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)

Proliferative and interleukin responses to T-cell mitogens such as concanavalin A (Con A) were rapidly and progressively reduced in BALB/c mice infected with the Friend leukemia complex (FLC) or its helper, Friend murine leukemia virus (F-MuLV). In contrast, a combination of the protein kinase C activator phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) and the Ca++ ionophore A23187 elicited a normal lymphoproliferative response up to 8 days postinfection (p.i.) and normal interleukin-2 (IL-2) and interferon-gamma responses up to day 14 p.i. Exogenous IL-2 failed to restore the lymphoproliferative response of infected cells regardless of the stimulation used. These results showed that the T-cell deficits may be at least partly attributable to a derangement of the signal transduction pathway leading to activation. Spleen cells passed through nylon wool columns reacquired a normal responsiveness to Con A +/- TPA up to 14 days p.i. The latter finding suggests that the alterations in signal transduction are not caused by primary defect of the responder-T cells but may result from an extrinsic suppressive mechanism.
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PMID:Alterations of T-cell functions during Friend leukemia complex infection: defective signal transduction? 181 Mar 22

Inhibitors of glycoprotein processing enzymes have been shown to have activity against HIV. Several analogues of the known glucosidase I inhibitor, castanospermine (CAST), were synthesized and evaluated for their inhibitory effect on glucosidases and for antiviral activity against Moloney murine leukemia virus (MOLV) and HIV-1. The most effective analogue was 6-O-butanoyl CAST (B-CAST, MDL 28,574) with an IC50 of 0.05 micrograms/mL against MOLV. A correlation between inhibition of glucosidase I and MOLV replication was observed. This analogue was further evaluated against HIV-induced syncytial formation in HeLa T4+ cells and against productive infection in JM cells infected with HIV 1 (GB8 strain). B-CAST showed an IC50 of 0.3 micrograms/mL in the HeLa T4+ assay, compared to CAST at 11 micrograms/mL. The compound also was more potent (IC50:0.15 micrograms/mL) than CAST (4-6 micrograms/mL) in JM cells. The antiretroviral activity of B-CAST was further confirmed in Friend leukemia virus (FLV) infection in mice. B-CAST showed equivalent activity to AZT and was more potent than CAST in inhibiting FLV-induced splenomegaly in mice. The data presented herein suggest the potential of these novel glucosidase inhibitors as anti-HIV agents.
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PMID:Inhibition of glycoprotein processing and HIV replication by castanospermine analogues. 207 38

Analysis of expression of the Friend murine leukemia virus (F-MuLV) and of the spleen focus forming virus (SFFV) has been undertaken in highly malignant interferon (IFN)-sensitive (745) and IFN-resistant (3Cl-8) Friend leukemia cells (FLC), serially passaged intraperitoneally in DBA/2 mice. In vivo passaged 745 cells, as well as the clones derived thereof, did not release Friend virus (FV). Western blot analysis of the plasma membrane fractions of the virus nonproducer 745 cells revealed the lack of gp69/70 glycoprotein expression. At least 10 intraperitoneal passages of virus producer in vitro passaged of virus producer in vitro passaged 745 cells were necessary to obtain the selection of the virus nonproducer phenotype. In contrast in vivo passaged 3Cl-8 cells continued to produce FV even after 100 in vivo passages and expressed gp69/70 antigens to a similar extent as the original in vitro passaged FLC. The expression of F-MuLV and SFFV RNAs in virus producer and virus nonproducer FLC clones has been investigated by means of Northern blot technique using probes specific for either F-MuLV or SFFV. No F-MuLV specific RNA sequences were detected in virus nonproducer 745 clones. SFFV specific RNA transcripts and gp52/55 glycoprotein production could be revealed in all the FLC tested. Southern blot analysis showed the presence of F-MuLV specific sequences in the cellular DNA of virus nonproducer 745 clones. As both in vivo passaged F-MuLV producer 3Cl-8 and F-MuLV nonproducer 745 cells were equally barely immunogenic and highly malignant when injected into syngeneic DBA/2 mice, these results indicate that F-MuLV expression does not result per se in a high immunogenic potential of tumor cells. For the time being, as a specific property of 3Cl-8 versus 745 cells is the interferon-resistant phenotype, it is tempting to speculate that the selection of virus nonproducer cell variants after in vivo passages of interferon-sensitive 745 cells could depend on the presence of low levels of endogenous interferon in normal young mice.
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PMID:Friend murine leukemia virus and spleen focus-forming virus expression in highly malignant interferon-sensitive and interferon-resistant Friend leukemia cells. 242 80

We have previously shown that mice simultaneously infected with the murine mammary tumor virus (MuMTV) and with certain slow murine leukemia viruses (MLV) have an increased resistance to the pathological effects of both agents. Here we report that milk-transmitted MuMTV also delays the development of the acute erythroleukemia induced by Friend leukemia virus (FLV), and retards, or prevents in some cases, the development of long-term lymphomas caused by its helper component. This is confirmed by the observation that the average life span of MuMTV-carrying mice infected with FLV or its helper component is prolonged by over 30% as compared to that of MuMTV-free animals infected with the same agents and by the finding that the replication of Friend viruses is reduced in mice neonatally exposed to MuMTV. Since the antibody responses of mice to MuMTV and to FLV were not cross-reactive, we searched for antiviral activity in the tissues of mice exposed to MuMTV, FLV, or the helper component of FLV. Low levels of interferon-alpha/beta were consistently detected in spleen extracts from mice infected with all these agents but could not be demonstrated in the spleens of uninfected BALB/c mice; thus, the chronic production of endogenous interferon is likely to play a major role in the reciprocal interference in vivo between retroviruses belonging to different genera.
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PMID:Reciprocal interference between milk-transmitted mammary tumor virus and Friend leukemia viruses in mice: possible role of the interferon system. 242 40

Anti-lymphoma natural resistance (NR) has been detected in DBA/2 mice inoculated intravenously (iv) with syngeneic Friend leukemia cells (FLC). Interferon-sensitive 745 or interferon-resistant 3Cl-8 clones, passaged in vitro and exhibiting "low" tumorigenicity in syngeneic DBA/2 mice, were used. NR, measured as rapid clearance of radiolabeled cells from lung and liver of recipient mice, was age-dependent, was boosted by host pretreatment with polyinosinic-polycytidylic (poly I:C) acid or Friend leukemia virus, and was decreased by mice pretreatment with cyclophosphamide or i-carrageenan. Treatment of "target" FLC with interferon suppressed the susceptibility of 745 FLC, but not that of 3Cl-8 FLC to host's NR. These data suggest that the "low" in vivo tumorigenicity of in vitro passaged FLC is, at least in part, due to host's NR directed against target structures associated with leukemia cells.
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PMID:Natural resistance in mice against Friend leukemia cells. I. Studies with in vitro passaged interferon-sensitive and interferon-resistant cell clones. 242 24

Interferons (IFNs), in addition to inducing an antiviral state in uninfected cells, are able to affect cell physiology, including cell differentiation. In this respect hematopoiesis is certainly the area in which most data have accumulated. In general IFN-alpha or -beta inhibit cell growth of normal progenitors of hematopoietic lineages. In leukemia cell cultures IFNs may either stimulate or inhibit cell growth and differentiation. We report here different biological effects of murine (mu) IFN-alpha 1, -beta, and -gamma species on the erythroid differentiation of dimethyl sulfoxide (DMSO)-induced Friend leukemia cells. Treatment with mu recombinant IFN-beta enhances DMSO-induced FLC differentiation, whereas treatment with IFN-alpha 1 species as well as with natural and recombinant mu IFN-gamma preparations only inhibits it. All these observed effects are neutralized by monoclonal antibodies against IFN-alpha, -beta, and -gamma species. When mu fibroblast IFN (a mixture of alpha and beta species) was used, the inhibitory effect attributable to IFN-alpha was partly overshadowed by the simultaneous presence of a majority of IFN-beta molecules exerting the opposite effect. This is in agreement with data obtained neutralizing fibroblast IFN preparations with excess amounts of monoclonal antibodies against IFN-beta (G.B. Rossi et al., 1988, "The Status of Differentiation Therapy of Cancer," Raven Press, New York) and with our previous reports indicating that mu fibroblast IFN can either enhance or inhibit DMSO-induced differentiation when administered at low (less than 500 U/ml) or high (greater than 5000 U/ml) doses, respectively. The inhibitory effect of IFN-alpha 1 on cell differentiation is not linked to any inhibitory effect on cell growth. Results obtained analyzing the effect of IFN-alpha 1 and -beta on various IFN-resistant FLC clones indicate that different mechanisms underlie the stimulatory effect of IFN-beta and the inhibitory effect of IFN-alpha 1. These results shed light on possibly distinct physiological roles of the various species of IFNs.
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PMID:Opposite effects of murine interferons on erythroid differentiation of Friend cells. 246 Sep 93

Experiments were designed to test the presence of antitumor natural resistance (NR) in DBA/2 mice against highly oncogenic in vivo passaged histocompatible Friend leukemia cells (FLC-V). NR was measured in vivo as rapid clearance of radiolabeled cells from different organs or as growth inhibition in lethally irradiated mice. Interferon-sensitive (745) or interferon-resistant (3C18) lines were used. Organ clearance studies showed that young recipients eliminate cells more rapidly than old mice. Moreover, depressive (e.g., cyclophosphamide or carrageenen) or enhancing (e.g., poly (I:C) or Friend leukemia virus infection) agents of NR function modulate accordingly leukemia cell clearance. Similar results were obtained testing tumor growth in lethally irradiated hosts, although modulating agents were substantially less effective in this system. Both FLC-745-V and FLC-3C18-V lines were equally susceptible to NR. Therefore, these data provide further support to the hypothesis that exogenous IFN capable of suppressing the growth of both lines could act via enhancement of the NR function.
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PMID:Natural resistance in mice against Friend leukemia cells. II. Studies with in vivo passaged interferon-sensitive and interferon-resistant cell clones. 246 1

Methyl 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboximidate (4) and ethyl 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidate (6) were synthesized and tested for antitumor and antiviral activity. A new facile synthesis of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride (5), starting with imidate 4, was also developed. The imidates 4 and 6 differed greatly in solubility and dosing requirements. Even so, both compounds exhibited significant activity in vivo against murine leukemia L1210. Nontoxic dosing with 4 also significantly diminished Friend leukemia induced splenomegaly. In contrast, neither imidate was active in vitro.
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PMID:Synthesis and antitumor activity of ribavirin imidates. A new facile synthesis of ribavirin amidine (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride). 273 79

The in vivo roles of the immunosurveillance mechanism of the host against leukemia induced by Friend leukemia virus (FLV) were examined. The significance of T-cells in host defense against FLV-induced leukemia was indicated by the fact that thymus-deprived C57BL/6N-nu/nu mice were sensitive to FLV, although normal C57BL/6N mice were, as already reported by many authors, resistant to FLV. In relation to the role of T-cells on the onset of FLV-induced leukemia, the population dynamics of the lymphocytic subpopulations of the systemic lymphoid organs after FLV injection in FLV-resistant C57BL/6N mice were examined in comparison with the dynamics in FLV-sensitive strains, C57BL/6N-nu/nu mice and normal C3H/HeN mice. In this system, Lyt-1+2- helper T-cells in the spleen of FLV-resistant C57BL/6N mice increased in number after FLV injection. The number of immunoglobulin positive cells did not remarkably change in FLV-resistant C57BL/6N mice after FLV injection, whereas the number increased in the lymph node of FLV-sensitive C3H/HeN mice. The results indicated that a major contribution to the relative susceptibility and resistance of the host to FLV was controlled by the capacity to mobilize T-cells to the spleen in an early stage of disease, although the interaction of these T-cells with other immune cells may play an important role in mediating host resistance to FLV-induced disease.
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PMID:Dynamics of lymphocytic subpopulations in Friend leukemia virus-induced leukemia. 287 Aug 2

Effects of Friend leukemia virus (FLV) inoculation in F1 specific pathogen free (SPF) mice were examined. Resistance to FLV was dominantly inherited both in F1 hybrid mice (BDF1) (FLV-resistant & FLV-sensitive with polycythemia) and F1 hybrid mice (B6C3F1) (FLV-resistant & FLV-sensitive with anemia). But the population dynamics of the nucleated cell components of F1 mice after FLV inoculation differed from those of FLV-resistant inbred mice. A small number of mature erythroblasts appeared in the peripheral blood of BDF1 mice. In B6C3F1 mice, erythroblastosis with splenomegaly and polycythemia occurred. However, all of these findings in BDF1 and B6C3F1 mice regressed spontaneously. In F1 mice, FLV induced an intermediate reactive pattern of the two patterns that had been induced in the parental strains. The results indicate that FLV may induce leukemia with various degrees of differentiation, according to the genetic difference of the host.
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PMID:Effects of Friend leukemia virus (FLV) inoculation in F1 mice and differentiation of FLV-induced leukemia. 298 Jan 28


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