Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human T-T hybridoma clone with helper cell phenotype was established from fusions between a HPRT- variant of the human T-cell lymphoma Molt4, and PPD-activated normal human T-lymphocytes. The hybrid clone (MP-6) was characterized with regard to expression of markers and lymphokine secretion. The T-T hybridoma was positive for Leu 3a, and thus of T-helper cell lineage. The transferrin receptor (T-9) and the interleukin 2 (IL-2) receptor (Tac) were also expressed as judged by immunofluorescence analysis using monoclonal antibodies. The hybridoma produces B-cell stimulatory factor (BSF) with proliferation and maturation activities, growth inhibitory factor (GIF), leukocyte migration inhibitory factor (LIF) constitutively under serum free conditions, but no detectable interferons (IFN-alpha, IFN-beta, IFN-delta), nor interleukin 2 (IL-2). Weak interleukin 1 (IL-1)-like activity was found. The B-cell stimulatory factor (BSF) induced solid phase-anti-mu triggered resting B-cells obtained from human spleen, tonsil or peripheral blood to proliferate and to secrete IgM and IgG. Without anti-mu triggering the BSF had no proliferation inducing effect. The BSF was characterized and partially purified using ammonium sulphate precipitation, Blue-Sepharose, HPLC hydrophobic interaction and HPLC gel filtration chromatography. The BSF was heat labile at 56 degrees C and was present in two forms, one with high and one with intermediate hydrophobicity. The more hydrophobic form of BSF has a molecular weight of 12K-14K. Kinetic studies of the lymphokine secretion revealed that BSF was produced in detectable amounts in low density (0, 2 X 10(6) cells/ml) 18-24 h cultures. In 48 h to 72 h cultures there was a significant influence of growth inhibitory activities (GIF) produced. GIF, with an apparent MW of 90K could be absorbed out on certain tumor cell lines or on Blue-Sepharose. Further absorption analysis of BSF activities show that anti-mu triggered B-cells but neither resting B-cells nor T-cells could absorb BSF activity.
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PMID:A T-helper cell x Molt4 human hybridoma constitutively producing B-cell stimulatory and inhibitory factors. 294 47

IFN-alpha induces tumor regression with a high percentage of complete remissions in hairy cell leukemia. We have recently reported that hairy cells express specific IFN-alpha receptors which are down-regulated upon therapy. We show here that the activity of 2-5 A synthetase, an IFN-induced enzyme, is 2 to 7-fold stimulated in hairy cells from responsive patients within 12-24 h after the first IFN dose. This in-vivo enzyme induction paralleled the kinetics of receptor down-regulation. In one patient who was unresponsive to IFN-alpha treatment neither expression of IFN-alpha receptor nor change in 2-5 A synthetase were expressed and modulated as in sensitive patients. In-vitro treatment of hairy cells with recombinant interferons showed that IFN-beta 1 was able to induce this enzyme to the same extent than IFN-alpha 2, whereas IFN-gamma was inactive despite the presence of specific IFN-gamma receptors. Our results indicate that IFN-alpha can exert its therapeutic effects by acting directly on the hairy cells through interaction with surface membrane receptors. Induction of 2-5 A synthetase can be one of the steps involved in this action. However, both mechanisms, as well as receptor down-regulation are not sufficient to explain the responsiveness of hairy cell leukemia to IFN-alpha.
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PMID:Action of interferon-alpha on hairy cell leukemia: expression of specific receptors and (2'-5')oligo (A) synthetase in tumor cells from sensitive and resistant patients. 296 76

We studied the enhancement of cytolytic activity of T3- natural killer cell-derived clones, of T3+ T cell activated killer (AK) clones, and of fresh peripheral blood lymphocytes (PBL) by various crude and recombinant interferon (r-IFN) as well as IL 2 preparations. It was found that IFN-beta had the highest cytotoxicity inducing potency as compared to crude or r-IFN-alpha or -gamma preparations. This enhancement was blocked by anti-IFN-beta antibodies but not by anti-IFN-gamma antibodies. IL 2 also strongly enhances cytolytic activity in cloned T3- killer cells that express the IL 2 receptors as determined with the anti-Tac monoclonal antibody (MAb) at concentrations of IL 2 (25 U/ml) which induced one-half of the maximal proliferation capacity in human T cells and murine CTLL cells. For enhancement of cytolytic activity in fresh NK cells, a much higher concentration of IL 2 is required. In addition, the enhancement of cytolytic activity by r-IL 2 but not that by IFN-beta can be reduced by anti-Tac MAb, suggesting that the IL 2 receptor is involved in the enhancement by IL 2, but not by IFN. Both IFN-beta and IL 2 were able to enhance (over threefold) the cytolytic activity of T3- cloned killer cells against a variety of tumor target cell types. Another remarkable observation was that K562 cells, the most commonly used target cell for determining NK cell cytolytic activity, are not the most suitable targets to assess enhancement of nonspecific lytic activity as compared to Daudi or lung tumor-derived cell lines. No enhancement of anti-body-dependent cellular cytotoxicity was observed. Finally, the effects of these biological response modifiers were much more pronounced on "fresh" and cloned T3- natural killer cell-derived than on T3+-activated killer mature T cell-derived clones.
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PMID:Interferon-beta and recombinant IL 2 can both enhance, but by different pathways, the nonspecific cytolytic potential of T3- natural killer cell-derived clones rather than that of T3+ clones. 300 99

Incubation of several human tumor cell lines with human interferon-gamma (IFN-gamma) increased the specific binding of subsequently added 125I-labeled recombinant human tumor necrosis factor (TNF). A similar increase in TNF binding was seen in murine L929 cells after incubation with murine IFN-gamma, but not after incubation with human IFN-gamma. Increased TNF binding to cells incubated with IFN-gamma was due to an increase in the number of TNF receptors, with no demonstrable change in binding affinity. In one out of two human cell lines tested, IFN-alpha and IFN-beta also produced increased TNF binding, albeit with a lower efficacy than IFN-gamma. A maximal increase in TNF binding was seen after about 6 to 12 hr of incubation with IFN. Increased TNF binding due to enhanced TNF receptor expression may contribute to the enhancement of TNF cytotoxicity seen in some tumor cell lines after INF treatment. Modulation of TNF receptor expression by IFN may also influence other biological activities of TNF.
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PMID:Interferon-gamma enhances expression of cellular receptors for tumor necrosis factor. 300 10

The secretion of interferon (IFN)-gamma by T lymphocytes is mediated by the synthesis of interleukin 2 (IL-2) and the availability of IL-2 receptors. Since some Burkitt's lymphoma lines express Tac antigen and can be triggered to secrete IL-2 following activation with the new tumor promoter teleocidin, we addressed the question of whether the induction of IL-2 by B lymphocytes is accompanied by the induction of IFN-gamma. IFN-gamma has not been detected in any of the 25 cell lines studied, and following stimulation with teleocidin, we triggered the synthesis of IFN-gamma in JLP(C), a pre-Burkitt's cell line. The mechanism of IFN-gamma secretion by B lymphocytes is not clear. Our findings demonstrate that the synthesis of IL-2 by B cells is not accompanied by IFN-gamma and suggest that the synthesis of IFN-gamma is not mediated by IL-2 or IL-1 or B-cell growth factor. Neutralization studies have shown that IFN-gamma secretion is not accompanied by the induction of IFN-alpha or IFN-beta. Our data imply that B cells can be triggered to secrete IFN-gamma under certain circumstances. Whether similar function occurs in vivo is not known.
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PMID:Burkitt's cells can be triggered by teleocidin to secrete interferon-gamma. 301 Jul 6

The footpad swelling reaction induced by local injection of S. marcescens lipopolysaccharide was found to be inhibited in mice given a transplantable tumor (TA3) or cell-free ascitic fluid from tumor-bearing mice. The tumor was shown to contain LDH virus, which is known to cause inapparent persistent infections in mice. Monoclonal antibodies directed against protein VP3 of the LDH virus could partially abrogate the anti-inflammatory effect of the TA3-ascitic fluid, and, conversely, the anti-inflammatory effect could be obtained by LDH virus isolated from the tumor and reproduced by serial passage of cell-free fluids. Inhibition of the footpad reaction was seen in the acute but not in the chronic phase of LDH virus infection, suggesting that the anti-inflammatory effect might be due to endogenous interferon (IFN) which, similarly, was only detectable in the acute phase. Newcastle disease virus, another potent interferon inducer, had a similar inhibitory effect on the footpad reactivity. Moreover, the inhibitory effect of LDH virus infection could partially be abrogated by administration of a polyclonal antibody directed against murine IFN-alpha,beta. Finally, passively administered natural murine IFN-alpha,beta or recombinant murine IFN-alpha 1 (but not recombinant murine IFN-beta) was found to cause inhibition of the footpad reaction. Since Gram-negative bacteria and their lipopolysaccharides have the ability to induce a systemic interferon response, our findings suggest that this interferon may play a modulatory role in local inflammation caused by these bacteria. Our findings also open a new perspective for interferon therapy of certain inflammatory reactions to bacterial infections.
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PMID:The inhibition of endotoxin-induced local inflammation by LDH virus or LDH virus-infected tumors is mediated by interferon. 303 82

Freshly isolated human peripheral blood monocytes from healthy volunteers were not cytotoxic to allogeneic A375 melanoma cells, but they were activated to the cytotoxic state by incubation in vitro with either des-methyl muramyl dipeptide (norMDP; minimal effective dose, 0.5 micrograms/ml) or recombinant human interferon-gamma (rIFN-gamma; minimal effective dose, 1 U/ml). A combination of subthreshold concentrations of these agents (norMDP, 0.5 micrograms/ml; rIFN-gamma, 10 U/ml) also induced significant cytotoxicity, indicating that the effects of norMDP and rIFN-gamma in monocyte activation are synergistic. Natural human IFN-gamma (nIFN-gamma) and norMDP also had similar synergistic effects. Pretreatment of rIFN-gamma with anti-IFN-gamma antibody completely inhibited its synergistic effect with norMDP in monocyte activation. Because pretreatment of rIFN-gamma and norMDP with polymyxin B did not interfere with their effects in monocyte activation, the preparations were not contaminated with lipopolysaccharide. Moreover, because pretreatment of monocyte monolayers with anti-Leu-11b antibody (anti-natural killer (NK) cell antibody) and complement did not interfere with the synergistic effects of norMDP and rIFN-gamma, whereas pretreatment with anti-Leu-M1 antibody (anti-monocyte antibody) caused complete inhibition of their effects, the observed tumor cytotoxicity of monocyte-rich monolayers was probably not due to a small number of adherent NK cells, but to the stimulation of the monocytes. Natural and recombinant IFN-alpha and IFN-beta at concentrations of greater than or equal to 100 U/ml also induced tumoricidal activity of monocytes, but unlike IFN-gamma, their effects were additive with norMDP, and they had less priming effect than IFN-gamma when they were added before norMDP to monocytes. These findings suggest that recombinant human IFN-gamma has much more synergistic potential with norMDP than IFN-alpha or IFN-beta, and this synergism of rIFN-gamma and norMDP for monocyte activation could be of clinical value in treatment of disseminated malignant diseases, because these compounds are readily available at standardized concentrations.
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PMID:Comparative analysis of the priming effect of human interferon-gamma, -alpha, and -beta on synergism with muramyl dipeptide analog for anti-tumor expression of human blood monocytes. 307 97

Human TNF was detected fairly recently and at present the anti-tumor activity of human recombinant TNF is being examined against various malignant tumors of human origin. In the present study, we report the anti-tumor activity of recombinant human TNF against human malignant glioma cell lines in vitro and in vivo, in addition to its combined effects with HuIFN-beta. The in vitro study was conducted as follows. Thirteen human glioma cell lines were exposed to 100 U/ml TNF, 1,000 IU/ml HuIFN-beta, or both, and the suppression rate was calculated on days 3, 5 and 7. In the in vivo study, nude mice carrying a human glioma cell line, KMS II, in the subcutaneous tissues were divided into groups and drugs were administered intratumorally as described below. 1) control, 2) TNF 5,000 U single administration, 3) TNF 5,000 U, intermittently administered (once/week for two weeks), 4) TNF 5,000 U, continuously administered (3/week for two weeks), 5) HuIFN-beta 50 X 10(4) IU (3/week for two weeks), and 6) combination of 4) with 5). Results of the in vitro study revealed some suppressive effects on proliferation of tumor cells on day 7 in all 13 glioma cell lines examined with 100 U/ml TNF. And also, especially in 8 of 13 cell lines, the suppression rate was more than 30%. The suppressive effects of TNF were augmented by combined use of HuIFN-beta in all cell lines, giving a range of suppression of 67.8 to 99.3%. The in vivo study revealed that the mean tumor weight ratios (control = 100%) on day 19 (the end of the experiment) were as follows; single administration of TNF: 41.3%, intermittent: 46.7%, continuous: 26.7%, HuIFN-beta: 65.9%, combination: 18.5%. Statistical analysis disclosed significant suppressive effects on tumor proliferation between the control group and 3 TNF-administered groups (single, intermittent, and continuous) and that suppression in the continuously administered group was more severe in comparison with the group given single administration. Moreover, it was suggested that combination therapy with TNF and Hu IFN-beta was more effective than a single therapy with TNF only or HuIFN-beta only. From the results described above, it was found that human recombinant TNF had some cytotoxic effects against human malignant gliomas in vitro and in vivo, although the degree of cytotoxicity was not always higher in comparison with the effects of TNF.
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PMID:[Anti-tumor activity of human recombinant TNF against human malignant glioma cell lines and combined effect with Hu INF-beta]. 308 96

Freshly isolated human peripheral blood monocytes from healthy volunteers are not cytotoxic to allogeneic A375 melanoma cells, but they were rendered tumoricidal by incubation in vitro with either liposomes containing 5 micrograms/mumol phospholipid of muramyl tripeptide phosphatidylethanolamine (liposome-MTP-PE; optimal dose, 500 nmol/ml) or recombinant human interferon gamma (rIFN-gamma; optimal dose, 100 U/ml). A combination of sub-threshold concentrations of liposome-MTP-PE (50 nmol/ml) and rIFN-gamma (1 or 10 U/ml) also induced significant tumor-cell killing, indicating that the effects of rIFN-gamma and liposome-MTP-PE in monocyte activation are synergistic. In contrast to rIFN-gamma, recombinant IFN-alpha and IFN-beta had additive effects with liposome-MTP-PE in human monocyte activation. Since recombinant human IFN-gamma has a synergistic effect with liposome-MTP-PE in monocyte activation, unlike IFN-alpha or IFN-beta, and liposome-MTP-PE as well as rIFN-gamma is available at standardized concentrations, this combination could be of clinical value in the treatment of disseminated malignant disease.
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PMID:Synergism of recombinant human interferon gamma with liposome-encapsulated muramyl tripeptide in activation of the tumoricidal properties of human monocytes. 309 90

The suppressive effect of IFN-alpha and IFN-beta on the induction of tumoricidal activity in mouse bone marrow-derived macrophages was investigated. Macrophages incubated for 24 hr with IFN-beta developed lower levels of cytolytic activity when stimulated with IFN-gamma and LPS, in comparison with macrophages pretreated with medium. The suppressive effect was dependent on the pretreatment dose of IFN-beta over a concentration range of 1 to 1,000 U/ml. Analysis of IFN-gamma dose response curves of IFN-beta treated macrophages showed that these cells were less sensitive to IFN-gamma. The suppressive effects were fully neutralized by an antiserum to IFN-alpha/beta. Prostaglandins were apparently not involved in this process since the addition of indomethacin to IFN-beta treated macrophages did not prevent the loss of responsiveness to activating stimuli. In contrast to the results obtained with IFN-alpha and IFN-beta, macrophages pretreated with IFN-gamma did not develop lower levels of cytolytic activity when again stimulated with IFN-gamma and LPS. These observations provide evidence for a potentially important negative regulatory role for IFN-alpha and IFN-beta in macrophage activation for tumor cell killing.
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PMID:Suppressive effect of interferon-beta on development of tumoricidal activity in mouse macrophages. 310 17


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