Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A combination of retinoic acid (RA) and human recombinant DNA-derived interferon-gamma (Hu-IFN-gamma) was tested with respect to the growth inhibitory action on several human mammary carcinoma cell lines (ZR-75.1, 734-B, MCF-7, and BT-20), a human lung carcinoma cell line (CCL-185), and a human laryngeal carcinoma cell line (HEP-2). The mammary carcinoma cell lines were all sensitive to Hu-IFN-gamma, and 2 of them (ZR-75.1 and 734-B) were also affected by RA. The combination of both substances led to a pronounced synergistic amplification of growth inhibition in ZR-75.1 and 734-B cells. RA also increased the antiproliferative activity of Hu-IFN-gamma in the RA-resistant BT-20 cells and to a less pronounced degree in MCF-7 cells. In contrast to these findings, no synergistic effects were observed between Hu-IFN-gamma and RA in CCL-185 and HEP-2 cells. Human recombinant DNA-derived interferon-alpha 2 amplified the action of RA only in BT-20 cells, but it did not act synergistically with RA in the other cell lines tested.
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PMID:Synergistic antiproliferative effect of human recombinant interferons and retinoic acid in cultured breast cancer cells. 309 46

Peripheral blood lymphocytes from healthy donors (PBL) poorly lyse lung carcinoma cell lines A-549, A-427 and SK- MES-1 when tested in a short-term chromium release assay. When PBL are preincubated with human beta-interferon (IFN-beta), these cell lines are lysed with an efficacy comparable to that of erythroleukemia K-562 cells, the standard targets used in natural killer cell assays. However, when PBL are preincubated with gamma-interferon (IFN-gamma) instead, lysis of the lung carcinoma lines is little augmented. Unlabeled lung carcinoma A-549 cells block chromium release from labeled K-562 cells with non-boosted and IFN-gamma or IFN-beta-boosted effector cells. Also with the IFN-beta treated effectors, chromium release from A-549 targets is inhibited by unlabeled K-562 cells. Therefore, cells that lyse K-562 cells must be able to recognize A-549 cells, and, in the case of IFN-beta pretreated effectors, cause the killing of these cells as well. Data obtained with effector cells separated on discontinuous Percoll gradients also indicate that the same cells that lyse A-549 cells are responsible for lysis of K-562 cells. We conclude that in response to IFN-beta, effector cells previously able to lyse K-562, but unable to lyse A-549 targets, mature into fully competent killer cells capable of lysing tumor cells from lymphoid as well as from lung cancer origin. This effect is not elicited by IFN-gamma, indicating that killer cells respond differently to both interferon types.
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PMID:Differential effects of beta- and gamma-interferons on natural killer cell-mediated lysis of lung carcinoma cells. 311 53

Nocardia delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, injected i.p. in an oil/water emulsion to F6 rhabdomyosarcoma-bearing rats, inhibited the development of pulmonary metastases; 6 out of 10 rats were protected. Repeated i.p. administration of emulsified NDCM and of two other compounds, a Nocardia water soluble mitogen (NWSM a hydrosoluble fraction) and purified cell walls (CW, an insoluble macromolecular fraction) in Lewis lung carcinoma (LLC)-bearing mice resulted in a significant reduction of lung metastases. The efficiency of these fractions was enhanced by association with monokines. A combination regimen of NDCM, NWSM, and CW (100 micrograms/0.1 ml) and monokines (0.1 ml), injected i.p. in LLC-bearing mice, yielded a greater antimetastatic effect than either therapy alone. Peritoneal macrophages from mice which had been injected i.p. with NWSM or CW, when triggered either by TPA (tetradecanoyl phorbol acetate) or by zymosan, released large quantities of hydrogen peroxide and had a high rate of glucose consumption. These macrophages were activated as judged by their cytostatic activity against syngeneic P815 mastocytoma growth; they expressed biochemical markers which have been reported to characterize the activated state. Incubation of thioglycollate-elicited peritoneal macrophages with NWSM, and monokines for 72 h resulted in a cytotoxic activity against labeled LLC cells; addition of macrophage activating factor significantly increased the cytotoxic capacity of these macrophages. In view of this we postulate that the antimetastatic effect of soluble and insoluble N. opaca fractions and monokines might be mediated by activated peritoneal macrophages.
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PMID:Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions. 311 66

The purpose of these studies was to examine the antiproliferative properties of 16 recombinant human IFN-alpha B/D hybrids against various human tumor lines of different histological origin and to determine whether any of the hybrid molecules possessed immunomodulating activity that could active antitumor properties in peripheral blood monocytes of normal donors. Hybrids with the B domain at the NH2 terminal end exhibited higher activity for antiviral activity and a higher level of direct antitumor antiproliferative activities as compared with hybrids with the D domain at the NH2 terminal end. The positive hybrids were directly cytostatic to melanoma, glioblastoma, renal carcinoma, colon carcinoma, and prostatic carcinoma cells. Tumor cell sensitivity to IFN-alpha hybrids was independent of sensitivity to IFN-gamma or to Adriamycin. The growth of a normal cell line (human embryo fibroblast) was unaffected by IFN-alpha hybrids but was completely arrested by Adriamycin. Some of the IFN-alpha hybrids were also cytostatic to mouse melanoma, lung carcinoma, and fibrosarcoma cell lines, albeit at lower levels than they were to human cells. The incubation of monocytes with IFN-alpha hybrids with the B domain at the NH2 terminal end was also associated with marked antitumor cytotoxicity. Kinetic studies, however, indicated that this activity was attributable to IFN-alpha carried on monocytes and acting directly on tumor cells. We conclude that recombinant human IFN-alpha B/D hybrids possess potent direct antiproliferative activity against a large variety of human tumor lines.
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PMID:Direct antiproliferative effects of recombinant human interferon-alpha B/D hybrids on human tumor cell lines. 382 90

Human lung carcinoma cells persistently infected with mumps virus (Pc-10/MpV) were lysed with human peripheral blood mononuclear leukocytes (PBML) obtained from seropositive donors who had anti-mumps virus-neutralizing antibody in their sera. This cellular cytotoxicity was due not to the cytotoxic T lymphocytes but mainly to the non-T, non-B cells, possibly related to natural killer (NK) cells. Moreover, it was concerned not with antibody against mumps virus antigens but with alpha-interferon (IFN-alpha) produced in the mixture of human PBML and Pc-10/MpV cells, since this cellular cytotoxicity was suppressed by anti-human IFN-alpha rabbit serum. Exogeneous IFN-alpha augmented the cytotoxicity of non-T, non-B cells, not T cells, for the uninfected Pc-10 cells. IFN-gamma that had been induced by heat-killed Listeria monocytogenes in PBML had the same capacity to augment NK activity did IFN-alpha.
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PMID:Enhancement of cytotoxicity of human peripheral blood lymphocytes by interferon. 616 78

Lewis lung carcinoma (LLC-LN7) tumors stimulate myelopoiesis and induce immunosuppressive granulocyte-macrophage (GM)-progenitor cells. Treating mice having palpable tumors with IL-12 enhanced the frequency of GM-progenitors and did not diminish GM-suppressor activity. Proliferation of splenic T-cells of tumor-bearers to Con-A or to anti-CD3 plus IL-2 was suppressed; this was not enhanced by IL-12 treatment. Also not stimulated was T-cell secretion of IL-2 in response to autologous tumor, or the intratumoral T-cell content. IL-12 slightly increased splenic IFN-gamma secretion, and increased cytotoxicity of lymph node (but not spleen) cells toward autologous tumor. In these tumor-bearing mice that were immune depressed as a result of GM-suppressor cells, immune modulatory effects of IL-12 were marginal and did not affect tumor size or metastasis.
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PMID:Ineffective immune enhancement by IL-12 in tumor-bearing mice whose immune depression is mediated by suppressive granulocyte-macrophage progenitor cells. 760 May 36

MxA is an IFN-induced human protein which is located in the cytoplasm of induced cells. MxA makes the cells resistant to infection by influenza and vesicular stomatitis viruses. In the present work we used baculovirus expression system to produce MxA protein. The protein was purified to homogeneity and highly specific polyclonal anti-MxA antibodies were prepared. In human mononuclear cells, and A549 lung carcinoma cells expression of MxA protein is induced by very low (< 1 IU/ml) doses of leukocyte IFN-alpha (nIFN-alpha), whereas IFN-gamma does not seem to induce it or potentiate the induction by IFN-alpha. In mononuclear cells stimulated with high doses of leukocyte IFN-alpha concentrations, the amount of MxA mRNA was induced 10-fold at 4 h after IFN induction and up to 10-fold higher MxA protein levels were observed at 24-48 h postinduction. The gene can be reinduced by IFN-alpha 24 h after the initial induction suggesting for a lack of negative feedback after this time point. The protein is very stable, the half-life being approximately 2.3 days. Flow cytometric analysis revealed that monocytes have higher basal and induced MxA protein levels than lymphocytes but the dose-dependency of MxA expression is very similar in both cell types. Granulocytes are producing very low amounts of MxA protein.
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PMID:Control of IFN-inducible MxA gene expression in human cells. 767 92

Production of granulocyte-macrophage (GM) colony-stimulating factor by murine metastatic Lewis lung carcinoma cells (LLC-LN7) increases the number and distribution of GM progenitor cells that are suppressive to T cell responsiveness to interleukin 2 (IL-2). The presence of these GM suppressor cells can be diminished by treatment of LLC-LN7-bearing mice with low doses of 100 units IFN-gamma plus 10 units tumor necrosis factor alpha (TNF-alpha). The aim of this study was to determine whether treatment of LLC-LN7-bearing mice with IFN-gamma/TNF-alpha to diminish GM suppressor cell presence would increase the responsiveness to IL-2 immune stimulatory therapy (100-1000 IU, twice daily for 5 days). Treatment first with IFN-gamma/TNF-alpha and then also with low dose IL-2 increased both the numbers of CD4+ and CD8+ cells within the tumor and the levels of their expression of the p55 IL-2 receptor. These intratumoral T cells also had an increased cytolytic capacity toward autologous tumor cells and an increased capacity to proliferate and secrete IL-2. Such effects were observed to a lesser extent in mice that were treated with either IFN-gamma/TNF-alpha alone or with low doses of IL-2 only. The combination treatment regimen of IFN-gamma/TNF-alpha and then IL-2 was also significantly more effective at reducing the size of the primary tumor and the formation of metastatic lung nodules than were the individual treatments. These results show that treatment to minimize the presence of GM suppressor cells enhances the effectiveness of IL-2 to stimulate anti-tumor immune responses and to diminish tumor growth and metastasis.
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PMID:Treating tumor-bearing mice with low-dose gamma-interferon plus tumor necrosis factor alpha to diminish immune suppressive granulocyte-macrophage progenitor cells increases responsiveness to interleukin 2 immunotherapy. 785 Aug 4

Metastatic Lewis lung carcinoma (LLC-LN7) cells have previously been shown to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) which induces the appearance of immunosuppressive granulocytic-macrophage progenitor cells (GM-suppressor cells). The present in vitro studies showed that treatment of LLC-LN7 tumor cells with 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] plus low dose gamma-interferon (IFN-gamma) resulted in a synergistic reduction in tumor GM-CSF secretion and a blockage in the capacity of the tumor cells to induce GM-suppressor cells. The production of GM-CSF by bulk cultures of enzymatically dissociated LLC-LN7 tumors that had been excised as s.c. tumors from mice was also blocked when the dissociated tumor was cultured with 1,25(OH)2D3 plus IFN-gamma. Our previous and present studies showed that GM-suppressor cells persist in bulk cultures of dissociated LLC-LN7 tumors after a 1-week period of culture. Addition of either 1,25(OH)2D3 or IFN-gamma did not diminish the persistence of GM-suppressor cells. However, when tumor production of GM-CSF was inhibited by culture with both 1,25(OH)2D3 and IFN-gamma, the ability of the dissociated tumor culture to sustain the presence of GM-suppressor cells was blocked. This elimination of GM-suppressor cells by treatment of the dissociated tumor with 1,25(OH)2D3 and IFN-gamma coincided with increased expansion of CD8+ tumor-infiltrating leukocytes and increased cytotoxic T-lymphocytes activity of tumor-infiltrating lymphocytes. These results suggest that blocking tumor production of GM-CSF can interrupt the suppressor-inducing cascade of the tumor and enhance expansion and anti-tumor cytolytic reactivity of tumor-infiltrating leukocytes.
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PMID:1 alpha,25-dihydroxyvitamin D3 plus gamma-interferon blocks lung tumor production of granulocyte-macrophage colony-stimulating factor and induction of immunosuppressor cells. 826 14

We studied the effects of pharmacologically attainable concentrations of interferon-alpha (IFN-alpha) and gamma (IFN-gamma) on the growth of cells incubated under hypoxic conditions (2% O2; approximately 14 mm Hg partial pressure) or exposed to oxygen at atmospheric pressure (21% O2; approximately 147 mm Hg). The cells were from four IFN-sensitive lines: A-549 lung carcinoma and G-361 human melanoma cells grow better under hypoxic conditions, but the growth of Hep-2 laryngeal carcinoma and WISH amnion cells is not affected by the environmental oxygen tension. The antiproliferative effects of the IFN were assessed in terms of cell cloning efficiency and also from the number of cells, relative to controls, measured 1, 2, and 3 days after seeding. Under hypoxic conditions, the cloning efficiency of A-549 and G-361 cells was increased, and they became significantly less responsive to the antiproliferative effect of IFN, and especially of IFN-gamma. No such effects were seen with WISH or Hep-2 cells. Hypoxic conditions are found in the necrotic areas present in most solid tumors, and our results suggest that these may decrease the antiproliferative effects of IFN. They may in part explain why IFNs have so little antitumor activity in such tumors, and they also suggest methods that may increase this activity.
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PMID:Effects of hypoxia on the antiproliferative activity of human interferons. 859 Mar 17


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