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)

The cytotoxicity of the MEIC reference chemicals was investigated in rat hepatoma-derived Fa32 cells. The total protein content was measured as an endpoint after exposure times of 30 min and 24 h, both in normal and glutathione-depleted cells. The neutral red uptake inhibition and the MTT conversion were also measured after 30 min. On average, the cytotoxicity was higher in glutathione-depleted cells when compared to normal cells, and was lower after 30 min than after 24 h. Evidence was obtained for lysosomal attack (of five chemicals) or mitochondrial dysfunction (of six chemicals) as the primary intoxication mechanism. Malathion and mercuric chloride belong to both series of chemicals. Good to excellent correlations were observed when the 50% inhibitory concentrations of the six different in vitro assays were compared. When the six in vitro assays in Fa32 cells were compared with the human toxicity, the correlation coefficient was almost always identical to that obtained previously in human hepatoma-derived Hep G2 cells. The latter was the best acute in vitro assay for the prediction of human toxicity within the MEIC study. Altogether the results integrate very well with the basal cytotoxicity concept (Ekwall, B., 1995. The basal cytotoxicity concept. In: Goldberg, A.M., Van Zutphen, L.F.M. (Eds.), The World Congress on Alternatives and Animal Use in the Life Sciences: Education, Research, Testing. Mary Ann Liebert Publishers, New York, pp. 721-725).
 ...
PMID:Cytotoxicity of the MEIC reference chemicals in rat hepatoma-derived Fa32 cells. 1099 72

Chemotherapy with cytostatic and cytotoxic drugs is the main treatment modality for disseminated cancer. However, despite initial clinical responses seen in certain histotypes, such as small cell lung cancer, relapses mostly occur with chemoresistant phenotypes. In order to prolong the relapse-free period, a combination of chemo- and immunotherapy might offer a new treatment strategy. Here, we have tested our hypothesis that complement activation, induced by monoclonal antibodies, in combination with cytostatic drugs may result in additive cytotoxicity in vitro. Doxorubicin, cisplatinum and etoposide were tested in combination with human complement and a murine monoclonal antibody (MAb F12) directed against the tumor-associated ganglioside antigen fucosyl GM1 on a rat hepatoma (H4-II-E) cell line which was used as tumor model. Using the MTT assay to measure cell survival, supra-additive (i.e. synergistic) cytotoxic effects were seen with each of the cytostatic drugs, the strongest being observed with doxorubicin. These results show promise for further research exploring possible prognostically favorable interactions between cytostatic drugs and monoclonal antibodies in the treatment of cancer.
 ...
PMID:Supra-additive cytotoxic effects of a combination of cytostatic drugs and antibody-induced complement activation on tumor cells in vitro. 1112 82

Howiinol A (GHM-10) is a kind of phenylethylene pyrone compounds isolated from Goniothalamus howii. By using the techniques of cell growth curve determination, MTT test, soft agar colony assay and experimental therapy of transplantable tumors in mice, it is found that GHM-10 exerts potent inhibitory effect on cancer cells but its influence on normal cells is relatively slight; the sensitivity of a drug-resistant cell line, KB/VCR 2000, to GHM-10 is similar to its parent cell line KB. Remarkable therapeutic effect can be seen in mice bearing H22 hepatoma and Lewis lung cancer and in mice with ascetic sarcoma 180 when GHM-10 is orally or intraperitoneally administered. The IC50s of L1210 cells treated with GHM-10 for 1 and 24 h are 6.85 and 3.32 micrograms.ml-1 respectively. The ratio of IC50 1 h and IC50 24 h is only 2.06, indicating that the action of GHM-10 is conformed to a cell cycle non-specific cytotoxic agent. By using trypan blue exclusive test and morphological examination, it is demonstrated that the main effect of GHM-10 is to inhibit the cell proliferation. Flow cytometery technique is used to analyze the cell cycle of L1210 cells. The results show that to some extent, GHM-10 blocks the cell cycle transition from G1 phase to S phase. By using [3H] labeled precursor incorporation technique, it is shown that GHM-10 significantly suppresses the biosynthesis of DNA, RNA and protein in L1210 cells, and the DNA synthesis is mostly affected. At 1 h after the cells were treated with GHM-10, these inhibitory effects have already been irreversible, suggesting that GHM-10 may cause structural damage on DNA molecules. However, GHM-10 is unable to intercalate into DNA molecules or to destroy its structure directly. By using single cell gel electrophoresis and alkaline elution technology, it is confirmed that GHM-10 causes DNA molecule damage and single strand breakage in L1210 cells. Further studies show that GHM-10 markedly inhibits DNA dehelix induced by DNA topoisomerase II both inside and outside the cells, indicating that GHM-10 is acting as an inhibitor of DNA topoisomerase II.
 ...
PMID:Anticancer effect of Howiinol A and its mechanism of action. 1126 Dec 1

The ability of (-)-epicatechin (EC), (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG) to inhibit the growth of HCT 116 colorectal and Hep G2 hepatocellular carcinoma cells was examined by MTT and clonogenic assays (CA). The respective catechins inhibited the growth of HCT 116 more strongly than Hep G2. In MTT assay, IC(50) values of EGC and EGCG against HCT 116 grew smaller on prolongation of the exposure times of the cells to the catechins. In CA, however, these two catechins had IC(50) values ranging between 7.6+/-0.4 and 11.2+/-0.5 microM against the same cells regardless of the exposure times. EC showed much weaker growth inhibitions relative to the two aforementioned catechins.
 ...
PMID:Inhibition of green tea catechins against the growth of cancerous human colon and hepatic epithelial cells. 1144 33

To study the therapeutic effects of herpes simplex virus thymidine kinase (HSV-TK) gene transferred by the EBV-based expression vector (pDR2) on experimental hepatocellular carcinoma, pDR2-TK gene was delivered into human hepatocellular carcinoma cell line SMMC-7721 by using liposome-mediated transfection technique, and then gene expression was detected by RT-PCR, and the killing effects were examined through MTT method. In the nude mice hepatoma model, the antitumor effects of pDR2-TK/GCV system was evaluated in terms of tumor growth. MTT results showed that the pDR2-TK/GCV had cytotoxic effect and about 70% SMMC-7721 cells were killed when GCV was at 1000 mumol/L. In vivo experiment showed that the tumor size in nude mice with transferred pDR2-TK gene was significantly smaller than that in control group (P < 0.01). On the 10th day the tumor in 3 mice (60%) disappeared completely after GCV treatment. It is concluded that the pDR2-TK/GCV system has marked killing effects on the experimental hepatocellular carcinoma.
 ...
PMID:Gene therapy of HSV-TK transferred by the EBV based expression vector on experimental hepatocellular carcinoma. 1152 15

Human primary hepatocellular carcinoma (HCC)is one of the highly prevalent malignant diseases worldwide, the identification of HCC-associated genes has been a major approach in elucidating the molecular mechanism of tumorigenesis of HCC. In our previous studies, a function-unknown gene, which displayed marked expression difference between the HCC sample and normal liver control has been detected by cDNA microarray. This gene was named after fup1 (function-unknown protein 1), and was cloned according to the data of GenBank. The cDNA of fup1 has an open-reading frame 1233 base pairs in size. Here, the function analysis of FUP1 related to HCC is being reported. The NIH3T3 cells transiently transfected with FLAG-conjugated FUP1 revealed strong nuclear staining in immunofluorescent assay. Furthermore, cell proliferation enhancing activity of fup1 was shown by MTT assay in stable transfectant NIH3T3 cell line with pcDNA3-derived plasmid having fup1 under the regulation of pCMV, while cell proliferation repressing activity of antisense fup1 was observed in BEL7404 stable transfectant cells. Tumorigenicity of the above stable transfectant cells was analyzed in nude mice compared with appropriate controls. The result was in good agreement with MTT assay. Elevated tumorigenicity of fup1 transfected NIH3T3 cell and repressed tumorigenicity of antisense fup1 transfected BEL7404 cell were clearly demonstrated. The results above suggested that fup1 might be a critical gene related to carcinogenesis of HCC. Detailed molecular function of fup1 remains to be elucidated.
 ...
PMID:FUP1, a gene associated with hepatocellular carcinoma, stimulates NIH3T3 cell proliferation and tumor formation in nude mice. 1152 4

The field of genomics has great potential in toxicology; however, the technology is still in its infancy and there are many questions that need to be addressed. In this study we focus on the use of toxicogenomics for the determination of gene expression changes associated with hepatotoxicity. The human hepatoma cell line HepG2 was used to assess the toxic effects of two well-studied hepatotoxins, carbon tetrachloride (CCl(4)) and ethanol (EtOH). Replicate dishes of HepG2 cells were exposed to two concentrations of CCl(4) and EtOH--doses which caused 20% and 50% cell death (as determined by the MTT assay) were chosen [0.18% and 0.4% (v/v) CCl(4); 2.5% and 5% (v/v) EtOH] and the cells exposed for periods of 2 and 24 h. mRNA was extracted and used to probe Atlas Human Toxicology II arrays (Clontech). Preliminary data revealed that following a 2-h exposure at the low doses of both compounds, few changes in gene expression were detected. However, after 24-h exposure of the cells to the same low concentration of both compounds, multiple changes in gene expression were observed, many of which were specific to the individual hepatotoxins, presumably reflecting their different mechanisms of action. CCl(4) treatment of HepG2 cells gave rise to treatment specific up-regulation of genes involved in extracellular transport and cell signalling, whereas EtOH treatment gave rise predominantly to down-regulation of genes involved in stress response and metabolism. In addition, changes in regulation of certain genes (involved in stress response and cell cycle) were common to both treatments. Exposure of HepG2 cells to higher doses of the hepatotoxins gave rise to more changes in gene expression at lower exposure times. These results strongly suggest that different mechanisms of hepatotoxicity may be associated with specific patterns of gene expression, while some genes associated with common cellular responses may be useful as early markers of toxicity.
 ...
PMID:The use of genomics technology to investigate gene expression changes in cultured human liver cells. 1156 70

Antibiotic G0069A, produced by a Streptomyces strain isolated from a soil sample collected in Yunnan Province, China, has been verified as a clavam peptide. Determined by MTT assay, G0069A showed highly potent cytotoxicity to cancer cells with multidrug resistance. The IC50 values of G0069A to KB and KB/VCR cells were 0.60 and 0.46 mumol.L-1, and to MCF-7 and MCF-7/ADM cells were 1.4 and 1.2 mumol.L-1, respectively. G0069A displayed equally potent cytotoxicity to the parent cell lines and their resistant sublines. When administered by i.v. or i.p. route at tolerable doses, G0069A exhibited markedly inhibitory effect on the growth of sarcoma 180 and hepatoma 22 in mice. At dose level of 3 mg.kg-1, i.v., x3, sarcoma 180 and hepatoma 22 were suppressed by 87%(P < 0.01) and 72%(P < 0.01), respectively. The results indicate that G0069A is a beta-lactam antibiotic showing antitumor activity.
 ...
PMID:[Antitumor activity of the clavam peptide antibiotic G0069A]. 1159 87

Hepatitis and fulminant hepatic failure have, infrequently, been associated with nimesulide. To establish if nimesulide or its analogues have direct cytotoxic activity on liver cells, experiments were undertaken to investigate the effects of nimesulide and its principal metabolites and production intermediates on the viability and growth of the human hepatoma cell line, HepG2, in vitro. The parent drug, metabolites or production intermediates as well as formulations of nimesulide were incubated for 6-48 hr with HepG2 cells and the extent of toxicity determined using the mitochondrial selective redox dye 3-4,5-dimethylthazol-2-yl)-2,4-diphenyl tetrazolium bromide (MTT). The results showed that there was no appreciable cytotoxic activity exhibited by nimesulide and its principle metabolites or production intermediates on HepG2 cells.
 ...
PMID:Effects of nimesulide and its metabolites or manufacturing intermediates on the viability and growth of the human hepatoma HepG2 cell line. 1175 24

The objective of the present study was to investigate the multicellular resistance of human hepatocarcinoma cells BEL-7402 to pharmorubicin. Cells (1 x 10(4)) and 200 microcarrier Cytodex-3 beads were seeded onto a 24-well plate and cultured in RPMI 1640 medium. After the formation of multicellular aggregates, morphology and cell viability were analyzed by scanning electron microscopy, transmission electron microscopy and flow cytometry, respectively. The IC50 was determined by flow cytometry and MTT assay after the cells cultured in aggregates and monolayers were treated with pharmorubicin. The culture products exhibited structural characteristics somewhat similar to those of trabecular hepatocarcinoma in vivo. Among the microcarriers, cells were organized into several layers. Intercellular spaces were 0.5-2.0 microm wide and filled with many microvilli. The percent of viable cells was 87%. The cells cultured as multicellular aggregates were resistant to pharmorubicin with IC50 4.5-fold and 7.7-fold that of monolayer culture as determined by flow cytometry and MTT assay, respectively. This three-dimensional culture model may be used to investigate the mechanisms of multicellular drug resistance of hepatocarcinoma and to screen new anticancer drugs.
 ...
PMID:Resistance of multicellular aggregates to pharmorubicin observed in human hepatocarcinoma cells. 1184 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>