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

Treatment of H-2-deficient nonmetastatic B16 melanoma cells with physiological doses of interferon gamma (IFN-gamma) reduced cellular growth in vitro but induced a shift to the lung-colonizing phenotype as assessed after intravenous injection of the treated cells. As little as 1 antiviral unit of recombinant IFN-gamma per ml induced B16 cells to form 3-40 pulmonary metastases in each injected mouse, whereas a 1000-fold higher concentration of IFN-beta was required to see similar effects. IFN-gamma may induce cell-surface molecules that contribute to the metastatic ability of the tumor cells. The efficient enhancement of metastatic ability after IFN-gamma treatment of the B16 cells was paralleled by an increased H-2 antigen expression and decreased sensitivity to natural killer cells. The experiments support the idea that metastasis may not depend exclusively on stable genetic changes or heterogeneity within a tumor population but may be also influenced through the modulation of the phenotype by physiological or pharmacological agents. The results are also discussed with regard to the role of different effector cells in tumor cell clearance and in relation to lymphokine-based strategies for therapy.
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PMID:Interferon gamma induces lung colonization by intravenously inoculated B16 melanoma cells in parallel with enhanced expression of class I major histocompatibility complex antigens. 310 68

Large granular lymphocytes (LGL) were obtained by Percoll density gradient centrifugation of peripheral mononuclear cells from 15 patients with hematological malignancies (10 acute leukemias and 5 non-Hodgkin's lymphomas). Five-hour 51Cr-release cytotoxic assay by LGL was performed against frozen autologous tumor cells in these patients. Mean percentage cytotoxicity by LGL was 5.6%, and this was enhanced to 15.0% by the addition of IFN-beta to the culture medium. A decrease of cytotoxicity was observed when LGL was treated with anti-Leu 11b antibody plus complement, or when LGL was pretreated with the unlabelled K562 as a competitive inhibition assay. The addition of monocytes also induced a decrease of cytotoxicity, suggesting that monocytes may act as a suppressive agent in autologous tumor cell killing by LGL.
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PMID:[Lymphocyte cytotoxicity against autologous tumor cells and the effect of interferon-beta on their activities. (2) Evaluation of large granular lymphocytes (LGL)]. 310 77

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

A brief exposure (for 6 h) of U937 cells to interferon (IFN)-gamma (500 U/ml) followed by a long term incubation of cells in normal medium for 8 or more weeks resulted in the induction of cells that were refractory to the anticellular and differentiating effects of not only IFN-gamma but also IFN-alpha and IFN-beta at concentrations up to 10(4) U/ml. In addition, the cells became insensitive to the potent differentiating effect of the phorbol ester--tumor promoting agent (TPA). However, the resistant cells retained their sensitivity to the antiviral effect of different IFNs and were fullu responsive to the induction of endonuclease 2',5'-oligoadenylate (2-5A) synthetase by IFN. Furthermore, the resistant cell population appeared to be homogeneous because clones derived from single cells from this population all exhibited the same resistant phenotype to IFN and TPA. These results suggest that induction of resistant U937 cells may involve a dedifferentiation process which results in the formation of an immature cell population that do not respond to the differentiating and/or anticellular effects of various types of IFNs.
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PMID:Biological characteristics of interferon-r-induced resistant histiocytic lymphoma cell line U937. 311 22

Human peripheral blood monocytes and NK cell enriched lymphocytes were purified by counterflow centrifugal elutriation. The cell populations were characterized by surface marker analysis using monoclonal antibodies. A variety of molecules were found to be capable of activating monocytes and NK cells to enhanced tumoricidal activity. Tumoricidal activity was evaluated using a colorimetric microassay. Numbers of tumor cell targets surviving exposure to monocytes or NK cells were calculated by computer analysis of colorimetric data derived by target cell-dependent dye reduction. The results indicated that monocyte effector cells were cytotoxic to the NK sensitive K562 cell line and to the monocyte sensitive TU5 line. Depletion of NK contaminants from the monocyte population by complement mediated cytolysis did not affect the capacity of the monocytes to kill either target. Monocyte mediated cytotoxicity was enhanced by treatment of the monocytes with recombinant IFN-alpha, IFN-beta, or IFN-tau; each in a dose-dependent manner. Simultaneous treatment of monocytes with IFN-alpha and IFN-tau resulted in additive but not synergistic effects. NK cell cytotoxicity was enhanced by treatment with IL-2 or IFN-tau. Enhancement of monocyte and NK cell cytotoxicity by IFN or IL-2 was dependent upon the time in culture of the effector cells, the duration of the effector phase, and the effector to target cell ratio. IFN or IL-2 treatment alone did not reduce target cell viability. The results suggest that monocytes as well as NK cells are capable of providing a natural defence against neoplasia, that monocytes can kill NK targets and NK cells can kill monocyte targets, and that these cytotoxic activities are enhanced by IFN or IL-2.
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PMID:Recombinant interferons or interleukin-2 increase cytotoxicity by human monocytes and NK cells. 311 69

In tumor cell lines in which oncogene expression is abnormal, modulation of the expression of the oncogene (myc, src, or ras) by interferons (IFNs) has been observed concurrently with cell growth inhibition or phenotypic reversion. Oncogene expression has also been reported to vary during the differentiation of several neoplastic cell lines. Treatment of monolayer cultures of A431, a human epidermoid carcinoma cell line, with IFN-gamma resulted in rapid morphological alterations and cell death not seen with either IFN-alpha or IFN-beta. These changes were accompanied by elevated expression of mRNA's for p21 (the c-ras gene product) and the epidermal growth factor receptor as well as increases in the biosynthetic rate of their respective proteins. These effects likewise appeared to be specific for IFN-gamma. Growth inhibition by IFN-gamma was also observed when A431 cells were grown in a three dimensional in vitro culture system. Immunohistochemical staining of these "tumoroids" with a differentiation specific, anti-keratin antibody indicated that IFN-gamma enhanced expression of this keratin. This observation suggests that the killing by IFN-gamma of A431 cells may result from an acceleration of terminal differentiation.
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PMID:Interferon-gamma induces altered oncogene expression and terminal differentiation in A431 cells. 312 20

We investigated the effects of human interferon(IFN)-beta and -gamma on protein kinase C activity in human HEp-2 and KHm-14 tumor cells during IFN-induced inhibition of cell growth. Cytosolic protein kinase C activity in both cell lines was strikingly decreased following treatment with either IFN-beta or -gamma. In the particulate fraction, IFN-gamma decreased protein kinase C activity within 1 hr but it reappeared after 24 hr, whereas IFN-beta decreased the activity during the inhibition of cell growth. Furthermore, phorbol-12,13-dibutyrate(PDBu)-binding activity was altered in parallel with the changes in protein kinase C activity induced by the IFNs. In summary, we showed that IFN-beta and -gamma cause long-term modulation of protein kinase C activity in these cultured tumor cells.
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PMID:Modulation of protein kinase C activity during inhibition of tumor cell growth by IFN-beta and -gamma. 312 51

Despite quantitative as well as qualitative differences, all three types of IFN (IFN-alpha, IFN-beta, and IFN-gamma) modulate the synthesis as well as the expression of class I and class II histocompatibility Ag and a melanoma-associated Ag located in the plasma membrane as well as the cytoplasm of human melanoma cells. By employing inhibitors of RNA and protein synthesis it was demonstrated that IFN-alpha and -beta increase the expression of histocompatibility products and this tumor-associated Ag by a process not requiring new protein synthesis. In contrast, IFN-gamma does require de novo protein synthesis for its modulatory activity. Thus, it appears that IFN might trigger various adaptive functions in different cell lineages by inducing at least two separate sets of responses specific for either IFN-alpha and -beta or IFN-gamma. Because the induction requirements for (2'-5')-oligoadenylate synthetase as well as for the development of a cellular antiviral state by different IFN also display a similar protein synthesis dependence pattern, the present results suggest that a similar set of cellular mediators may be involved in the modulation of antigenic expression by IFN-gamma in human melanoma cells.
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PMID:Recombinant human IFN-gamma, but not IFN-alpha or IFN-beta, enhances MHC- and non-MHC-encoded glycoproteins by a protein synthesis-dependent mechanism. 312 9

Low density fractions of Percoll density gradient centrifugation of peripheral mononuclear cells contained the majority of large granular lymphocytes (LGL). LGL were used for 5-hr 51Cr release cytotoxic assay against autologous tumor cells in 20 patients with hematological malignancies (9AML, 4ALL and 7NHL). Mean % cytotoxicity (% CTX) was 6.0%, and the addition of IFN-beta and IL-2 in the medium induced the significant increase of % CTX to 15.0% and 26.1%, respectively. When LGL cultured in medium containing IFN-beta and IL-2 were assessed for cytotoxicity daily for 8 days, the enhancement of % CTX by IFN-beta was declined in a few days, while the enhancement by IL-2 was sustained for more than 8 days. The pretreatment of LGL with anti Leu-11 (CD16) plus complement abrogated the enhancing effect by IFN-beta or IL-2, but not with anti Leu-1 (CD5) plus complement. When this treatment was done on day 8 of IL-2 cocultivation, anti Leu-11 plus complement suppressed cytotoxicity significantly, and anti Leu-1 plus complement also induced mild suppression. The phenotypic characteristics of cells revealed the significant increase of anti Leu-19+ cells in IL-2 stimulated day 8 cells. High density fractions of Percoll gradient contained mostly T lymphocytes and showed no cytotoxicity against autologous tumor cells. However, cocultivation with IL-2 for 8 days induced the cytotoxicity, associated with increased number of anti Leu-19+ cells. These results suggested that IL-2 induced cytotoxic activity against autologous tumor cells might be related to the increase of anti Leu-19+ cells.
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PMID:[The effect of IL-2 and IFN-beta on autologous tumor cell kill by Percoll separated LGL fractions]. 315 15

To address the mechanisms that regulate expression of specific growth-related nuclear proto-oncogenes, the transcript levels of the c-fos, c-myc, (2'5')-oligoadenylate synthetase, IFN-alpha 1, and IFN-beta 1 genes have been measured in the human leukemic cell lines KG-1, U937, and HL-60 following growth stimulation by serum, induction of differentiation by tumor-promoting agents, and/or treatment of cells with exogenously supplied alpha interferon (rIFN-alpha 2). Production of fos and myc RNA was measured by S1 mapping, using fos DNA probes which identified either primary unspliced transcripts or steady-state-spliced mRNA levels, and using a myc probe which spanned the two major c-myc start sites, P1 and P2. Pretreatment of a quiescent KG-1 cell population with IFN for 18 hours before serum addition decreased the stimulation of both fos and myc RNA production. In HL-60 and U937 cells, IFN pretreatment had no inhibitory effect on serum-induced fos or myc transcription; however, in U937, rIFN-alpha 2 treatment alone stimulated fos mRNA 11-fold. Expression of 2'5'oligoadenylate synthetase was induced in IFN-treated cultures but not in cells stimulated with serum alone. No serum-induced IFN-alpha 1 or IFN-beta 1 gene expression was observed in KG-1 or U937 cells. These results demonstrate that exogenous rIFN-alpha 2 treatment of quiescent KG-1 cells can antagonize the effect of growth factors by altering expression of nuclear proto-oncogenes, but in general growth inhibition is not obligatorily coupled to inhibition of proto-oncogene transcription.
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PMID:Modulation of nuclear proto-oncogene expression and cellular growth in myeloid leukemic cells by human interferon alpha. 316 96


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