Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mutational analysis of the delta region of the Jun protein shows an inverse correlation between transforming and transactivation potential of the mutant proteins if both properties are measured in chicken embryo fibroblasts. The possibility that Jun acquires oncogenicity not by gain but by loss of function is also suggested by the down regulation of the differentiation control element MyoD by Jun and by the low transactivating potential of highly transforming chimeric proteins of Jun and JunD and Jun and herpes simplex VP16. These observations raise questions concerning the relative importance of positive and negative transcriptional control signals imitated by Jun.
Leukemia 1992
PMID:The oncogenicity of Jun. 160 20

The thymidine kinase gene (tk) of herpes simplex type 1 virus (HSV-1) was inserted into a retroviral vector under the transcriptional control of the enhancer-promoter element of the Moloney murine leukemia virus long terminal repeat. Replication-defective viral particles were obtained by transfection of vector DNA into the packaging cell line psi2 and were used to infect C6 rat glioma-derived cell lines in culture. The sensitivity of these cells to the toxic effects of the nucleoside analog ganciclovir was found to be significantly increased by transfer of the HSV-1 tk gene. The difference in sensitivity between infected and uninfected cells defined ganciclovir concentrations that could be used to selectively kill essentially all infected cells while sparing uninfected ones. C6 glioma cells introduced subcutaneously into nude mice were highly tumorigenic. Growth of tumors produced from C6-derived cells bearing the HSV-1 tk gene, but not parental C6 cells, could be inhibited by intraperitoneal administration of ganciclovir. This work demonstrates the effectiveness of the thymidine kinase expressed by the HSV-1 ks gene in sensitizing brain tumor cells to the toxic effects of nucleoside analogs. Retrovirus vectors should thus prove useful in the selective delivery of this killer gene to dividing tumor cells in the nervous system, where most endogenous cells are not dividing.
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PMID:Selective killing of glioma cells in culture and in vivo by retrovirus transfer of the herpes simplex virus thymidine kinase gene. 165 12

Action spectra of the antileukemic and antiviral activities of merocyanine 540 (MC540) were determined using L1210 leukemia cells and human Herpes simplex virus type 1. The major peak of both action spectra aligned closely with the absorption spectrum of membrane-bound dye monomer, and by implication, the action spectrum of 1O2 generation. These results are compatible with the notion that the antileukemic and antiviral activities of MC540 are primarily attributable to membrane-bound monomer and at least in part mediated by 1O2.
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PMID:Action spectra of the antileukemic and antiviral activities of merocyanine 540. 166 14

Hypericin is a polycyclic anthrone first isolated from the plant St. Johnswort and was shown to have dramatic anti-retroviral activity against Friend leukemia virus and radiation leukemia virus in mice. Hypericin displayed marginal activity (IC50 = 6 micrograms/ml) against Moloney murine leukemia virus (Mo-MuLV) in vitro. Hypericin did not display selective antiviral activity against herpes simplex virus, influenza A, adenovirus, or poliovirus. The 50% cytotoxic concentration was approximately 25 micrograms/ml. When virus was incubated with hypericin before infecting cells, the drug was virucidal to all enveloped viruses tested (herpes simplex, influenza virus A, and Mo-MuLV) at concentrations of 1.56 micrograms/ml to 25 micrograms/ml. Hypericin was not virucidal to the non-enveloped viruses tested (adenovirus and poliovirus). These data indicate that the mechanism of viral inactivation for hypericin is dependent upon the presence of a viral lipid envelope. In vivo, hypericin (50 mg/ml) was effective against FLV or HSV-1 if incubated with the virus for 1 h at 37 degrees C before infecting mice, but was not effective if pre-incubated with virus for 1 h at 4 degrees C or if administered concurrently with virus.
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PMID:Virucidal activity of hypericin against enveloped and non-enveloped DNA and RNA viruses. 169 94

The herpes simplex virus (HSV) immediate-early protein ICP27 has been postulated to play an auxillary role in HSV. gene expression, augmenting or inhibiting the activation of different viral promoters by the other immediate-early proteins ICPO and ICP4. Here we show that ICP27 alone can up-regulate gene expression of a retroviral vector containing Moloney murine leukemia virus (MoMuLV) regulatory sequences. This is the first report of an effect of ICP27 on gene expression driven by heterologous virus regulatory sequences. The effect does not involve the region of ICP27 which inhibits gene activation of HSV early gene promoters by ICPO and ICP4, but rather is dependent on the same region of ICP27 as is required to augment the activation of HSV late gene promoters by ICPO and ICP4. This indicates that the two activation effects are likely to operate via the same mechanism. Activation by ICP27 is dependent on the 3' LTR and adjacent region of MoMuLV but is independent of the promoter in the 5' LTR which can be replaced by a heterologous promoter such as that of SV40 without affecting activation by ICP27. The significance of this effect for an understanding of the mechanism of action of ICP27 and its role in regulating the gene expression of HSV and potentially of other viruses is discussed.
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PMID:Promoter-independent activation of heterologous virus gene expression by the herpes simplex virus immediate-early protein ICP27. 173 2

Tax1 of human T-cell leukemia virus type 1 (HTLV-1) activates viral transcription dependent upon three 21-bp enhancer elements in the long terminal repeat. Difficulties in detecting any association of Tax1 with the viral enhancer have hampered elucidation of the molecular mechanisms of Tax1-mediated transcriptional activation. By constructing a fusion protein with the heterologous DNA-binding domain of yeast GAL4, Tax1 was shown to be a potent transcriptional activator dependent on the presence of GAL4-binding sites. Deletions of the Tax1 portion of the fusion protein revealed that almost the entire region of Tax1 (amino acids 2-337) is required for activation, and the activity correlated well with that of the viral enhancer. The GAL/Tax1 mutant lacking 41 residues of the C-terminus of Tax1, GAL/Tax1(2-312), was inactive for the viral enhancer, but activity was recovered by adding the heterologous activation domain of herpes simplex virus VP16. These results indicate that Tax1 has two distinct but overlapping functional domains for transcriptional activation and for enhancer specificity. Thus, Tax1 is thought to be a transcription factor acting in the enhancer complex rather than as a catalytic or allosteric modifier of pre-existing cellular transcription factors.
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PMID:HTLV-1 Tax has distinct but overlapping domains for transcriptional activation and for enhancer specificity. 176 79

In an effort to clarify the effect of human T cell leukaemia virus type I (HTLV-I) infection on virus-specific CD8+ cytotoxic T cells, a herpes simplex virus-specific CD8+ cytotoxic T cell clone was infected with HTLV-I in vitro. The cytotoxic activity of the clone was found to have declined early after HTLV-I infection when the expression of T cell receptor-CD3 complex on the cell surface still showed no difference in comparison with that of uninfected parent cells. After 16 weeks of HTLV-I infection, expression of T cell receptor-CD3 complex on HTLV-I-infected clone cells became decreased. This phenomenon is similar to the effect of HTLV-I infection on CD4+ cytotoxic T cells as we previously reported, and suggests that there are common mechanisms of declined cytotoxic activity mediated by both CD4+ and CD8+ cytotoxic T cells following infection with HTLV-I. Such functional alterations of cytotoxic effector cells might be one of the mechanisms underlying immunodeficiency caused by HTLV-I infection.
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PMID:The effect of human T cell leukaemia virus type I infection on a herpes simplex virus-specific CD8+ cytotoxic T cell clone. 184 20

This paper reports on the role of endogenous and exogenous thiols in the merocyanine 540 (MC 540)-sensitized photoirradiation of L1210 leukemia cells, human erythrocytes, and human Herpes simplex virus type 1. Several measures taken to decrease the intracellular content of glutathione enhanced the cells' sensitivity to MC 540-sensitized photoirradiation while stimulation of glutathione biosynthesis or supplementation of the extracellular or extraviral thiol content decreased the photosensitivity of cells and viruses. Taken together, these data suggest that endogenous and exogenous thiols can modulate the sensitivity of cells and enveloped viruses to MC 540-sensitized photoirradiation. They also pose new questions as to the mechanism of MC 540-sensitized photolysis.
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PMID:Modulation by thiols of the merocyanine 540-sensitized photolysis of leukemia cells, red cells, and herpes simplex virus type 1. 185 5

Infection with human herpesvirus 6 (HHV-6) was found to up-regulate expression of human immunodeficiency virus and human T cell leukaemia virus type I (HTLV-I) long terminal repeat sequence (LTR), and herpes simplex virus type 1 (HSV-1) gD chloramphenicol acetyltransferase (CAT) constructs transfected into the T cell line, J. Jhan. Activation by HHV-6 was due to one or more viral proteins produced early in infection and, in the case of the HTLV-I LTR, was synergistic to induction mediated by the HTLV-I tax gene product. Neither the HTLV-I enhancer nor basal promoter elements of the HSV-1 gD gene were essential for activation and no increase in accumulated HTLV-I mRNA was observed due to HHV-6 infection. Induction by HHV-6 was found to be dependent on the reporter construct used, because the CAT gene and, to a lesser extent, the HSV-1 thymidine kinase gene were responsive to HHV-6 infection although no significant activation of growth hormone constructs was observed. Our results bear a strong resemblance to those obtained for the Epstein-Barr virus BMLF1 gene, indicating that the major HHV-6 trans-activator may be a homologue of this gene.
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PMID:Activation of gene expression by human herpesvirus 6 is reporter gene-dependent. 185 12

Toward gene therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in AIDS, Moloney murine leukemia virus-derived retroviral vectors were engineered to allow constitutive and tat-inducible expression of an HIV-1 5' leader sequence-specific ribozyme (Rz1). These vectors were used to infect the human CD4+ lymphocyte-derived MT4 cell line. The stable MT4 transformants expressing an HIV-1 RNA-specific ribozyme, under the control of the herpes simplex virus thymidine kinase (tk) promoter, were found to be somewhat resistant to HIV-1 infection as virus production was delayed. In cells allowing ribozyme expression under control of the simian virus 40 or cytomegalovirus promoter, the rate of HIV-1 multiplication was slightly decreased, and virus production was delayed by about 14 days. The highest level of resistance to HIV-1 infection was observed in MT4 cells transformed with a vector containing a fusion tk-TAR (trans activation-responsive) promoter to allow ribozyme expression in a constitutive and tat-inducible manner; no HIV-1 production was observed 22 days after infection of these cells. These results indicate that retroviral vectors expressing HIV-1 RNA-specific ribozymes can be used to confer resistance to HIV-1 infection.
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PMID:Resistance to human immunodeficiency virus type 1 (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme. 189 2


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