE cell line with immunodetection of CYP1A proteins, combined with the application of response surface design and PLS, is shown to be a suitable strategy for evaluating combined effects in pollutant mixtures.
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PMID:Application of statistical experimental design and multivariate data analysis for evaluation of mixtures using cytochrome P4501A induction. 1831 70

Carcinogenesis is an important chronic toxicity of metals and metalloids, although their mechanisms of action are still unclear. Comparison of gene expression patterns induced by carcinogenic metals, metalloids, and model carcinogens would give an insight into understanding of their carcinogenic mechanisms. In this study, we examined the gene expression alteration in human hepatoma cell line, HepG2, after exposing to two metals (cadmium and nickel), a metalloid (arsenic), and three model carcinogenic chemicals N-dimethylnitrosoamine (DMN), 12-O-tetradecanoylphorbol-13-acetate (TPA), and tetrachloroethylene (TCE) using DNA microarrays with 8,795 human genes. Of the genes altered by As, Cd, and Ni exposures, 31-55% were overlapped with those altered by three model carcinogenic chemical exposures in our experiments. In particular, the metals and metalloid shared certain characteristics with TPA and TCE in remarkable upregulations of the genes associated with progression of cell cycle, which might play a central role in As, Cd, and Ni carcinogenesis. This characteristic of gene expression alteration was partially counteracted by intracellular accumulation of vitamin C in As-exposed cells, whereas the number of cell-cycle associated genes was increased in Cd- and Ni-exposed cells. In our experimental conditions, ROS might have an accelerative effect on the cell proliferation mechanisms of As, but have an inhibitory effect on those of other two heavy metals. Furthermore, based on the results of Q-PCR, the oncogene PTTG1, which was upregulated by all carcinogenic chemical exposures in the array experiments, might be a useful biomarker for evaluation of the carcinogenesis of inorganic carcinogens.
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PMID:Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal carcinogenesis. 1903 21

Xenobiotics, including heavy metals, exist in nature as complex mixtures of compounds with possible interactions. Induction of DNA damage such as DNA strand breaks may exert detrimental consequences to both individuals and populations. In this study, the induction of DNA double-strand breaks was assessed using the H4IIE rat hepatoma cell line following exposure to high and environmentally relevant concentrations of chloride salts of the metals cadmium (Cd), copper (Cu), and zinc (Zn), both singly and in combination. DNA strand break analysis was performed using agarose gel electrophoresis. Median molecular lengths were calculated from fragment size distributions acquired from gel image data and were used as a quantitative measure of DNA double-strand break induction. Exposure to high concentrations of Cu and Cd in combination produced a significant increase in the occurrence of DNA strand break. However, exposing cells to high concentrations of Cu, Cd, and Zn in combination resulted in significantly lower DNA double-strand break compared to control cells. Addition of low Zn to the Cd/Cu mixture restored DNA damage level back to that of the control. Environmentally relevant concentrations of Cd, Cu, and Zn did not appear to induce DNA strand breaks in the H4IIE cell line.
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PMID:Induction of DNA double-strand breaks in the H4IIE cell line exposed to environmentally relevant concentrations of copper, cadmium, and zinc, singly and in combinations. 1918 30

Recent advances and progress in nanobiotechnology have demonstrated many nanoparticles (NPs) as potential and novel drug delivery vehicles, therapeutic agents, and contrast agents and luminescent biological labels for bioimaging. The emergence of new biomedical applications based on NPs signifies the need to understand, compare, and manage their cytotoxicity. In this study, we demonstrated the use of high-content screening assay (HCA) as a universal tool to probe the cytotoxicity of NPs and specifically cadmium telluride quantum dots (CdTe QDs) and gold NPs (Au NPs) in NG108-15 murine neuroblastoma cells and HepG2 human hepatocellular carcinoma cells. Neural cells represent special interest for NP-induced cytotoxicity because the optical and electrical functionalities of materials necessary for neural imaging and interfacing are matched well with the properties of many NPs. In addition, the cellular morphology of neurons is particularly suitable for automated high content screening. HepG2 cells represent a good model for high content screening studies since they are commonly used as a surrogate for human hepatocytes in pharmaceutical studies. We found the CdTe QDs to induce primarily apoptotic response in a time- and dosage-dependent manner and produce different toxicological profiles and responses in undifferentiated and differentiated neural cells. Au NPs were found to inhibit the proliferation and intracellular calcium release of HepG2 cells.
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PMID:High-content screening as a universal tool for fingerprinting of cytotoxicity of nanoparticles. 1920 90

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), considered as endocrine disruptors, tend to accumulate in fatty tissues. Dioxin-responsive element chemical activated luciferase gene expression assay (DRE-luciferase assay) has been recognized as a semi-quantitative method for screening dioxins for its fast and low-cost as compared with HRGC/HRMS. However, some problems with the bioassay, including specificity, detection variation resulted from different cleanup strategies, and uncertainty of false-negative or false-positive results, remain to be overcome. Cadmium is a prevalent environmental contaminant around the world. This study was aimed to examine the effects of cadmium on the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of aryl hydrocarbon receptor (AhR)-mediated gene expression in human hepatoma cells (Huh7-DRE-Luc cells and Huh7 cells). Ethoxyresorufin-O-deethylase (EROD) and DRE-luciferase assay were employed to determine the enzyme activity of cytochrome P450 1A1 (CYP1A1) and activation of AhR, respectively. The results showed that Cd(2+) levels significantly inhibited the induction of TCDD-induced CYP1A1 and DRE luciferase activation in hepatoma cells. The 50% inhibited concentrations (IC(50)) of CdCl(2) were 0.414 microM (95% confidence interval (C.I.): 0.230-0.602 microM) in Huh7-DRE-Luc cells and 23.2 microM (95% C.I.: 21.7-25.4 microM) in Huh7 cells. Accordingly, prevention of interference with non-dioxin-like compounds in a DRE-luciferase assay is of great importance in an extensive cleanup procedure.
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PMID:The inhibition effect of 2,3,7,8-tetrachlorinated dibenzo-p-dioxin-induced aryl hydrocarbon receptor activation in human hepatoma cells with the treatment of cadmium chloride. 1947 68

Cadmium, mercury and rotenone are environmental pollutants whose neurotoxic mechanisms are not fully understood. We have shown previously that exposure of nerve cells to these agents produces oxidative stress which reversibly blocks growth factor and cytokine-mediated Janus kinase (Jak)/signal transducer and activator of transcription (STAT) signaling. Here we determined a critical role for mitochondrial dysfunction in inhibiting Jak/STAT activity in human BE(2)-C neuroblastoma cells. Exposure of BE(2)-C cells to the heavy metals CdCl(2) and HgCl(2) and to the mitochondrial complex I inhibitor rotenone inhibited interleukin-6, interferon-gamma and ciliary neurotrophic factor-mediated Jak/STAT signaling, reduced Jak1 and Jak2 auto-phosphorylation and induced Jak tyrosine nitration. However, identical exposure of HepG2 hepatoma cells produced no inhibition of these cytokine responses. In contrast, mitochondria in both BE(2)-C and HepG2 cells showed reduced mitochondrial membrane potential and increased superoxide production after exposure to CdCl(2), HgCl(2) and rotenone. Further, in an in vitro Jak auto-phosphorylation assay Jak2 isolated from either BE(2)-C or HepG2 cells was equally inhibited by mitochondria made dysfunctional by treatment with CdCl(2), HgCl(2) and rotenone. Each of these pro-oxidant effects was reversed by the mitochondrial antioxidant alpha-lipoic acid. The actions of cadmium were also blocked by the mitochondrial complex III bypass agent, 2,6-dichloroindophenol. Therefore, in BE(2)-C cells CdCl(2), HgCl(2) and rotenone disrupt mitochondria to increase intracellular ROS, which directly inhibits neuronal Jak tyrosine kinase activity. Non-neuronal cells such as HepG2 cells that are resistant to oxidative stress-mediated inhibition of cytokine signaling possess some as yet unknown mechanism that protects Jak kinases from oxidative insults. Pro-oxidant-induced mitochondrial dysfunction resulting in selective neuronal Jak inhibition provides a potential mechanism for environmental agents to promote neurodegeneration.
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PMID:Environmental toxicants inhibit neuronal Jak tyrosine kinase by mitochondrial disruption. 1963 91

The application of quantum dots (QDs) in various biomedical areas requires detailed studies of their toxicity. We report a new strategy for probing the biocompatibility of these nanocrystals, namely, a dynamic investigation of cellular uptake images, cell growth curves, metabolic activity changes, and apoptosis aspects of cadmium telluride QDs capped with cysteamine (Cys-CdTe QDs) on human hepatocellular carcinoma SMMC-7721 cells. We used a real-time cell electronic sensing (RT-CES) system in combination with fluorescence microscopy, 3-(4,5-dimethyl-thiazol-zyl)-2,5-diphenyltetrazolium bromide assay, and flow cytometry (FCM) analysis. As observed from fluorescence images and RT-CES system results, Cys-CdTe QDs can readily bind on the cell plasma membrane and then enter into the cancer cell, causing decreased adherence of cancer cells during the initial 6-12 h, while the metabolic activity apparently decreased. After 24 h, the metabolic activity of the cancer cells was significantly reduced, with continued reduction in metabolic activity observed at even longer incubation times. Moreover, FCM observation and DNA fragmentation analysis clearly indicate apoptosis-related phenomena when SMMC-7721 cells were treated with the Cys-CdTe QDs. Thus, our study reveals details of the cellular aging and death process induced by Cys-CdTe QDs.
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PMID:Probing the dynamic effect of cys-CdTe quantum dots toward cancer cells in vitro. 1996 Dec 3

The free H(2)xspa ligands [xspa = pspa, Clpspa, tspa or fspa where p = 3-(phenyl), Clp = 3-(2-chlorophenyl), t = 3-(2-thienyl), f = 3-(2-furyl) and spa = 2-sulfanylpropenoato], their Zn(II) complexes of formula [HQ](2)[Zn(xspa)(2)] (HQ = diisopropylammonium) and the Cd(II) equivalents were prepared and characterized by elemental analysis and by IR, Raman and NMR ((1)H, (13)C) spectroscopy. X-Ray studies of the crystal structures of [HQ](2)[Zn(pspa)(2)], [HQ](2)[Zn(Clpspa)(2)], [HQ](2)[Zn(tspa)(2)] and [HQ](2)[Zn(fspa)(2)] show that the zinc atom is coordinated to two O atoms and two S atoms of the ligands in a distorted tetrahedral ZnO(2)S(2) environment. In the structures of [HQ](2)[Cd(pspa)(2)] and [HQ](2)[Cd(Clpspa)(2)] the cadmium atom is coordinated to three S atoms and two carboxylato O atoms of the ligands in a distorted trigonal bipyramidal environment. The interchange of ligands between Zn(II) and Cd(II) was studied by (113)Cd NMR spectroscopy. The in vitro protective effect of H(2)xspa and their Zn(II) complexes against Cd toxicity was investigated using the human hepatocarcinoma HepG2 cell line and the pig renal proximal tubule LLC-PK1 cell line. The incorporation of Zn(II) was found to be relevant in the case of H(2)pspa, with an increase observed in the cell viability of the LCC-PK1 cells with respect to the value for the free ligand.
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PMID:Chemical and in vitro study of the potential of 3-(aryl)-2-sulfanylpropenoic acids and their Zn(II) complexes as protective agents against cadmium toxicity. 2037 18

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