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)

CGP 6809 is a water-soluble nitrosourea derivative with quite distinct chemical and biological properties as compared with the well-known representatives of this class of compounds. It is related to the antibiotic streptozotocin, from which it is distinguished in the structure of the sugar moiety and the position of the methylnitrosourea residue. CGP 6809 possesses practically the same alkylating potential as streptozotocin; however, its carbamoylating activity is comparable with that of CCNU. In contrast to other nitrosourea derivatives, CGP 6809 showed relatively little activity in murine leukemias but was markedly active in solid transplantable melanomas (Harding-Passay, B16), in the 11095 prostate carcinoma, and in a substrain of Yoshida hepatoma (AH 7974) resistant to BCNU and CCNU. In the Ehrlich and Yoshida ascitic tumors complete responses were seen with no toxic death. Dose-dependent activity was found in the human lung carcinoma MBA 9812 and almost complete growth inhibition was achieved in the human melanoma WM 47 by both the oral and parenteral routes of administration. However, mammary tumor lines (Ca 755, 2661/61, R-3230AC), the Guerin-T8 uterus epithelioma, and the Rous sarcoma/S-R proved to be relatively refractory to this drug. This was also the case for the Lewis lung carcinoma implanted i.m. or s.c. However, development of lung metastases was markedly inhibited. Combination therapy using CGP 6809 with cyclophosphamide, 5-fluorouracil, or chlorambucil in the same model led to partial responses of the primary tumor as well as almost total eradication of lung metastases.
 ...
PMID:CGP 6809, a sugar-containing nitrosourea derivative: pharmacological and physicochemical properties. 271 56

We have used the chloramphenicol acetyltransferase (cat) gene expression system to study the effect of the X protein of hepatitis B virus (HBV) on viral enhancers. Plasmids containing the HBV enhancer and the core gene promoter linked to the cat gene were cotransfected with a plasmid containing the X gene into the human hepatoma cell line PLC/PRF/5. Our results indicate that the transfected X gene caused a trans-activation of the HBV enhancer. If a frameshift mutation or a deletion in the X structural gene was created, this trans-activation function was abolished. This result and the observation that the frameshift mutation did not alter the transcription of X mRNA suggest that the X protein is the trans-activating factor. Using similar techniques, we found that the X protein was also capable of trans-activating the simian virus 40 (SV40) and Rous sarcoma virus enhancers (pSV2cat and pRSVcat) in CV-1 cells. However, trans-activation of the SV40 enhancer by the X protein was not observed in COS-1 cells. By cotransfecting pSV2cat and the X gene with a plasmid containing either the intact SV40 genome, the SV40 genome devoid of the T-antigen (T-ag) gene, or only the T-ag gene, we demonstrated that SV40 T-ag can suppress trans-activation by the X protein. SV40 T-ag did not inhibit expression of the X gene or inactivate the X protein. The most probable mechanism of this inhibition is that T-ag competes with the X protein for a common target.
 ...
PMID:trans-activation of viral enhancers by the hepatitis B virus X protein. 282 5

Glyceraldehyde-3-phosphate dehydrogenase [GAPDH; D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12] mRNA levels are induced by physiologic concentrations of insulin in cultured 3T3-F442A adipocyte and H35 hepatoma cell lines. To examine the mechanism by which insulin regulates GAPDH mRNA levels in these two insulin-sensitive tissues, we have isolated a functional human GAPDH gene. When stably transfected and expressed in 3T3-F442A preadipocytes and H35 hepatoma cells, the intact human GAPDH gene is induced 10-fold by insulin in 3T3-F442A adipocytes and 3-fold by insulin in H35 hepatoma lines, which is similar to the induction obtained with the endogenous gene. A human GAPDH-chloramphenicol acetyltransferase construct, containing sequences -487 to +20 of the human gene fused to the chloramphenicol acetyltransferase gene, is regulated by insulin in stably transfected 3T3 adipocytes and stably or transiently transfected H35 hepatoma cell lines, whereas the Rous sarcoma virus-chloramphenicol acetyltransferase fusion protein is not. Thus, the inductive effect of insulin on human GAPDH gene expression is mediated through cis-acting sequences located between -487 and +20 of the human GAPDH gene.
 ...
PMID:Insulin stimulates glyceraldehyde-3-phosphate dehydrogenase gene expression through cis-acting DNA sequences. 283 30

Four glycosidases (beta-galactosidase, alpha-mannosidase, alpha-fucosidase and beta-N-acetylglucosaminidase) were studied in chicken normal and regenerating liver, in turkey poult liver and in virus induced avian tumors--chicken hepatoma (strain Mc-29), Rous sarcoma (strain Schmidt-Ruppin) and turkey poult hemocytoblastoma nodules (strain Mc-31). The multiple forms of beta-N-acetylglucosaminidase were assayed as well. A particular enzyme pattern was found in the tumor lines under investigation. A characteristic property of hepatoma cells was the elevation of beta-galactosidase activity and of the former enzyme and that of beta-N-acetylglucosaminidase for the hemocytoblastoma. In Rous sarcoma the glycosidase activities (except that of alpha-fucosidase) were much lower, compared to the other two solid tumors. All enzyme activities were compared with those in the normal liver of the corresponding avian species, and with the liver of tumor bearing fowls and with regenerating chicken liver. Unlike the rat liver in the avian normal and tumor tissues the percentual ratio between the multiple forms A and B of beta-N-acetylglucosaminidase was found to be 30:70%.
 ...
PMID:Glycosidases in normal and regenerating chicken liver, hepatoma Mc-29, Rous sarcoma, in turkey poult liver and hemocytoblastomes, provoked by the leukosis virus strain Mc-31. 298 24

The human P450IIE1 gene, coding for an ethanol-inducible nitrosamine-metabolizing P-450, was isolated from a lambda EMBL3 genomic library and completely sequenced. The human gene spanned 11,413 base pairs and contained nine exons and a typical TATA box. Upstream and downstream DNAs of 2788 and 559 base pairs were also sequenced and compared to the rat gene. Significant areas of sequence similarity were observed within 140 base pairs upstream of the transcription start site in the rat and human genes. Human DNA 539 base pairs upstream of the transcription start site was inserted into the expression vector pSVOAL delta 5', and luciferase activity was detected when the constructs were introduced into a rat hepatoma cell line. The activity was over 100-fold lower than that of pRSVL, a Rous sarcoma virus LTR-driven luciferase gene. By use of panels of rodent-human cell hybrids, the gene was mapped to chromosome 10 (CYP2E locus). A full-length cDNA, constructed with the first exon of the genomic clone and a partial cDNA clone, was expressed in COS cells and found to code for N-nitrosodimethylamine demethylase activity.
 ...
PMID:Human ethanol-inducible P450IIE1: complete gene sequence, promoter characterization, chromosome mapping, and cDNA-directed expression. 323 19

Most patients with hepatocellular carcinoma have an elevated alpha-feto-protein (AFP) level. This high level of AFP expression is transcriptionally controlled by the 5'-flanking sequence of the AFP gene. Using the 5'-flanking sequence as a promoter for the herpes simplex virus thymidine kinase (HSV-TK) gene in an adenoviral vector (Av1AFPTK1), the therapeutic efficacy of adenovirus-mediated HSV-TK gene transduction, followed by ganciclovir (GCV) administration, was studied in tumors in athymic nude mice. Av1AFPTK1 transduction of two cell lines demonstrated HSV-TK enzyme activity only in the AFP-producing cells (HuH7) and not in the AFP nonproducing cells (SK-Hep-1). As expected, only transduced HuH7 cells were killed by GCV treatment. Transduction by an adenoviral vector harboring a Rous sarcoma virus promoter and HSV-TK gene (Av1TK1) showed enzymatic activity and GCV killing in both cell lines. All HuH7 tumors that were transduced with either Av1AFPTK1 or Av1TK1 completely regressed after GCV treatment. On the other hand, there was complete regression of SK-Hep-1 tumors only when treated with Av1TK1 and GCV and not when treated with Av1AFPTK1 and GCV. Thus, cell-specific killing was achieved by adenoviral vector containing AFP promoter for the HSV-TK gene and GCV treatment.
 ...
PMID:Adenovirus-mediated gene therapy of hepatocellular carcinoma using cancer-specific gene expression. 758 89

An antiserum to the Rous sarcoma virus-transforming protein pp60v-src, raised in rabbits immunized with the bacterially produced protein alpha p60 serum (M. D. Resh and R. L. Erikson, J. Cell Biol. 100:409-417, 1985) previously reported to detect very specifically a novel population of pp60v-src and pp60c-src molecules associated with juxtareticular nuclear membranes in normal and Rous sarcoma virus-infected cells of avian and mammalian origin, was used here to investigate by immunofluorescence microscopy localization patterns of Src molecules in human cell lines, either normal or derived from spontaneous tumors. We found that the alpha p60 serum reveals nuclear and nucleolar concentrations of antigens in all the human cell lines tested and in two rat and mouse hepatoma cell lines derived from adult tumorous tissues but not in any established rat and mouse cell lines either untransformed or transformed by the src and ras oncogenes. Both the nuclear and nucleolar stainings can be totally extinguished by preincubation of the serum with highly purified chicken c-Src. We show also that the partitioning of the alpha p60-reactive proteins among the whole nucleus and the nucleolus depends mostly on two different parameters: the position in the cell cycle and the degree of cell confluency. Our observations raise the attractive possibility that, in differentiated cells, pp60c-src and related proteins might be involved not only in mediating the transduction of mitogenic signals at the plasma membrane level but also in controlling progression through the cell cycle and entry in mitosis by interacting with cell division cycle regulatory components at the nuclear level.
 ...
PMID:Highly specific antibody to Rous sarcoma virus src gene product recognizes nuclear and nucleolar antigens in human cells. 785 7

An avian hepatoma cell line has been reported to be suitable for the cultivation of avian laryngotracheitis virus (ILTV) (Scholz et al. (1993) J. Virol. Methods, 273-286; Guo et al. (1993) Am. J. Vet. Res., in press). To provide information for the establishment of avian expression systems and for the construction of avian recombinant viruses, five expression plasmids were constructed to test two avian viral and two mammalian viral promotors for their suitability and strength for gene expression in this cell line. Chicken hepatoma cells were transfected with plasmids carrying the bacterial beta-galactosidase (beta-gal) gene as a reporter gene. The beta-gal gene of three plasmid constructs expressed in both E. coli and avian hepatoma cells, while the beta-gal gene of two other constructs expressed only in avian hepatoma cells. The beta-gal gene expressed independently of any viral infection when under the control of the early Rous sarcoma virus (RSV) promoter or the immediate-early cytomegalovirus (CMV) promoter. However, expression of beta-gal gene under the control of the SV40 early promoter/enhancer and the ILTV TK promoter was greatly potentiated when the transfected cells were co-infected with ILTV. This finding provides a system for the enhancement of gene expression in avian cells, especially when ILTV is used as vector.
 ...
PMID:Transactivation of the early SV40 promoter by avian infectious laryngotracheitis virus in avian hepatoma cells. 810 2

Tumor and proliferating cells maintain a high glycolytic rate even under aerobic conditions. The discovery of fructose 2,6-bisphosphate, a potent stimulator of glycolysis, has prompted a re-investigation of this phenomenon. Rat hepatoma cells and fibroblasts stimulated by mitogens or transformed by the Rous sarcoma virus carrying the v-src oncogene were used as models. The results indicate that in established lines of hepatoma cells the biochemical properties of the bifunctional enzyme, PFK-2/FBPase-2, involved in the synthesis and degradation of fructose 2,6-bisphosphate, differ from those of the enzyme from normal liver. In addition, the stimulation of glycolysis induced by phorbol esters and pp60v-src can be explained by an increase in the concentration of fructose 2,6-bisphosphate and an activation of PFK-2. The mechanism of stimulation involves the transcription of a gene whose product activates PFK-2 or is a distinct PFK-2 isozyme. Finally, mercaptopurines were found to block fructose 2,6-bisphosphate synthesis in vitro and in lymphocytes and lymphoblastic cells. In these cells, this resulted in an inhibition of glycolysis.
 ...
PMID:Fructose 2,6-bisphosphate and the control of glycolysis by growth factors, tumor promoters and oncogenes. 839 37

The genomic region encoding the hepatitis C virus (HCV) core protein was cloned into a mammalian expression vector to study its role on the transcriptional regulation of cellular proto-oncogene and viral promoters. Using a transient transfection assay in human hepatocellular carcinoma (HepG2) cells, we demonstrate that the HCV core protein activates the human c-myc, Rous sarcoma virus long terminal repeat (LTR), and simian virus 40 (SV40) early promoters; and suppresses the c-fos promoter and human immunodeficiency virus type 1 (HIV-1) LTR activity. The transcriptional regulation of cellular proto-oncogenes by the HCV core protein suggests possible involvement of the core protein in the deregulation of normal hepatocyte growth and hepatocarcinogenesis.
 ...
PMID:Transcriptional regulation of cellular and viral promoters by the hepatitis C virus core protein. 853 58


<< Previous 1 2 3 Next >>