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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiviral action of recombinant human tumor necrosis factor (TNF) was studied using assay systems to determine inhibition of viral cytopathic effect (CPE), as well as suppression of virus growth measured by plaque assays. TNF was cloned and prepared by Asahi Chemical Industry, Japan. Antiviral activity against human herpes simplex virus (HSV) types 1 and 2, cytomegalovirus (CMV), varicella-zoster virus (VZ), vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMC), was demonstrated in human diploid fibroblasts following pretreatment with TNF overnight. The antiviral action was completely neutralized by anti-interferon (IFN)-beta serum, but not by anti-IFN-alpha or -gamma antibodies. This suggested the induction of IFN-beta by TNF. The antiviral action was synergistically enhanced by human IFN-gamma. Several non-human cell lines were tested but 10 of 11 failed to be protected from VSV- and/or EMC-induced CPE following pretreatment by TNF. The anticellular effects of TNF were tested in human and in non-human tumor cell lines. The results indicate that the susceptibility of cells to the two activities of TNF, antiviral and anticellular, was distinct, and that antiviral activity of TNF is more species-specific than its anticellular action.
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PMID:Antiviral effects of recombinant human tumor necrosis factor. 244 53

Macrophage colony-stimulating factor (M-CSF) was investigated as a stimulator of ADCC to the murine R1.1 thymoma target by murine peritoneal exudate macrophages which were elicited by proteose peptone. Both an 125IUdR release and a viable cell count assay were used. The latter assay avoids radiation damage, and the fate of the targets can be determined over a long period. Pretreatment of macrophages for several days in culture with lymphokine (LK) from concanavalin A-induced mouse spleen cells moderately stimulated ADCC. Preincubation of macrophages with conventional or recombinant human M-CSF or immunoaffinity-purified mouse M-CSF alone had little effect. However, M-CSF greatly enhanced ADCC to the tumor target when used as a costimulant with LK, IFN-gamma, IFN-alpha, IFN-beta, or IL-2 to pretreat macrophages. Incubation of macrophages with LK or LK plus M-CSF for 2 days generated stronger ADCC than 1- or 3-day incubations. Enhancement of LK-stimulated ADCC by M-CSF appeared to plateau at about 1000 U/ml. The enhancement of macrophage cytotoxicity when stimulated with IFNs or IL-2 was most effective at the lowest active concentration of these LKs. At 1 U/ml IFN-gamma or IL-2, or 5 U/ml IFN-alpha or IFN-beta, M-CSF boosted ADCC activity to that using 10-fold of the LK alone. IL-1, IL-4, and TNF had little or no stimulating activity for ADCC alone or with M-CSF, and the other hemopoietic growth factors IL-3 and GM-CSF did not promote this effector function alone or with IFN-gamma. We previously showed that M-CSF boosted macrophage antibody-independent killing of TU5 sarcoma targets with or without LK (Cell. Immunol. 105, 270, 1987). These studies thus show that M-CSF is a positive regulator of both macrophage-nonspecific tumor lysis and ADCC.
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PMID:Stimulation of macrophage antibody-dependent killing of tumor targets by recombinant lymphokine factors and M-CSF. 246 Feb 49

Alveolar II pulmonary tumor cells (A549), maintained in continuous tridimensional organotypic culture, were used in an attempt to investigate whether there could be a relationship of the 2',5'-oligoadenylate (2,5A) synthetase pathway to the antiproliferative activity of interferons (IFNs) in this particular tumor cell model. IFN-alpha 2, -beta and -gamma were used separately and in combinations. IFN-alpha 2 and -gamma demonstrated an inhibitory effect on the nodule growth, whereas IFN-beta did not. Moreover, combinations of IFN-alpha 2 and -gamma resulted in a significant synergistic antiproliferative activity; IFN-beta only potentiated slightly the effect of IFN-gamma. All three IFNs induced an increase in the 2,5A synthetase activity, indicating a discrepancy with the pattern of anticellular activity. Furthermore, whereas the combination of IFN-alpha 2 and -gamma resulted in a synergistic antiproliferative effect, no synergism was observed in the induction of the enzyme. These results show that there is a lack of correlation between the sensitivity or the resistance to IFNs of A549 tumor nodules and the induction of the 2,5A synthetase activity.
Tumour Biol 1988
PMID:Human lung cancer nodules in organotypic culture: no evidence of correlation between the antiproliferative effects of interferons and the induction of 2',5'-oligoadenylate synthetase. 246 79

Modulation of class I and II MHC antigen expression by interferons has been the focus of considerable attention because the regulation of these molecules serves as a useful model system to study factors exerting transcriptional control of gene expression and because of the relevance of these molecules to expression of the neoplastic phenotype. While our knowledge of the molecular mechanisms regulating the ability of interferon to mediate enhancement of MHC genes has increased, this information is primarily based on studies employing established cell lines, and it remains to be determined whether similar controls are also exerted in short term cultured cell lines. In this short review, we have discussed the structural organization of the 5' flanking regions of the MHC genes, with special emphasis on class II genes, and the implications of these data for the transcriptional regulation of these and of other interferon inducible genes. Present evidence indicates the existence of at least four conserved upstream sequences which are shared by interferon responsive genes and which appear to be involved in the transcriptional control of these genes. The pattern of metabolic requirements for IFN-alpha and IFN-beta versus IFN-gamma upregulation of the class I and II MHC genes suggests that the regulation of gene expression by IFN-gamma requires unique regulatory molecules, i.e. newly synthesized proteins, which are not required by IFN-alpha and IFN-beta treated cells. These putative mediators of gene expression are likely to be shared by many of the biochemical induction pathways involved in the regulation of genes which exhibit interferon responsive sequences. However, in addition to common regulatory signals, other specific pathways and possibly additional regulatory sequences, are also required to account for locus--or subunit-specific patterns of antigenic modulation. Future studies are required, including those employing short term tumor cell cultures, to precisely define the molecular details of gene regulation of class I and II MHC genes, as well as other interferon--responsive--genes, by interferons. These investigations will not only prove valuable on a fundamental scientific level, but they will also be crucial for the more effective application of interferons in clinical oncology.
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PMID:Regulation of class II MHC gene expression by interferons: insights into the mechanism of action of interferon (review). 246 33

Freshly isolated cells from patients with pleural or peritoneal effusions cytologically diagnosed as adenocarcinoma (n = 43), malignant nonepithelial neoplasms (n = 10), and benign (n = 8) were analyzed for expression of constitutive levels of the tumor antigens TAG-72 [recognized by monoclonal antibody (MAb) B72.3] and carcinoembryonic antigen (CEA) (recognized by MAb COL-4) as well as the class I and class II major histocompatibility (MHC) antigens, and the ability of human interferons (Hu-IFNs) to enhance cell surface expression of those antigens as measured by MAb binding. Both type I and type II IFNs enhanced the expression of TAG-72 and CEA and altered the level of expression of the MHC antigens. Comparative studies of three different Hu-IFNs (IFN-alpha A, IFN-beta ser, and IFN-gamma) revealed that IFN-gamma was the most potent in augmenting either B72.3 or COL-4 binding. Unlike the IFN-gamma -mediated induction of the class II human leukocyte antigens, the change in tumor antigen expression consisted of enhanced constitutive antigen expression; de novo induction of either TAG-72 or CEA could not be achieved by either type I or type II IFN. Of 43 effusions isolated from different adenocarcinoma patients, 42 (97.7%) expressed either CEA or TAG-72, and treatment with Hu-IFN increased the level of expression of either antigen in 36 of 42 samples (85.7%). These studies demonstrate the augmentation of tumor-associated antigens on human carcinoma cells isolated from serous effusions by Hu-IFNs which may be used to enhance the targeting of conjugated MAbs to human carcinoma lesions.
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PMID:Selective interferon-induced enhancement of tumor-associated antigens on a spectrum of freshly isolated human adenocarcinoma cells. 246 27

The acute phase cytokines: interleukin 1, tumor necrosis factor alpha (cachectin) and beta (lymphotoxin), hepatocyte stimulating factor and several interferons, all belong to the family of endotoxin-inducible, low molecular weight proteins. Their synthesis in macrophages, fibroblasts, lymphocytes, epithelial and some tumor cells is enhanced by the same cytokines, often in the autocrine manner, and suppressed by dexamethasone. The principal hepatocyte stimulating factor (HSF) regulating synthesis of acute phase proteins is probably identical with IFN-beta 2/BSF-2/IL-6, but other inflammatory cytokines (IL-1, TNF alpha, IFN-gamma) are able to induce distinct sets of acute phase proteins, or to modulate the final response pattern. The effect of hrIFN-gamma on production of acute phase proteins by human hepatoma Hep G2 cells is discussed in detail. It is concluded that the cascades of inflammatory cytokines in different tissues represent amplification and regulatory pathways controlling the development of acute phase response in vivo.
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PMID:The cascade of inflammatory cytokines regulating synthesis of acute phase proteins. 248 65

Lymphokine-activated killer (LAK) cells are cytotoxic for a variety of autologous and allogeneic tumor cells as well as modified autologous cells. It is assumed that LAK cells lyse their targets solely by direct cell to cell contact, possibly involving the degranulation and exocytosis of pore-forming elements, similar to that observed with cytotoxic T lymphocytes and NK cells. Reported here are studies demonstrating that LAK cells release factor(s) that are cytotoxic for a human breast carcinoma cell line, MCF-7, when stimulated with tumor cells. The factor(s) are slow acting and maximum cytotoxicity is observed only in a 72-h cytotoxic assay. The ability of LAK cells to secrete cytotoxic factor(s) is dependent on both the ratio of LAK cells to stimulating tumor cells as well as the length of their coincubation. A number of similarly slow acting cytokines that are cytostatic and/or cytotoxic for tumor cells have been described. We tested the ability of specific polyclonal antibodies directed against TNF, IFN-alpha, IFN-beta, and IFN-gamma to neutralize the cytotoxic supernatant activity. Only antibodies specific for IFN-gamma and TNF were neutralizing. We measured the amounts of IFN-gamma and TNF in the cytotoxic supernatants and determined that increased amounts of IFN-gamma and TNF were released after LAK cell-tumor cell interactions compared to supernatants of LAK cells alone or tumor cell alone. Comparable concentrations of human rIFN-gamma and rTNF resulted in similar levels (50 to 90%) of MCF-7 cell cytotoxicity as those observed with the stimulated LAK cell supernatants. We thus concluded that the majority of the cytotoxic activity released by LAK cells when stimulated with tumor cells was attributed to the synergistic activities of IFN-gamma and TNF. The significance of these observations in relation to the possible mechanisms by which LAK cells mediate cytolysis is discussed.
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PMID:Tumor targets stimulate IL-2 activated killer cells to produce interferon-gamma and tumor necrosis factor. 249 6

Recombinant human interferon beta (rIFN-beta) inhibited in a time- and dose-dependent manner the proliferation of 18/18 human colon carcinoma cell lines in monolayer culture and 8/9 lines in a soft agar assay but had no effect on 4 human fibroblast cell lines. Maximal inhibition of cell proliferation by rIFN-beta required repetitive treatment (every 2 days) with lymphokine (50 units/ml). Furthermore, the inhibitory activity of rIFN-beta was neutralized by polyclonal antibodies against natural IFN-beta. In contrast to rIFN-beta, rIFN-alpha was inactive against all colon cell lines tested, and rIFN-gamma, with the exception of HT-29 cells, was similarly ineffective. These data demonstrate that rIFN-beta is a potent growth inhibitor of colon carcinoma cells in vitro, and suggest that studies on its mechanism of action may lead to a better understanding of the regulation of colon tumor cell proliferation.
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PMID:Growth-inhibitory activity of interferon-beta against human colorectal carcinoma cell lines. 249 20

Reversible transient osmotic blood-brain barrier disruption was used to increase drug delivery to the brain. The authors treated 10 cases of malignant gliomas with intra-arterial chemotherapy after osmotic blood-brain barrier disruption. Ten patients received intra-arterial anticancer drugs (5-FU, ACNU, IFN-beta) after intra-arterial infusion of 20% mannitol to open the blood-brain barrier at the tumor site. Clinical responses in 9 evaluable cases were 1 Complete Response, 3 Partial Responses, 5 No Change and no Progressive Disease in CT examination. Response rate was 44.4% (4/9). The most untoward effect of this method was myelosuppression. Platelet and leukocyte count diminished below 20,000 and 2,000, respectively in 3 cases, and 2 out of these 3 cases died of severe infection. The other complications were eye pain during mannitol infusion in all cases, when the selective catheterization of the internal carotid artery failed to pass the origin of the ophthalmic artery. Decreased activity was seen in 70%, nausea and vomiting in 50%, swelling of external decompression area in 33%, increased neurological deficit in 20%, but all these side effects were transient. This method was considered an effective treatment for malignant gliomas.
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PMID:[Intra-arterial chemotherapy of malignant glioma after osmotic blood-brain barrier disruption]. 250 17

To examine the influence of interferon gamma (IFN-gamma) on tumorigenicity, we established constitutively IFN-gamma-producing cell lines from a malignant mouse neuroblastoma, C1300, by retroviral transfer of a mouse IFN-gamma cDNA. The gene-transferred cells generally showed an enhanced high-level expression of the major histocompatibility complex class I antigens at the cell surface and the transcription levels, irrespective of their IFN-gamma-producing potential. Although in vitro cell growth of these cells was unaffected by the IFN-gamma production, their s.c. tumor growth in syngeneic A/J mice was dependent upon levels of IFN-gamma production; tumors induced by a low-producer line grew well at a rate similar to those induced by the parental one, but tumor growth of a high-producer line was strongly suppressed. This apparent tumor suppression was abolished by simultaneous i.p. injection of anti-Lyt2.2 and/or anti-IFN-gamma monoclonal antibodies, and subsequently large tumors of the high producer were generated. Anti-asialoganglioside GM1 antibodies allowed the high-producer line to induce a substantial but only transient tumor growth, whereas other antibodies, such as anti-Lyt2.1, anti-IFN-beta, and anti-activated macrophage, had no such effect. The mice immunized with the high-producer line were resistant to tumor growth of the parental cells but permitted another kind of A/J tumor line, Sa-1, to induce remarkable tumors. These results indicate that the reduced tumorigenicity of the IFN-gamma high-producer line was due to the augmented specific anti-tumor immunity, in which cytotoxic T lymphocytes seemed to play a decisive role, probably as a result of the immunomodulatory effects of the IFN-gamma derived from the tumor.
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PMID:Exogenous expression of mouse interferon gamma cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity. 251 80


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