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)

Interleukin-4 (IL-4) is a cytokine, with potential anti-neoplastic effects. This study examined the effects of IL-4 on host anti-tumor responses in a murine model. C57/B16 mice (n = 40) were randomized to receive Lewis lung carcinoma (10(6) cells: right flank; sc) or saline, and sacrificed 10 days postinoculation for assessment of peritoneal macrophage (PMO) anti-tumor mechanisms [superoxide anion generation (O2-), tumor necrosis factor (TNF), and TNF-independent (P815) cytotoxicity], splenocyte mixed lymphocyte response (MLR) (Balb/c stimulator), and cytotoxic lymphocyte generation (CTL against P815). Cells were cultured +/- IL-4 (100 U/ml). In a second study, 20 mice received Lewis lung implants (sc) and were randomized on Day 21 to receive daily IL-4 (1000 U/mouse; ip) or saline. Tumor volumes and median survival were assessed. Tumor necrosis factor-independent cytotoxicity (O2-, MLR and CTL) was impaired in the tumor-bearing (TB) study group. Interleukin-4 administered to cultured cells from TB mice enhanced O2-, as well as MLR and CTL (P less than 0.01), and decreased TNF release but did not alter PM phi TNF-independent anti-tumor responses (P815). In vivo administration of IL-4 significantly decreased tumor growth (P less than 0.05) after 10 days of treatment and significantly prolonged median host survival (P less than 0.05). These findings indicate the therapeutic potential of IL-4 in the TB host which may function through downregulation of TNF production while potentiating certain T cell-dependent and independent anti-tumor immune mechanisms.
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PMID:Anti-neoplastic effects of interleukin-4. 131 83

The effects of the i.v. administration of endotoxin (6.25-50 micrograms/mouse on day 13 after tumor implantation) in mice treated orally with lysozyme hydrochloride (100 mg/kg on days 5-12 from tumor implantation) were examined using Lewis lung carcinoma in the C57Bl mouse and MCa mammary carcinoma of CBA mice. On primary tumor growth, endotoxin alone causes a dose-dependent and statistically significant reduction with a nadir on day +2 from endotoxin treatment. Combined with lysozyme, endotoxin causes an effect independent of the dose used, corresponding to the effect caused by endotoxin alone at the dose of 25 micrograms/mouse. No tumor regression was recorded in any of the treated groups. Endotoxin is virtually devoid of effects at the metastatic level. In the same conditions, lysozyme causes a reduction of primary tumor growth and a more pronounced inhibition of lung metastasis formation as expected from its already reported effects. The antitumor activity of endotoxin, unlike lysozyme, can be ascribed to tumor hemorrhagic necrosis due to tumor necrosis factor (TNF) production, as determined in tumor homogenates. Endotoxin does not increase the antitumor effects in mice treated with lysozyme, as expected from the data obtained with the more immunogenic SA1 sarcoma, although lysozyme increased the mitogenic response to ConA of ex vivo isolated splenocytes, in vitro cultured in the presence of IL-2.
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PMID:Effects of endotoxin in mice bearing solid metastasizing tumors and treated with lysozyme hydrochloride. 140 79

We have identified two lung carcinoma cell lines, A549 and Calu-1, expressing low levels of the macrophage colony-stimulating factor (CSF-1) receptor (CSF-1R), encoded by the c-fms oncogene. The effect of CSF-1 on the invasive potential of these CSF-1R-positive tumor cell lines and on two other CSF-1R-bearing cell lines, the BT-20 breast carcinoma cell line and the CSF-1 growth-dependent murine macrophage cell line BAC1.2F5, was examined using a human amnionic basement membrane invasion model. Culture of A549, Calu-1, and BAC1.2F5 cells with CSF-1 (250 ng/ml) resulted in a maximal 12-, 5-, and 12-fold enhancement of invasion, respectively, compared to control cells cultured in medium alone. Larger concentrations of CSF-1 (750 ng/ml) reduced A549 and Calu-1 invasiveness compared to the effect of the 250-ng/ml dose. Maximal enhancement in invasion of A549 and Calu-1 cells occurred after a 24- and 48-h exposure to CSF-1, respectively. CSF-1 increased invasiveness 6-fold in BT-20 cells induced by glucocorticoids to express high levels of CSF-1R, in comparison to control cells not exposed to glucocorticoids or CSF-1. In contrast, CSF-1 had no effect on invasion in the CSF-1R-negative MCF-7 cell line. Culture of A549 and Calu-1 cells with other cytokines and growth factors including GM-CSF (500 units/ml), IL-3 (1 ng/ml), interferon-gamma (500 units/ml), and tumor necrosis factor (50 units/ml) had no significant effect on invasiveness. Thus, CSF-1 increases invasiveness in CSF-1R-positive tumor cell lines, suggesting a role in enhancing the metastatic potential of tumor cells expressing the CSF-1R.
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PMID:Macrophage colony-stimulating factor (CSF-1) enhances invasiveness in CSF-1 receptor-positive carcinoma cell lines. 153 51

Nicotinamide methyltransferase (Nmd CH3transferase) activity increased in the liver of mice after i.p. transplantation of Ehrlich ascites tumor (ascitic form), but not in the liver of mice with acute inflammation induced by the i.p. administration of D-galactosamine, and it rather showed a decrease together with necrosis after carbon tetrachloride administration. When Nmd CH3transferase activity of rat hepatocytes in primary culture was investigated with the addition of dexamethasone, epidermal growth factor, transforming growth factor-beta, tumor necrosis factor-alpha and N1-methylnicotinamide (1-CH3Nmd), changes in activity were not correlated with DNA synthesis, suggesting that the increase of this enzyme activity in the tumor host liver was not directly related to liver cell proliferation. Thus, in order to make use of the increase of this enzyme activity as a tumor burden marker, a procedure for its estimation by measuring the blood level of 1-CH3Nmd, a metabolite of Nmd produced by Nmd CH3transferase, was established. The 1-CH3Nmd level in the blood of mice bearing Ehrlich ascites tumor 4 h after s.c. loading of Nmd (500 mg/kg body weight) was closely correlated with this enzyme activity in the liver (r = 0.835, P less than 0.00001) from the early to the terminal stage of tumor development. Furthermore, similar correlations were seen in the animal groups bearing various other tumors, such as s.c. implanted Ehrlich ascites tumor (solid form) and i.p. implanted sarcoma S-180, hepatoma MH-134, Yoshida ascites sarcoma and leukemia L-1210, but not solid tumors such as Lewis lung carcinoma and melanoma B-16, although almost all of the animals bearing these tumors showed a higher enzyme activity than their control normal animals.
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PMID:N1-methylnicotinamide level in the blood after nicotinamide loading as further evidence for malignant tumor burden. 183 57

The effect of short wave length ultraviolet C (UVC) light irradiation on tumor cell immunogenicity and sensitivity to natural cell-mediated cytotoxicity was studied. Two consecutive courses of UVC irradiation of 3LL Lewis lung carcinoma and MCA105 fibrosarcoma increased their immunogenicity and sensitivity to lysis by normal spleen cells. Analysis of the effector cells involved in lysis of the parental MCA105 and UV-treated MCA105UV tumor cells was performed by comparing the cytotoxic activity of normal spleen cells containing both natural killer (NK) and natural cytotoxicity (NC) cell activity (NK+, NC+) with: (a) normal spleen cells in which NC activity was neutralized by anti-tumor necrosis factor (TNF) antibodies (NK+, NC-); (b) NK-depleted or NK-deficient spleen cells (NK-, NC+); and (c) NK-depleted or -deficient spleen cells with NC activity blocked by anti-TNF antibodies (NK-, NC-). In addition, the ability of polyinosinic-polycytidylic acid or interleukin 2-stimulated spleen cells to lyse UV-treated and untreated tumor cells in the presence or absence of anti-TNF antibodies was also investigated. Lysis of MCA105 cells was shown to be mediated mostly by NC cells, since it was inhibited in the presence of anti-TNF antibodies and was not significantly affected by depletion or stimulation of NK cells. UV irradiation of MCA105 tumor cells substantially increased their sensitivity to both NK and NC effector cells. Augmentation of NK sensitivity of MCA105UV cells was associated with an increase in their lysability by large granular lymphocyte-derived cytolytic granules. UVC treatment of tumor cells also increased their sensitivity to lysis by recombinant TNF-alpha, pointing to the possible mechanism responsible for the increase in their sensitivity to NC cell-mediated cytotoxicity. Indeed, selection of MCA105UV cells for resistance to TNF led to resistance to spleen cell-mediated NC cytotoxicity. UVC irradiation did not affect internalization and degradation of TNF by MCA105UV cells but substantially increased sensitivity to TNF-induced DNA fragmentation. The results of this study indicate that UV irradiation can be a potent and stable modulator of the immunobiological properties of tumor cells.
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PMID:Increase in immunogenicity and sensitivity to natural cell-mediated cytotoxicity following in vitro exposure of MCA105 tumor cells to ultraviolet radiation. 191 41

We have shown the in vivo usefulness of a novel chimera tumor necrosis factor (TNF), called rTNF-STH, which was constituted with human thymosin beta 4 and recombinant human TNF-SAM1. Tumor necrosis was induced by intravenous injection of a smaller amount of rTNF-STH (1 x 10(3) U/mouse, 0.67 microgram/mouse) than rTNF-alpha or rTNF-S (1 x 10(4) U/mouse, 2.5-5 micrograms/mouse). Significant antitumor effects of rTNF-STH to Meth A fibrosarcoma, B16 melanoma, MH134 hepatoma, or Lewis lung carcinoma (3LL) were observed by systemic injection of rTNF-STH at the maximum tolerable dose of 1 x 10(4) U/mouse (6.7 micrograms/mouse); this dose did not cause regression of tumors by conventional rTNF-alpha. rTNF-STH showed a significant prolongation of its half-life in serum. The average calculated half-life of the chimera protein is about 110 min, which is 15 times longer than that of original TNF-SAM1 (7.5 min). On the basis of this prolongation of half-life of rTNF-STH and its efficient hemorrhagic necrotic activity, the antitumor effect of rTNF-STH--as compared with that of the known TNF species--is discussed. Findings indicate that use of the chimera protein to alter the N-terminal region of TNF may be a promising approach to obtain molecules that more favorably attack tumors and other diseases than conventional rTNFs.
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PMID:Antitumor activity of a novel chimera tumor necrosis factor (TNF-STH) constructed by connecting rTNF-S with thymosin beta 4 against murine syngeneic tumors. 204 90

A variety of biologic and synthetic agents protect BALB/c mice against experimental M109 micrometastases. We have presented evidence that eradication of these metastases is mediated by the activation of host macrophages to the tumoricidal state. We now present evidence that injection of H22, a neutralizing hamster IgG monoclonal antibody to murine interferon-gamma (IFN-gamma; macrophage activating factor), 2 days prior to i.v. tumor inoculation markedly increases the metastatic capacity of M109 lung carcinoma cells. Therefore, we tested several cytokines that induce or mediate macrophage-mediated cytotoxicity, including IFN-gamma, tumor necrosis factor-alpha, and interleukin-1 beta (IL-1 beta), for their ability to inhibit the development of experimental M109 lung metastases. Intraperitoneal treatment with recombinant murine (rMu) IFN-gamma (greater than or equal to 10,000 units/mouse) or recombinant murine TNF-alpha (greater than or equal to 10,000 units/mouse) produced greater than 60% inhibition of metastasis formation. Optimal therapy was observed when cytokines were administered 2 days prior to i.v. tumor cell inoculation. Neither IFN-gamma nor TNF-alpha inhibited colony formation of M109 cells in vitro, suggesting a host-mediated mechanism for antitumor activity. Peritoneal macrophages were primed for tumor cytotoxicity by treatment with either IFN-gamma or TNF-alpha. Intraperitoneal treatment with recombinant human IL-1 beta (1 X 10(5) units) lacked antimetastatic activity. The results further support the role of activated macrophages in the destruction of M109 micrometastases.
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PMID:Protective activity of recombinant murine tumor necrosis factor-alpha and interferon-gamma against experimental murine lung carcinoma metastases. 211 56

We have studied the short- and long-term effects of human recombinant tumor necrosis factor (TNF) and TNF/recombinant human interferon-gamma (IFN-gamma) mixtures on A549 human lung carcinoma cells maintained in organotypic culture. Continuous treatments with 2 x 10; 2 x 10(2); 2 x 10(3) and 2 x 10(4) U/ml TNF or with mixtures of TNF/IFN-gamma at 2 x 10(2) and 10(3) U/ml, respectively, were administered. Nodule growth, cell proliferation and cell survival were studied. On the 2nd day of treatment with TNF, only the highest dose (2 x 10(4) U/ml) diminished cell proliferation significantly, as measured by tritiated thymidine uptake into DNA. On the 10th day, only the lowest TNF dose (2 x 10 U/ml) induced no significant growth inhibition. Necrosis and nodule disintegration were apparent in the 2 x 10(4) U/ml-treated nodules where DNA synthesis decreased. In this case, using agar cloning assays, no cell survival could be observed. Similar results could be obtained with TNF at low concentration (2 x 10(2) U/ml) in combination with INF-gamma (10(3) U/ml), showing a synergistic effect on inhibition of cell proliferation. In the long-term experiments, with the lower TNF doses, in situ evidence of regrowth was observed (outgrowing zones in the nodules) on about the 40th day of treatment, and nodule recovery was confirmed by the resumption of DNA synthesis measured on the 50th day of treatment. No regrowth, however, occurred when the IFN-gamma/TNF combination was used, and the nodules disintegrated completely on the 35th day of treatment without evidence of any cellular survival.
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PMID:Short- and long-term synergistic effects of human tumor necrosis factor and interferon-gamma on A549 human lung cancer cells maintained in three-dimensional culture. 211 52

In order to investigate the antitumor effect of recombinant human interleukin-1 beta (IL-1 beta) alone and in combination with natural human tumor necrosis factor-alpha (nHuTNF-alpha), we used female BDF1 mice bearing Lewis lung carcinoma (3LL). IL-1 beta showed an antiproliferative effect against pulmonary metastatic tumors of 3LL in a dose-dependent manner. We observed 19.6 +/- 6.6, 18.6 +/- 5.3, 14.1 +/- 4.4 and 13.0 +/- 6.0 metastatic tumors at doses of 0.5, 1.0, 2.5 and 5.0 micrograms IL-1 beta/mouse/day by daily intravenous administration (the number of metastatic tumors of the control group was 26.3 +/- 8.2). Similar results were obtained by intraperitoneal administration, but in this case, mice showed a marked decrease of body weight. When IL-1 beta was administered in combination with nHuTNF-alpha, pulmonary metastatic tumors decreased much more than when IL-1 beta was administered alone. When the control group had 18.6 +/- 12.7 metastatic tumors, the nHuTNF-alpha group had 12.3 +/- 3.9 and the IL-1 beta group had 12.8 +/- 8.0, the group which was administered both cytokines had a significantly decreased number of 5.6 +/- 3.3 metastatic tumors. This antiproliferative effect of IL-1 beta in combination with nHuTNF-alpha was reduced by the intravenous administration of anti-asialo GM1 antibody and carrageenan. The number of metastatic tumors was increased from 8.9 +/- 8.0 to 18.8 +/- 11.4 by anti-asialo GM1 antibody and from 9.5 +/- 6.8 to 28.0 +/- 12.3 by carrageenan. It was suggested that asialo GM1-positive cells and macrophage were two of the most important effectors of the antiproliferative effect of IL-1 beta and TNF-alpha.
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PMID:Antitumor effect of recombinant human interleukin-1 beta alone and in combination with natural human tumor necrosis factor-alpha. 212 75

The myelopoietic stimulation which occurs in mice bearing metastatic Lewis lung carcinoma (LLC-C3) tumors is accompanied by immune suppression and the appearance of myelopoiesis-associated immune suppressor cells in the bone marrow and spleen. Low doses of recombinant murine interferon-gamma (IFN-gamma) plus recombinant human tumor necrosis factor-alpha (TNF-alpha) were used to limit myelopoiesis and, in turn, reduce the presence of myelopoiesis-associated immune suppressor cells in LLC-C3 tumor bearers. Neither IFN-gamma nor TNF-alpha alone had any effect in vitro on the growth of myeloid progenitor cells into colonies or on the suppressive activity of bone-marrow cells from LLC-C3-bearing mice. However, the combination of low doses of IFN-gamma and TNF-alpha synergistically inhibited both the growth of myeloid progenitor cells into colonies and the suppressive activity of bone-marrow cells from tumor-bearers. Similar results were obtained in vivo. When used alone, neither IFN-gamma nor TNF-alpha had any effect on myelopoiesis or on suppressor-cell activity. When combined, IFN-gamma plus TNF-alpha synergistically suppressed myelopoiesis and the presence of immune suppressive cells both in the bone marrow and in the spleen of tumor bearers. T-lymphocyte blastogenic and NK cytotoxic activities of the tumor-bearers were restored only after treatment with both IFN-gamma and TNF-alpha.
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PMID:Myelopoiesis-associated suppressor-cell activity in mice with Lewis lung carcinoma tumors: interferon-gamma plus tumor necrosis factor-alpha synergistically reduce suppressor cell activity. 214 98


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