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)

Hepatocyte growth factor (HGF) is a potent mitogen for primary hepatocytes. Therefore, we examined HGF as a possible autocrine growth factor in hepatocellular carcinoma (HCC). We introduced an albumin-HGF expression vector into Fao HCC cells and transgenic mice. Expression of the albumin-HGF vector in Fao HCC cells inhibited their growth in vitro. In vivo, FaoHGF cells produced tumors that averaged 10% of the sizes of G418-resistant controls when transplanted into nude mice. In contrast, hepatocytes from transgenic mice expressing HGF grew more rapidly than did those from normal siblings. Further, growth of eight additional HCC cell lines was inhibited by the addition of recombinant HGF. Finally, of 35 tumor cell lines surveyed, only 6 cell lines expressed HGF mRNA, and no HCC cell line expressed HGF. Although HGF stimulates normal hepatocytes, it is a negative growth regulator for HCC cells.
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PMID:Hepatocyte growth factor inhibits growth of hepatocellular carcinoma cells. 130 12

Angiotensinogen mRNA is found in many extrahepatic tissues, where it may participate in local angiotensin-generating systems. In this study we explore the feasibility of using anti-sense RNA to decrease angiotensinogen production in rat H4IIEC3 hepatoma cells. An amplifiable shuttle vector was modified to allow the production of high levels of stable anti-sense RNA from two regions of the mouse angiotensinogen gene under the control of the inducible sheep metallothionein promoter. Stably transformed, clonal cell lines expressing anti-sense RNA for angiotensinogen were isolated after selection with the aminoglycoside G418. Subsequently, the number of chromosomally integrated copies of the angiotensinogen anti-sense constructs was coamplified by methotrexate selection for dihydrofolate reductase activity carried on the shuttle vector. With a 20- to 30-fold induction of the anti-sense RNAs, the target angiotensinogen mRNA level was reduced to 25-30% of control values. The specificity of this effect was confirmed by showing no decrease in either beta-tubulin or neomycin phosphotransferase mRNA levels. Using tissue-specific promoters, it should be possible to direct these effects to specific organs in transgenic mice. However, in agreement with results from other groups, our findings suggest that it will not be possible to eradicate completely the target gene product using the anti-sense RNA strategy.
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PMID:Inducible anti-sense RNA for angiotensinogen in stably transformed hepatoma cell lines. 169 79

Complement-mediated cytolysis of the mouse mammary tumor virus (MMTV)-infected rat hepatoma (HTC) cell line, M1.54, resulted in recovery of a mutant derivative, designated CR5, in which the magnitude of both basal and dexamethasone-induced proviral MMTV RNA expression was selectively reduced. Variant CR5 cells were transfected with a plasmid containing the glucocorticoid-regulated MMTV promoter linked to the neomycin resistance gene (pLNL). Half-maximal resistance to G418 killing was glucocorticoid inducible in both pLNL-transfected CR5 and M1.54 cells and was dependent on glucocorticoid receptor occupancy. The down-transcription of MMTV provirus sequences cannot be conferred to transfected genes driven by the same viral promoter suggesting that CR5 cells are defective in cis acting factors. Consistent with this notion, indirect immunofluorescence of transient heterokaryons revealed that uninfected wild-type HTC cells failed to complement the defect in CR5 while CR5 cells did not suppress the wild-type phenotype of M1.54 cells.
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PMID:Glucocorticoid responsiveness of mouse mammary tumor virus (MMTV) promoters in a down-transcription hepatoma tissue culture (HTC) variant. 254 81

Upstream sequences of the human P450IA1 gene were inserted into a promoterless expression vector (pSVO-cat) containing the chloramphenicol acetyltransferase (CAT) gene, with and without the Harvey murine sarcoma virus (Ha-MSV) core enhancer, and either plasmid was transfected into human breast carcinoma MCF-7 and MDA-231 and mouse hepatoma Hepa-1 cell lines. In most instances constitutive and inducible CAT activities in the transient CAT expression assay were similar (within 3-fold) to those in the stable transformation CAT assay (selection of G418-resistant colonies following co-transfection with pSV2-neo). In the case of Ha-MSV-containing constructs stably integrated in the two human breast cancer lines, however, CAT expression was more than two orders of magnitude greater than that transiently expressed in these cells. Since the major difference between these two assays is plasmid copy number, these data suggest the presence of limiting amounts of tissue-specific positive-control enhancer-binding factor(s) in the breast carcinoma cell lines.
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PMID:Human P45IA1 upstream regulatory sequences expressing the chloramphenicol acetyltransferase gene. Effect of Ha-MSV enhancer and comparison of transient with stable transformation assays. 282 73

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to interact with a cytosolic receptor and, in turn, activate transcription of the mouse P1(450) gene. Various lengths of DNA upstream of the P1(450) gene were inserted into the pSV0-cat expression vector, with and without addition of the Harvey murine sarcoma virus (Ha-MSV) 72-bp repeat enhancer element. The constructs were cotransfected with pSV2-neo into mouse hepatoma wild-type cells and two variant cell lines. One variant is believed to result from a mutation in the P1(450) structural gene and expresses high levels of P1(450) mRNA constitutively; the other variant has a defect in nuclear translocation of the inducer-receptor complex. After selection in G418, the cells were treated with control medium, TCDD, cycloheximide, or TCDD plus cycloheximide and then assayed for chloramphenicol acetyltransferase (CAT) activity. The data are consistent with the presence of several functional regions within the upstream sequence: a promoter region, a region that is negatively autoregulated, possible repressor-binding and inducer-receptor complex-binding sites, and an upstream activation element that is required for transcriptional activation by TCDD. The Ha-MSV enhancer can substitute for this upstream activation element.
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PMID:Autoregulation plus upstream positive and negative control regions associated with transcriptional activation of the mouse P1(450) gene. 299 46

The presence of activated transforming genes was investigated in four primary aflatoxin-induced rat liver tumors in male Fischer rats, in two cell lines generated from such tumors, in an epithelial liver-derived nontransformed cell line, and in the latter cell line after transformation by aflatoxin B1 in vitro. When DNA extracted from these sources was transfected into NIH 3T3 cells, negative results were obtained from focus assays. Cotransfection of these DNA samples with a gene for resistance to G418, followed by selection for resistance to that antibiotic, and tumorigenicity testing in nude mice demonstrated DNA-mediated transfer of the neoplastic phenotype in all cases except for DNA from the nontransformed cell line. DNA extracted from these primary nude mouse tumors used in a secondary round of transfection with NIH 3T3 cells gave positive results in focus assays, which were conserved through succeeding rounds of transfection. By use of appropriate radiolabeled probes, activated ras oncogenes were detected in all samples. N-ras activation was detected in three of the primary rat liver tumors and both hepatoma cell lines. Ki-ras activation was detected in one primary rat liver tumor, and Ha-ras activation was detected in the cell line transformed in vitro with activated aflatoxin B1. The activated Ki-ras oncogene was further characterized by use of synthetic oligonucleotide probes and was shown to contain a G----A transition at the second nucleotide in codon 12.
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PMID:Activation of ras oncogene in aflatoxin-induced rat liver carcinogenesis. 328 72

Human x mouse microcell hybrids resistant to G418 were constructed between mouse hepatoma cells and human x mouse whole cell hybrids containing only intact human chromosome 5 and 22 with an integrated neor-gene. Among these, microcell hybrid BG15 produced four subclones, BG15-4, BG15-6, BG15-7 and BG15-9, which contained variously sized complements of human chromosome 5. BG15-6 contained an intact human chromosome 5, BG15-7 a deleted human chromosome 5 (5pter-q22) and BG15-4 and BG15-9 a translocation between parts of human chromosome 5 (pter-qter? and pter-q23, respectively) and a mouse chromosome. Southern DNA blot analysis showed that the human dihydrofolate reductase (DHFR) gene was present in all four subclones, whereas the human homolog of the v-fms gene was present in BG15-4 and 15-6, but absent from BG15-7 and 15-9. BG15-4, 15-6 and 15-9 were sensitive to diphtheria toxin, and only BG15-7 was resistant to the toxin. We used these microcell hybrids to restrict further the regional location of the gene for diphtheria toxin sensitivity to the q23 region of human chromosome 5.
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PMID:Regional assignment of the gene for diphtheria toxin sensitivity using subchromosomal fragments in microcell hybrids. 343 21

The therapeutic effect of the fibroblast-mediated human interferon (IFN alpha) gene therapy in combination with interleukin-2 (IL-2) activated killer cells (AK)/doxorubicin (i.e., adoptive chemoimmunotherapy) on nude mice bearing the human hepatocellular carcinoma (HCC) was investigated. A fibroblast cell clone (NIH3T3-IFN alpha+) secreting 1024 U/ml human IFN alpha was obtained from 14 positive clones by BMGNeo-IFN alpha DNA transfection, G418-resistant selection, limiting dilution and assay of IFN alpha activity. After i.p. implantation of NIH3T3-IFN alpha+ encapsulated into collagen, serum human IFN alpha activity could be detected from 12 h to day 15 with a peak at 72 h. AK were prepared from human peripheral mononuclear cells costimulated in vitro by IL-2 and inactivated human SMMC 7721 HCC cells. When the NIH3T3-IFN alpha+ cells were i.p. implanted into the HCC-bearing nude mice, the grown of HCC was inhibited and the survival time of the mice was extended. The growth of HCC was inhibited more obviously when AK was i.v. injected and IL-2 was i.p. injected after the NIH3T3-IFN alpha+ cells had been implanted. The best therapeutic effect was achieved when NIH3T3-IFN alpha+ cells were used in combination with IL-2/AK/doxorubicin. All these results suggested that the fibroblast-mediated human IFN alpha gene therapy could be used to treat the human hepatocellular carcinoma effectively and that when used in combination with IL-2-based adoptive chemoimmunotherapy, the therapeutic effect would be better.
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PMID:Treatment of human hepatocellular carcinoma by fibroblast-mediated human interferon alpha gene therapy in combination with adoptive chemoimmunotherapy. 764 87

A recombinant retroviral vector was constructed which expressed antisense RNA of c-ets-2, c-myc and N-ras. The pseudotype virus was packaged and rescued by transfection in PA317 cells and used to infect human hepatoma cell line SMMC-7721. After selection with G418, resistant colonies were obtained. Stable integration of retrovirus in infectants was shown by Southern hybridization of genomic DNA and the presence of antisense RNA was detected by RNA dot blot hybridization. It was demonstrated that the antisense RNAs did inhibit the growth of human SMMC-7721 hepatoma cells. The ability to form colony in soft agar and tumorigenicity in nude mice of SMMC-7721 were significantly suppressed by the antisense RNAs. The result implicates the potential value in future cancer gene therapy.
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PMID:[Reversal of malignant phenotype of human hepatoma cells by antisense c-ets-2, c-myc and N-ras]. 780 49

Truncated transcripts terminating within the HBx frame have been recognized previously in tumor and liver tissue of HCC patients. In this study biological activities of a predicted truncated HBx fused to a polylysin stretch (HBtx-polylysin) and of full length HBx were compared in NIH3T3 cells transfected with respective cDNA plasmids. Transactivation of a co-transfecting reporter gene and influence on neor DNA mediated transformation to G418 resistance were determined. In comparison to full length HBx the data indicate for HBtx-polylysin a lower transactivating capacity and as judged by the yield of colonies on a solid surface, a lower capacity to stimulate neor DNA mediated transformation. In soft agar the outgrowth into G418 resistant colonies was dependent on co-transfecting HBx cDNA. In providing this condition HBtx-polylysin had a much higher relative activity than full length HBx. Large cointegrants consisting of the plasmids carrying truncated HBx cDNA and neor DNA respectively were identified by chromosomal in situ hybridization. Based on Southern blot analyses extended concatemeres of the HBx cDNA plasmid constituted a main part of the cointegrants. Expression of truncated HBx cDNA was followed on the RNA and the protein level. The presence of this cDNA could be correlated to a compact spindle like cell appearance, its loss after prolonged passaging in the absence of G418 to a concomitant reversion to the phenotype of the NIH3T3 cell. Interspersed selection for G418 resistance stabilized the morphologically transformed phenotype. These results provide a basis to manipulate expression of truncated HBx and to recognize thereby processes leading to transformation.
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PMID:Biological activities of a putative truncated hepatitis B virus X gene product fused to a polylysin stretch. 805 25


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