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)

The suitability for field use of heating up to 80 degrees C and adding six different virucidal chemicals for decontamination of drinking and surface water was investigated using the viruses of Polio (vaccine strain), ECBO, Reo, bovine Parvo, HCC, Pseudorabies, ND and Vaccinia. The Parvovirus (concentration 10(5) TCID50/ml) heated to 80 degrees C could not be inactivated completely in drinking water within one hour; the Reovirus could after one hour only at 60 degrees C. The other viruses used lost their infectivity at 56 degrees C within 60 minutes or at 60 degrees C within 20 minutes respectively. Heating therefore seems to be too circumstantial a method for viral decontamination of water and unreliable under field conditions. As to the chemical water additives tested, chloramine-T, hydrogen peroxide and sodium peroxide proved to be unsuitable in spite of virucidal activity. The amount of their concentration necessary for reliable virus inactivation makes the water unfit for drinking. Iodine, a calcium hypochlorite sample and potassium permanganate were useful. Because of its constant reaction in drinking water together with additional advantages, iodination of water would seem to be the best method at present for viral water decontamination usable under field conditions.
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PMID:[Studies on inactivation of viruses in drinking and surface water. A contribution to the decontamination of water by field methods (author's transl)]. 61 Feb 55

The present study establishes the in vitro system for studying the oncosuppression activity of parvovirus and discovers that parvovirus H-1 can be grown cytolytically in various human cancer cell lines, which include 4 hepatoma cell lines (QGY-7703, SMMC-7721, Bel-7402, PLC/PRF/5), 3 gastric cancer cell lines (SGC-7901, MGC-80-3, MKN-28) and 1 naspharynx cancer cell line (CNE). The growth of two primary gastric cancer cell cultures from surgical cancer tissue were also inhibited by the infection of H-1. The sensitivity of cancer cells to H-1 may relate to their differentiation states. On the contrary, H-1 can neither be grown cytolytically in normal liver or stomach cells, nor inhibit their growth. Transformation of human skin fibroblasts with Simian Virus 40 activated their sensitivity to H-1. Our results thus indicate that the antineoplastic activity of H-1 in vivo involves at least its direct inhibiting or killing malignant cells.
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PMID:Inhibitory effect of parvovirus H-1 on cultured human tumour cells or transformed cells. 283 2

Several classes of viruses are in use, or are being developed, as gene therapy vectors. Viruses with small genomes containing few essential genes have the advantage of requiring only simple complementation systems to allow packaging of foreign DNA, substituted for the entire viral coding sequences. Retroviruses and the dependent parvovirus AAV (adeno-associated virus) have been used in this way, and both possess an efficient integration mechanism which should allow long-term expression of transduced genes. In some situations, however, long-term persistence may be undesirable and there is a need for small, non-integrating viral vectors. Autonomous parvoviruses, such as LuIII, have potential as such vectors for short-term expression of therapeutic genes. We previously described recombinants of LuIII that transduced reporter genes, expressed using the viral constitutive promoter, P4. We have now generated several recombinants containing regulated promoters. A virus including a liver-specific enhancer directed 10- to 20-fold preferential expression of the luciferase reporter in transduced human hepatoma (HepG2) versus HeLa cells. In additional LuIII recombinants, the luciferase reporter was linked with chimeric promoters containing binding sequences for either the yeast GAL4 protein or the bacterial tetracycline repressor. Luciferase expression was strongly activated when these viruses were used to infect cells containing a cognate trans-activator (GAL4 or tTA, a tetracycline repressor fusion with VP16 of herpes simplex), introduced by transfection. The response to tTA could be abolished, or reduced in a graded manner, by exposure of the infected cells to tetracycline. Further results suggested that an increase in basal expression, apparently mediated by the viral left terminal inverted repeat, could be minimized by interposing polyadenylation signals between this sequence and the promoter. These results confirm that appropriate transcriptional regulation can be achieved for genes transduced by an autonomous parvovirus vector. Such vectors therefore show promise for the delivery of therapeutic genes in situations requiring cell-specific, short-term expression, eg in targeting suicide genes for ablation of cancer cells.
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PMID:Autonomous parvovirus transduction of a gene under control of tissue-specific or inducible promoters. 892 9

A small percentage of persons with hepatocellular carcinoma (HCC) lack identifiable causes of liver pathology. The single-stranded DNA virus, TT virus (TTV), has been found in persons with acute and chronic liver injury. Nested polymerase chain reaction was used to search for both TTV and parvoviruses in 293 HCC samples from Asia and Europe. TTV was found in >30% of Chinese and Italian samples but in only 13% of French samples. No clinicopathologic differences were found between TTV-positive and -negative populations. A significant association was found between TTV infection and hepatitis B virus (P<.01) and herpesviruses (P<.02) in HCC patients, suggesting that factors promoting these infections are associated with enhanced TTV positivity. Parvovirus B19 and adeno-associated virus were found in only 7.5% of the tumors. Taken together, these data suggest that TTV infection is unlikely to be associated with the induction or acceleration of the hepatocarcinogenic process in humans.
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PMID:Effect of TT virus infection on hepatocellular carcinoma development: results of a Euro-Asian survey. 1072 May 42

A transplantable human hepatoma model, the QGY-9204, was used in this study. The growth kinetics of hepatoma in nude mice were compared after injection of parvovirus H-1 into the tumor growth. Significant difference in growth curves were seen between injected groups with H-1 dosages of 5 x 10(7) PFU and 5 x 10(8) PFU and that of control. It indicated that parvovirus H-1 was capable of suppressing the growth of human hepatoma. Previous studies showed H-1 is oncotropic, oncosuppressive and oncolytic. For histological, ultrastructural and histochemical examinations, transplantable hepatomas were taken at different time interval post H-1 (1 x 10(8) PFU per tumor growth) injection. For H-1 DNA amplification and H-1 nonstructural protein expression, PCR and ABC approach in hepatoma paraffin sections were used. The H-1 treated groups exhibited obvious signs of necrosis. It started on 3rd day post infection (3 d.p.i.) and the area of necrosis enlarged consecutively on 7 d.p.i., 10 d.p.i. and 14 d.p.i., but none was seen in saline-injected group even on 14 d.p.i. H-1 virions were also detected in the damaged tumor cells with numerous vacuoles in cytoplasm. Specific band (908 bp) of H-1 DNA and ABC immunostaining indicated H-1 DNA replication and NS-1 expression in tumors of treated groups, their time course was well in accordance with that process of necrosis. These results suggest that parvovirus H-1 promotes tumor necrosis by its DNA replication and cytotoxic NS-1 protein expression, and thus, it inhibits hepatoma growth and induces oncosuppression and oncolysis.
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PMID:[Inhibition of parvovirus H-1 on transplantable human hepatoma and its histological and histobiochemical studies]. 1103 20

Autonomous parvoviruses preferentially replicate in and kill in vitro-transformed cells and reduce the incidence of spontaneous and implanted tumors in animals. Because of these natural oncotropic and oncolytic properties, parvoviruses deserve to be considered as potential antitumor vectors. Here, we assessed whether parvovirus H1 is able to kill human hepatoma cells by induction of apoptosis but spares primary human liver cells, and whether the former cells can efficiently be transduced by H1 virus-based vectors. Cell death, infectivity, and transgene transduction were investigated in Hep3B, HepG2, and Huh7 cells and in primary human hepatocytes with natural and recombinant H1 virus. All hepatoma cells were susceptible to H1 virus-induced cytolyis. Cell death correlated with H1 virus DNA replication, nonstructural protein expression, and with morphological features of apoptosis. H1 virus-induced apoptosis was more pronounced in p53-deleted Hep3B and p53-mutated Huh7 cells than in HepG2 cells which express wild-type p53. In Hep3B cells, apoptosis was partially inhibited by DEVD-CHO, a caspase-3 inhibitor. In contrast, H1 virus-infected primary hepatocytes were neither positive for nonstructural protein expression nor susceptible to H1 virus-induced killing. Infection with a recombinant parvovirus vector carrying the luciferase gene under control of parvovirus promoter P38 led to higher transgene activities in hepatoma cells than in the hepatocytes. Taken together, H1 virus kills human hepatoma cells at low virus multiplicity but not primary hepatocytes. Thus, recombinant H1 viruses carrying antitumor transgenes may be considered as potential therapeutic options for the treatment of hepatocellular carcinomas.
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PMID:Effective infection, apoptotic cell killing and gene transfer of human hepatoma cells but not primary hepatocytes by parvovirus H1 and derived vectors. 1133 86

DNA structure and expression of p53 gene in human hepatoma cell lines SMMC-7721, YY-8103 and a spontaneously transformed liver cell line L-02 were analysed using the following method: analysis of allelic losses on chromosome 17p, PCR/SSCP, Northern blot and immunoprecipitation. There was no point mutation found in the exons 4-9 of the p53 gene, and a low level of expression of p53 gene was detected in the three cell lines. These observations were in agreement to the reported results of the relevant experiment using the human hepatoma cell line QGY-7703. Sensitivities of these cell lines and other eight human hepatoma cell lines (QGY-7703, PLC/PRF/5, Tong/HCC, Huh-7, FOCUS, Hep3B, SK-Hep-1, HepG2) with known p53 backgrounds to parvovirus H-1 was assayed using MTT method. Abnormality in the structure and/or function was observed in all of the cell lines examined except HepG2. The cell line HepG2 with normal structure and function of the p53 gene was found to be the least sensitive to H-1 in comparison to all the cell lines which have defeated structure and/or function of the p53 gene. The present study serves as a preliminary evidence that enhancement of the sensitivity of human hepatoma cell lines to H-1 is correlated to the abnormality of the structure and/or function of the p53 gene.
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PMID:[p53 gene expression of human hepatoma cell lines and their sensitivities to parvovirus H-1]. 1254 91

Over the last few years, naturally occurring or genetically manipulated oncolytic viruses gained increasing attention as novel therapeutics for cancer treatment. The present work provides proof of principle that an organotropic cell-based carrier system is suitable to deliver oncolytic parvoviruses to a tissue known to be a target for the formation of metastases. Carrier cells were inactivated by gamma-irradiation after infection, which was found not to affect the production and release of parvoviruses that were capable of lysing cocultured target neoplastic cells. Although systemically administered parvovirus H-1 showed a pronounced therapeutic effect against the development of established Morris hepatoma (MH3924A) lung metastases, the carrier cell strategy offered a number of advantages. Infected carriers were able to sustain H-1 virus expression for 6 days in the lungs of rats affected by metastatic disease and to reduce the spreading of the virus to peripheral organs. Compared to direct virus injection, the carrier cell protocol led to an improved therapeutic effect (metastases suppression) and a lesser generation of virus-neutralizing antibodies. These data support the use of carrier cells to deliver oncolytic viruses and/or viral vectors locally in tumors and, more particularly, metastases.
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PMID:Carrier cell-mediated delivery of oncolytic parvoviruses for targeting metastases. 1499 84

Parvovirus B19 (B19 virus) can persist in multiple tissues and has been implicated in a variety of diseases, including acute fulminant liver failure. The mechanism by which B19 virus induces liver failure remains unknown. Hepatocytes are nonpermissive for B19 virus replication. We previously reported that acute fulminant liver failure associated with B19 virus infection was characterized by hepatocellular dropout. We inoculated both primary hepatocytes and the hepatocellular carcinoma cell line Hep G2 with B19 virus and assayed for apoptosis by using annexin V staining. Reverse transcriptase PCR analysis and immunofluorescence demonstrated that B19 virus was able to infect the cells and produce its nonstructural protein but little or no structural capsid protein. Infection with B19 virus induced means of 28% of Hep G2 cells and 10% of primary hepatocytes to undergo apoptosis, which were four- and threefold increases, respectively, over background levels. Analysis of caspase involvement showed that B19 virus-inoculated cultures had a significant increase in the number of cells with active caspase 3. Inhibition studies demonstrated that caspases 3 and 9, but not caspase 8, are required for B19 virus-induced apoptosis.
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PMID:Parvovirus B19-induced apoptosis of hepatocytes. 1522 Apr 51

Autonomous parvoviruses are characterized by their stringent dependency on host cell S phase and their cytopathic effects on neoplastic cells. To better understand the interactions between the virus and its host cell, we used oligonucleotide arrays that carry more than 19,000 unique human gene sequences to profile the gene expression of the human hepatocellular carcinoma cell line QGY-7703 at two time points after parvovirus H-1 infection. At the 6-h time point, a single gene was differentially expressed with a >2.5-fold change. At 12 h, 105 distinct genes were differentially expressed in virus-infected cells compared to mock-treated cells, with 93% of these genes being down-regulated. These repressed genes clustered mainly into classes involved in transcriptional regulation, signal transduction, immune and stress response, and apoptosis, as exemplified by genes encoding the transcription factors Myc, Jun, Fos, Ids, and CEBPs. Quantitative real-time reverse transcription-PCR analysis on selected genes validated the array data and allowed the changes in cellular gene expression to be correlated with the accumulation of viral transcripts and NS1 protein. Western blot analysis of several cellular proteins supported the array results and substantiated the evidence given by these and other data to suggest that the H-1 virus kills QGY-7703 cells by a nonapoptotic process. The promoter regions of most of the differentially expressed genes analyzed fail to harbor any motif for sequence-specific binding of NS1, suggesting that direct binding of NS1 to cellular promoters may not participate in the modulation of cellular gene expression in H-1 virus-infected cells.
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PMID:Expression profiling of human hepatoma cells reveals global repression of genes involved in cell proliferation, growth, and apoptosis upon infection with parvovirus H-1. 1568 29


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