Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three chlorinated methanes, carbon tetrachloride, chloroform, and methylene chloride, known to cause liver tumors in rodents, were given by oral gavage to adult female rats both 21 h and 4 h before sacrifice. Then hepatic DNA damage, ornithine decarboxylase (ODC), cytochrome P-450, glutathione content, and serum alanine aminotransferase (SGPT) activity assays were performed. Carbon tetrachloride increased rat hepatic ODC activity and decreased cytochrome P-450 content at doses both below and above cytotoxicity (as measured by increased SGPT activity). At 54 and 160 mg/kg, chloroform increased hepatic ODC activity with minimal or no elevation in SGPT activity. At 480 mg/kg chloroform increased hepatic ODC and SGPT activity. A dose of 1,275 mg/kg methylene chloride caused a small, but significant amount of hepatic DNA damage. When these three compounds are compared on either an equimolar or equitoxic (1/5 LD50) basis, their ability to induce hepatic ODC or increase SGPT activity was carbon tetrachloride greater than chloroform greater than methylene chloride. The results of this biochemical study are interpreted with respect to the ability of chemicals to cause hepatic cancer by either genetic or epigenetic mechanisms.
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PMID:Biochemical effects of three carcinogenic chlorinated methanes in rat liver. 256 70

Organochlorine pesticides increase the incidence of liver cancer through a multistage process involving tumor promotion. Mirex, an organochlorine pesticide has been shown to be a tumor promoter in mouse skin. In the present study, the effects of methoxychlor, a commonly used organochlorine pesticide, on the development of papillomas in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin and induction of mouse epidermal ornithine decarboxylase (ODC) activity were investigated and compared with 12-O-tetradecanoylphorbol-13-acetate (TPA), a well-known tumor promoter. Methoxychlor neither caused tumor development nor induced epidermal ODC activity. However, TPA resulted in 100% tumor incidence and 8.8 tumors per mouse after 20 weeks of promotion, and induced epidermal ODC activity.
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PMID:Effects of methoxychlor on skin tumor development. 787 47

Arsenicals are epidemiologically significant chemicals in relation to induction of liver cancer in man. In the present study, we investigated the dose-dependent promotion potential of dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenicals in mammals, in a rat liver carcinogenesis model. In experiment 1, glutathione-S-transferase placental form (GST-P)-positive foci, putative preneoplastic lesions, were employed as endpoints of a liver medium-term bioassay for carcinogens (Ito test). Starting 2 weeks after initiation with diethylnitrosamine, male F344 rats were treated with 0, 25, 50 or 100 ppm of DMAA in the drinking water for 6 weeks. All animals underwent two-thirds partial hepatectomy at week 3 after initiation. Examination of liver sections after termination at 8 weeks revealed dose-dependent increases in the numbers and areas of GST-P-positive foci in DMAA-treated rats as compared with controls. In experiment 2, ornithine decarboxylase activity, which is a biomarker of cell proliferation, was found to be significantly increased in the livers of rats treated with DMAA. In experiment 3, formation of 8-hydroxydeoxyguanosine, which is a marker of oxygen radical-mediated DNA damage, was significantly increased after administration of DMAA. These results indicate that DMAA has the potential to promote rat liver carcinogenesis, possibly via a mechanism involving stimulation of cell proliferation and DNA damage caused by oxygen radicals.
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PMID:Promotion of rat hepatocarcinogenesis by dimethylarsinic acid: association with elevated ornithine decarboxylase activity and formation of 8-hydroxydeoxyguanosine in the liver. 947 32

Liver organogenesis and cancerogenesis share common mechanisms. HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Less is known about the involvement of HOX genes with liver cancerogenesis. The comparison of the HOX gene network expression between nontumorous livers and hepatocellular carcinomas (HCCs) highlights significant differences in the locus A HOX genes, located on chromosome 7, with a consistent overexpression of HOXA13 mRNA thus validating this gene deregulation as a feature of HCC. HOXA13 is a determinant of gut primordia and posterior body structures. Transcriptome analysis of HCC/nontumorous liver mRNAs, selected on the basis of HOXA13 overexpression, recognizes a set of deregulated genes. The matching of these genes with previously reported HCC transcriptome analysis identifies cell-cycle and nuclear pore-related HCC phenotype displaying poor prognosis. HOXA13 and HOXA7 homeoproteins share a consensus sequence that physically links eIF4E nuclear bodies acting on the export of specific mRNAs (c-myc, FGF-2, vascular endothelial growth factor (VEGF), ornithine decarboxylase (ODC) and cyclin D1). We report the protein-protein interaction between HOXA13 and eIF4E in liver cancer cells and the deregulation of eIF4E mRNA and protein in cell cycle/nuclear pore HCC group phenotype and in T4 stage HCCs, respectively. Thus, transcriptional and post-transcriptional HOXA13 deregulation is involved in HCC possibly through the mRNA nuclear export of eIF4E-dependent transcripts.
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PMID:The HOX gene network in hepatocellular carcinoma. 2162 5

In the present study, we have evaluated the chemopreventive effects of perillyl alcohol (POH) against diethylnitrosamine-initiated and 2-AAF (2-acetylaminofluorine)-promoted hepatocarcinogenesis in Wistar rats. Efficacy of POH against 2-AAF-induced hepatotoxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, histopathological changes and expression levels of proliferative markers. 2-AAF is a potent hepatotoxicant and a hepatic carcinogen that induces its effect by causing oxidative stress. Pre-treatment of POH prevented oxidative stress and tumour incidences. POH suppressed 2-AAF-induced early tumour markers, namely ornithine decarboxylase activity, thymidine phosphorylase and proliferating cell nuclear antigen (PCNA) protein and also suppressed the expression of pro-apoptotic protein P53. Histopathological findings revealed that POH-pretreated groups showed marked recovery. From our results, it could be concluded that POH markedly protects against chemically induced liver cancer and acts possibly by virtue of its antioxidant and antiproliferative activities.
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PMID:Perillyl alcohol as a protective modulator against rat hepatocarcinogenesis via amelioration of oxidative damage and cell proliferation. 2353 16

Methionine adenosyltransferase (MAT) is an essential enzyme that is responsible for the biosynthesis of S-adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines. MAT1A is expressed in normal liver and MAT2A is expressed in all extrahepatic tissues. MAT2A expression is increased in human colon cancer and in colon cancer cells treated with mitogens, whereas silencing MAT2A resulted in apoptosis. The aim of the current work was to examine the mechanism responsible for MAT2A-dependent growth and apoptosis. We found that in RKO (human adenocarcinoma cell line) cells, MAT2A siRNA treatment lowered cellular SAMe and putrescine levels by 70-75%, increased apoptosis and inhibited growth. Putrescine supplementation blunted significantly MAT2A siRNA-induced apoptosis and growth suppression. Putrescine treatment (100pmol/L) raised MAT2A mRNA level to 4.3-fold of control, increased the expression of c-Jun and c-Fos and binding to an AP-1 site in the human MAT2A promoter and the promoter activity. In human colon cancer specimens, the expression levels of MAT2A, ornithine decarboxylase (ODC), c-Jun and c-Fos are all elevated as compared to adjacent non-tumorous tissues. Overexpression of ODC in RKO cells also raised MAT2A mRNA level and MAT2A promoter activity. ODC and MAT2A are also overexpressed in liver cancer and consistently, similar MAT2A-ODC-putrescine interactions and effects on growth and apoptosis were observed in HepG2 cells. In conclusion, there is a crosstalk between polyamines and MAT2A. Increased MAT2A expression provides more SAMe for polyamines biosynthesis; increased polyamine (putrescine in this case) can activate MAT2A at the transcriptional level. This along with increased ODC expression in cancer all feed forward to further enhance the proliferative capacity of the cancer cell.
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PMID:Polyamine and methionine adenosyltransferase 2A crosstalk in human colon and liver cancer. 2358 7