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)

Mouse mammary tumor virus (MMTV) DNA fragments were cloned into M13 bacteriophage, and the single-stranded recombinant phage DNAs were used as strand-specific nucleic acid hybridization probes to measure synthesis of plus (genomic) and minus strands of MMTV RNA in cultured cell lines and in cell-free preparations of nuclei. Pulse-labeling studies showed that synthesis of MMTV RNA in three different cell lines was highly asymmetric. In nuclear preparations from a cloned line of MMTV-infected rat hepatoma cells, elongation of nascent MMTV RNA chains and initiation of new MMTV RNA chains with nucleoside (beta-S)triphosphates were also highly asymmetric.
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PMID:Asymmetric transcription of mouse mammary tumor virus genes in vivo and in vitro. 632

FU-O-G, the O-glucuronide methylester of 5-fluorouracil (5-FU), is a compound with a unique chemical structure. It is an antitumor agent of the prodrug type which exerts its activity by enzymatically liberating 5-FU in tumor tissues. It has been reported that the antitumor activity of this compound is superior to those of 5-FU and Tegafur (FT-207) in the treatment of various transplantable tumors. In this study, long-term administration of FU-O-G to mice bearing relatively slow-growing tumors such as Lewis lung carcinoma, mammary tumor FM3 A and hepatoma MH-134 was carried out. Consequently, FU-O-G was shown to be remarkably effective against those tumors, whereas 5-FU and FT-207 were hardly effective. Long-term daily administration was shown to be more effective than intermittent dosage in the treatment of Lewis lung carcinoma. In combination therapies of FU-O-G with other antitumor drugs, FU-O-G exhibited a synergistic effect against Lewis lung carcinoma when combined with Carboquone (CQ) or Nimustine hydrochloride (ACNU).
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PMID:[Antitumor effect of FU-O-G, new antitumor agent, following long term administration]. 643 7

Sodium nitrate was given to male noninbred Wistar rats at levels of 800 ppm and 1,600 ppm in a pellet diet for 646 experimental days. The first tum or was found on day 441 in the liver of a rat given a diet containing 800 ppm sodium nitrite. On day 646, liver tumors were found in 1 of 22 rats (4.5%) on an 800-ppm sodium nitrite diet and in 5 of 19 rats (26.3%) on a 1,600-ppm sodium nitrite diet. The incidence of liver tumors in the rats fed 1,600 ppm sodium nitrite was significantly different from that in controls as judged by the t-test (P < 0.05). A hepatocellular carcinoma and a hemangioendothelial sarcoma of the liver were found on day 646 in 2 rats fed 1,600 ppm sodium nitrite. One mammary tumor but no liver tumors were found in the 19 control rats. The concentration of sodium nitrite decreased after preparation of the pellet diet, but it was still at least 70% of the initial amount when the pellets were given to the rats. Volatile N-nitroso compounds, especially dimehylnitrosamine, at ppm levels were detected in the pellet diet with a gas chromatography-thermal energy analyzer.
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PMID:Induction of liver tumors in Wistar rats by sodium nitrite given in pellet diet. 693 Dec 59

The objective of this study was to investigate the induction of liver tumors by arylhydroxamic acids. The potential involvement of sulfate conjugation was minimized by the administration of a N-hydroxy-4-acylaminobiphenyl to female CD rats. This experimental design provided for the exposure of a target organ that has only a low capacity for activation of hydroxamic acids by sulfate conjugation, with a carcinogen that does not induce tumors in liver that possess a high sulfotransferase activity. A single dose of the N-formyl or N-acetyl derivatives of N-hydroxy-4-aminobiphenyl was given i.p. at 0.4 mmol/kg body weight to 34-day-old animals. In attempts to amplify the hepatocarcinogenic potential of the compounds, partial hepatectomy 24 hr before the chemical injection and subsequent long-term treatment with phenobarbital in the diet were carried out. For comparative purposes, other animals were subjected to three additional partial hepatectomies subsequent to the carcinogen administration instead of the phenobarbital treatment. The experiments were terminated 64 weeks after injection. Both the N-formyl and N-acetyl derivatives of N-hydroxy-4-aminobiphenyl, in conjunction with partial hepatectomy and subsequent treatment of dietary phenobarbital, induced a high incidence of neoplastic nodules and gamma-glutamyltranspeptidase-positive foci in the liver. Only one hepatocellular carcinoma was observed in each treatment group. Repeated partial hepatectomies enhanced the yield of gamma-glutamyltranspeptidase-positive foci but were ineffective in producing neoplastic nodules. In addition to the liver lesions, mammary tumors were also induced. Importantly, an inhibitory effect of the subsequent administration of phenobarbital was observed on mammary tumor formation, possibly because of alterations in hormone metabolism resulting from the induction of microsomal enzymes by phenobarbital, which resulted in a decreased promoting effect. There was no difference in the tumorigenicity of the formyl and acetyl derivatives in these experiments.
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PMID:Effects of partial hepatectomy and dietary phenobarbital on liver and mammary tumorigenesis by two N-hydroxy-N-acylaminobiphenyls in female CD rats. 723 40

A newly synthesized mycophenolic acid (MPA) derivative, ethyl O-[N-(p-carboxyphenyl)-carbamoyl]-mycophenolate (CAM, NSC-297879D) was tested for antitumor activity, when given orally, against transplantable murine tumors. The compound was markedly effective against transplantable murine tumors. The compound was markedly effective against leukemia P388 and L1210, lymphoma L5178Y, mastocytoma P815 and sarcoma Meth-A, moderately effective against sarcoma-180, C3MC2 and BAMC1, Ehrlich carcinoma, Lewis lung carcinoma and melanoma B16 and marginally effective against hepatoma MH134. The antitumor effects were manifested not only in growth inhibitory effects on subcutaneously transplanted tumors but also in the prolongation of life span of mice int which the tumors had been inoculated intraperitoneally or subcutaneously. The growth of primary transplants of a mammary tumor which developed spontaneously in a C3H/He mouse was inhibited by consecutive administration of CAM frm the 34th day after the transplantation. Oral CAM was more potent than its mother compound, MPA, in the tumor models examined. These results indicate that orally administered CAM has a wide antitumor spectrum.
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PMID:Antitumor activity of a new compound, ethyl O-[N-(p-carboxyphenyl)-carbamoyl]-mycophenolate, against various experimental tumors upon oral administration. 727 50

Rat hepatoma H4IIE and mouse hepatoma Hepa 1c1c7 cells were transiently transfected with a plasmid construct that contained the bacterial chloramphenicol acetyltransferase (CAT) gene under the control of the mouse mammary tumor virus promoter and one copy of the dioxin responsive element. Treatment of transfected H4IIE and Hepa 1c1c7 cells with 10(-13) to 10(-6) M 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a concentration-dependent increase in transient CAT activity. Maximum CAT activity was induced in both cell lines by exposure to 10(-9) M TCDD. The induction of CAT activity correlated well with the TCDD-induced, P4501A1-dependent ethoxyresorufin O-deethylase activity. Cotreatment of transfected cells with 10(-9) M TCDD and 10(-8) to 10(-6) M alpha-naphthoflavone (alpha NF) or 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) resulted in a concentration-dependent reduction of TCDD-induced CAT activity. Treatment of cells with 10(-6) M alpha NF or MCDF alone resulted in only minimal induction of CAT activity. Both antagonists inhibited the induction of genes under the control of the CYP1A1 and mouse mammary tumor virus promoters, which indicates that the alpha NF- and MCDF-mediated antagonism of TCDD-induced, aryl hydrocarbon receptor-dependent gene transcription does not depend on promoter context.
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PMID:In vitro inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced activity by alpha-naphthoflavone and 6-methyl-1,3,8-trichlorodibenzofuran using an aryl hydrocarbon (Ah)-responsive construct. 766 69

The phosphoenolpyruvate carboxykinase (PEPCK) gene is regulated at the transcriptional level by a variety of effectors in a tissue-specific fashion. In order to study the parameters involved in the tissue-specific hormonal regulation of the PEPCK gene, we have used a transient expression test in well-differentiated rat hepatoma cells as well as in dedifferentiated variants. In this test, the PEPCK promoter is induced by glucocorticoids in well-differentiated FGC4 cells, but not in H5 dedifferentiated variants, in spite of the presence in H5 cells of the glucocorticoid receptor. Study of the PEPCK promoter using electrophoretic mobility shift assays reveals binding sites for the liver-enriched transcription factors HNF1, vHNF1, HNF3, HNF4, and CAAT/enhancer binding protein members. Overexpression of the liver-enriched transcription factors absent in the dedifferentiated variants, such as HNF1 and HNF4, is not sufficient to restore glucocorticoid response of the PEPCK promoter in the variants. Moreover, systematic analysis of the PEPCK promoter reveals that the presence of a region covering a cAMP-responsive element (CRE1 at -80) and a CAAT box is necessary for full response of the PEPCK promoter to glucocorticoids in well-differentiated rat hepatoma cells. In a cotransfection test, overexpression of the regulatory subunit of protein kinase A (PKA), causing sequestering of PKA, abolishes the glucocorticoid response of the promoter in well-differentiated cells. On the other hand, in dedifferentiated variants, overexpression of the catalytic subunit of PKA restores the response to glucocorticoids. The action of PKA on the glucocorticoid response requires the presence of the CRE1 element and is promoter specific because it does not concern nonhepatic promoters such as the long terminal repeats of the mouse mammary tumor virus. These results suggest that the full response of the PEPCK promoter to glucocorticoids requires activation of another signal transduction pathway, the cAMP-mediated pathway.
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PMID:Response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids depends on the integrity of the cAMP pathway. 781 33

Liver-selective transcription of the gene for rat arginase, an ornithine cycle (urea cycle) enzyme, is induced by glucocorticoids in a delayed secondary manner; the mRNA induction by the hormones requires de novo protein synthesis, and is preceded by a time lag of several hours. We searched for a DNA element mediating the glucocorticoid induction of the arginase gene with a transient transfection system using hepatoma cell lines. Within the 233-base pair region that is located 11 kilobases downstream from the transcription start site and that spans the junction of intron 7 and exon 8, we detected an enhancer element that is glucocorticoid-responsive and hepatoma cell-selective. The time course of the glucocorticoid induction through this enhancer element was delayed compared to that through the primary glucocorticoid-responsive mouse mammary tumor virus promoter. Footprint analysis revealed four protein-binding sites in this enhancer region. In gel retardation analysis, each site exhibited a complicated profile characterized by a number of shifted bands, some of which were tissue-selective and others ubiquitous. Gel shift competition and antibody supershift/inhibition analysis demonstrated that two of the four sites are recognized by members of the CCAAT/enhancer binding protein (C/EBP) family, some of which are liver-enriched.
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PMID:The delayed glucocorticoid-responsive and hepatoma cell-selective enhancer of the rat arginase gene is located around intron 7. 858 32

PSK, a protein-bound polysaccharide preparation obtained from cultured mycelia of the CM-101 strain of Coriolus versicolor belonging to basidiomycetes, is a biological response modifier capable of exhibiting diverse biological activities. This agent has been used clinically for the treatment of postoperative cancer patients in Japan by oral use. In this paper, chemopreventive aspects of PSK were reviewed. Oral administration of PSK reduced the incidence of tumor and/or prolonged the survival period in the following chemical carcinogen-induced, radiation-induced, and spontaneously developed animal cancer models: rat gastrointestinal cancer induced by 1,2-dimethylhydrazine; rat hepatoma by 3'-methyl-dimethylaminobenzene; mouse thymic lymphoma by whole-body irradiation; mouse spontaneous mammary tumor; and so on. PSK did not interact and/or inhibit drug-metabolizing enzymes and had no effect on the Ames test. On the other hand, this agent scavenged active oxygen through the induction of manganese superoxide dismutase, prevented the increase in frequency of anticancer agent-induced sister chromatid exchange, and suppressed fetal deformation induced by transplacental injection of teratogen, suggesting an effect on the initiation or promotion process of carcinogenesis. Also, PSK regulated cytokine production and enhanced the antitumor activity of effector cells such as killer T-cells and natural killer cells, suggesting an effect on the growth process after the development of malignant cells. Thus, this agent seems to act at multiple steps during carcinogenesis rather than a particular step. The main mechanism may be an antiteratogenic effect attributed to radical trapping, preventive effects against chromosome injury, and immunomodulative effects attributed to the modulation of cytokine production and effector cell function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:PSK as a chemopreventive agent. 831 80

Signal transduction by glucocorticoid hormones is mediated by the intracellular glucocorticoid receptor protein. The mechanisms determining cell type- or tissue-specific differences in hormone responsiveness remain, however, unclear. To address this issue we have used two different rat hepatoma cell lines, 762 and 6.10.2, respectively, in which mouse mammary tumor virus has been stably integrated. Nuclear extracts from both of these cell lines contained a factor that bound to a sequence motif extending from -163 to -147 in the mouse mammary tumor virus promoter and that appeared to repress hormonal induction of viral mRNA expression. Transient transfection experiments indicated that the cellular levels of this putative repressor did not affect basal promoter activity; this factor appeared rather to determine cellular sensitivity to glucocorticoids. Moreover, in these experiments the relative levels of the glucocorticoid receptor appeared to be the main determinant of maximum inducibility of virus expression by hormone. Taken together, these data indicate that the differential expression patterns of receptor versus the putative repressor protein may determine the level of hormonal responsiveness of target genes in glucocorticoid-sensitive tissues.
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PMID:The glucocorticoid receptor and a putative repressor protein coordinately modulate glucocorticoid responsiveness of the mouse mammary tumor virus promoter in the rat hepatoma cell line M1.19. 838 May 80


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