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

Cultured murine bone marrow-derived macrophage (BMM phi) can be induced to secrete tumoricidal activity in vitro when activated with recombinant IFN-gamma and bacterial lipopolysaccharide (LPS). We have analyzed this activity for tumor specificity, relationship to tumor necrosis factor-alpha (TNF-alpha), serine proteases, and reactive nitrogen intermediates, and partially purified this activity by high pressure liquid chromatography. Cytolytic activity was recovered in conditioned culture supernatants of serum-free cultivated BMM phi treated with a combination of IFN-gamma and LPS but was not inducible by either stimulant alone. It selectively affected tumor cells of murine as well as human origin irrespective of sensitivity towards recombinant murine TNF-alpha (r-muTNF-alpha), but did not significantly affect non-tumorigenic cells of either species. It was inactivated by 56 degrees C, trypsin, and neuraminidase treatment, but could not be inhibited by neutralizing antibodies against r-muTNF-alpha or serine protease inhibitors. Tumoricidal activity was purified approximately 10-fold by gel filtration and eluted as a major peak with a Mr of 170 kDa, containing a single predominant protein band of approximately 170 kDa on SDS-PAGE analysis, which is shown to be a disulfide linked glycoprotein heterodimer of 110 and 58 kDa subunits (gp170). Expression of this glycoprotein was strongly dependent on activation of BMM phi by a combination of IFN-gamma and LPS but was only marginally induced by either stimulant alone. Furthermore, the level of gp170 expression was quantitatively correlated with the tumoricidal activity of BMM phi culture supernatants, whereas no such correlation was found with respect to the amount of secreted TNF-alpha or reactive nitrogen intermediates. These data demonstrate that activated murine BMM phi secrete a tumoricidal activity, which is not related to TNF-alpha, serine proteases, or reactive nitrogen intermediates, but is closely associated with a 170 kDa glycoprotein composed of two subunits with Mr's of 110 and 58 kDa.
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PMID:Characterization and partial purification of a high molecular weight tumoricidal activity secreted by murine bone marrow macrophages. 162 98

It has been reported that the assembly of MHC class I molecules in mutagenized cell lines could be induced by specific binding peptides. We have now demonstrated that the defect in assembly between heavy and light chains of class I molecules naturally occurred in tumor cells of one spontaneous ovarian carcinoma detected by one-dimensional isoelectric focusing of immunoprecipitates with anti-monomorphic class I MAb (W6/32) and by immunostaining with free heavy chain and beta 2m-specific MAbs. In vitro treatment of the tumor cells with IFN-gamma induced the assembly and surface expression of majority class I molecules (A2.1, B7, B15, Cw6, Cw7 out of A2.1, A2*, B7, B15, Cw6, Cw7). Moreover, assembly of A2 and Cw6 was induced by exposure of the tumor cells to a HLA A2-binding peptide K62 derived from influenza A matrix protein. Autologous blood T lymphocytes were activated in mixed lymphocyte-tumor cell culture (MLTC) by the IFN-gamma-treated but not by the unmanipulated tumor cells. Although activated lymphocytes damaged both IFN-gamma-treated and untreated tumor cells, the alpha class I MAb (W6/32) efficiently inhibited the lysis of IFN-gamma-treated targets, but not the untreated targets. These results indicate that the defect of MHC class I assembly may result in the escape of tumor cells from immune response.
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PMID:Assembly of MHC class I molecules in ex vivo carcinoma cells induced by IFN-gamma or by a binding peptide. 162 53

It is well documented that activated macrophages, but not nonactivated ones, kill tumor cells in vitro without damaging normal cells. We, however, have previously shown that embryo-derived teratocarcinoma cells (F9, P19, PCC4) are efficiently killed by nonactivated macrophages as well as by activated ones. Whereas other tumor cells are killed extracellularly by macrophages, we found that F9 teratocarcinoma cells are phagocytosed alive by macrophages and subsequently killed intracellularly by a process dependent on intact lysosomal function. Neither the H-2 antigens nor the mRNAs for the alpha-chain and beta 2-microglobulin are detectable in embryo-derived teratocarcinoma cells. An obvious explanation for this unique killing is that the nonactivated macrophages recognize and kill these cells due to their lack of class I MHC antigen expression, assuming that class I MHC gene products on the target cells switch off the cytolytic machinery of nonactivated macrophages. Our present findings demonstrate that there is no correlation between H-2 antigen expression on tumor cells and their susceptibility to killing by macrophages. Retinoic acid-differentiated F9 cells and P19 cells expressing H-2 antigen after exposure to MAF (IFN-gamma) were sensitive to the killing by nonactivated macrophages. Hybrids that arose from fusion of P19 teratocarcinoma cells with embryonal normal fibroblasts (C57BL/6), which displayed the morphology of embryonal carcinoma stem cells and expressed H-2 antigens, were also sensitive to the killing by nonactivated macrophages. On the other hand, the H-2-negative testicular 402AX teratocarcinoma cells and K1735P melanoma cells were both resistant to the killing by nonactivated macrophages. We concluded that the unique killing of embryo-derived teratocarcinoma cells by nonactivated murine macrophages is not related to a lack of H-2 antigen expression.
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PMID:The unique killing of embryo-derived teratocarcinoma cells by nonactivated murine macrophages is not due to a lack of H-2 antigen expression. 162 57

The molecular events during the anti-tumor response induced by interleukin (IL)-4 were investigated by quantitative polymerase chain reaction. The growth of Chinese hamster ovary cells transfected to produce IL-4 (CHO.T1) was strongly suppressed when cells were injected intraperitoneally into nude mice and this suppression was accompanied by the rapid accumulation of activated macrophages. Peritoneal cells from such mice were analyzed for mRNA induced by IL-4. Correlating with a high local IL-4 concentration, several transcripts were found to be up-regulated during the early phase of the anti-tumor response [IL-4 receptor, IL-5, tumor necrosis factor (TNF) and interferon (IFN)-gamma]. The functional relevance of the elevated mRNA levels was analyzed by injection of CHO.T1 cells together with anti-cytokine monoclonal antibodies (mAb). In contrast to anti-IL-5 and anti-TNF mAb, an anti-IFN-gamma mAb interfered with the anti-tumor response demonstrating the involvement of IFN-gamma during the IL-4-induced tumor suppression. Tumor growth in anti-IFN-gamma mAb-treated animals was significantly delayed in comparison to anti-IL-4 mAb-treated mice, suggesting that IFN-gamma-independent effector cells may also be involved.
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PMID:Interleukin-4-mediated tumor suppression in nude mice involves interferon-gamma. 162 21

After retrovirus-mediated interferon (IFN)-gamma gene transfer, tumor cells constitutively produce IFN-gamma and subsequently increase their surface expression of class I major histocompatibility complex antigens. Such cells are useful for evaluating the comprehensive anti-tumor activity of IFN-gamma in vivo in the mouse. When implanted, the IFN-gamma-producing tumor cells usually lose their tumorigenicity due to specific and/or nonspecific immune responses against the tumor which are probably augmented by the tumor-derived IFN-gamma. This specific immunity is mediated by CD8+ effector cells, i.e. cytotoxic T lymphocytes. Other in vivo effects due to IFN-gamma gene transfer vary with different types of tumor. These results imply a promising potential of tumor-cell targeted IFN-gamma gene therapy against cancer.
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PMID:Transfection of interferon-gamma gene in animal tumors--a model for local cytokine production and tumor immunity. 164 93

Treatment of human colorectal tumor cells (LS174T, HT-29, and WiDr) with analogues of cyclic AMP (cAMP) (dibutyryl-cAMP and 8-Cl-cAMP) selectively enhances the expression of carcinoembryonic antigen (CEA). Dose and temporal kinetics results revealed that 8-Cl-cAMP was approximately 100-fold more potent than dibutyryl-cAMP for increasing CEA expression. Results demonstrated that 8-Cl-cAMP treatment of LS174T quantitatively increased CEA levels in cell extracts 2-fold, increased anti-CEA monoclonal antibody (MAb) binding to the tumor cell surface, and induced the appearance of CEA-related mRNA transcripts. The findings suggest that 8-Cl-cAMP is capable of regulating CEA expression at transcriptional and/or post-transcriptional levels. Other human tumor cells, as well as normal cell types which do not constitutively express CEA, remained CEA-negative following 8-Cl-cAMP treatment. Moreover, the level of expression of other human tumor antigens as well as antigens of the major histocompatibility complex were not changed by 8-Cl-cAMP treatment, suggesting some selectivity for CEA regulation by this cAMP analogue. In vivo administration of 8-Cl-cAMP to athymic mice bearing LS174T tumor xenografts increased the amount of anti-CEA MAb bound to tumor extracts as well as the tumor localization of a radionuclide-conjugated anti-CEA MAb. The results indicate that 8-Cl-cAMP can selectively upregulate CEA expression on human colorectal tumor cells in vitro and in vivo. Interestingly, IFN-gamma treatment of the LS174T cells fails to enhance or induce expression of CEA or any of the histocompatibility leukocyte antigens. Thus, 8-Cl-cAMP treatment regulates CEA expression through another cellular pathway which may involve cAMP-dependent protein kinase.
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PMID:Carcinoembryonic antigen regulation in human colorectal tumor cells by a site-selective cyclic AMP analogue: a comparison with interferon-gamma. 164

Leukoregulin is a naturally occurring immunologic cytokine which increases membrane permeability and drug uptake in tumor cells but not in normal cells. In this paper we show that leukoregulin also increases membrane permeability of Herpes simplex virus type 1 (HSV-1)-infected cells. More importantly, we demonstrate that leukoregulin significantly enhances the ability of acyclovir (acycloguanosine, ACV) to inhibit the cellular release of infectious HSV-1. The ability of 1-100 microM ACV to inhibit infectious HSV-1 production is increased up to 100-fold when HSV-1-infected human amnion (WISH) cells are treated with 5 units leukoregulin/ml and ACV 3 hr after virus infection. Under these conditions, leukoregulin alone is unable to inhibit HSV-1 infectivity. In addition, three unrelated cytokines, interleukin-1 alpha (IL-1), interferon (IFN)-alpha and IFN-gamma lack the ability to enhance the anti-HSV actions of ACV when their treatment is initiated after HSV-1 infection. These findings demonstrate that a combination of immunotherapy and chemotherapy can produce a substantial inhibition of herpesvirus replication and provide a rationale for the application of this approach to the interventive treatment of virus infection.
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PMID:Leukoregulin, a novel cytokine enhances the anti-herpesvirus actions of acyclovir. 164 27

Tumor-infiltrating lymphocytes (TIL) were obtained from a biopsy of a patient with a Ki-1-positive large cell lymphoma of the skin. Immunohistologic studies of the large anaplastic tumor cells showed an "aberrant" T "helper/inducer" phenotype (CD30 + CD3-CD4+ CD8-IL-2R + HLA-DR+). Using cDNA probe for the constant region of the T-cell receptor (TCR) beta gene, the cells were identified by their distinct monoclonal rearrangement of T-cell receptor (TCR)-beta DNA. Tumor cells isolated from biopsies were cultured in the presence of interleukin-2 (IL-2). Outgrowing lymphocytes were cloned, expanded in vitro, and 11 clones were subjected to phenotypic analysis: ten clones showed a predominantly CD4-positive T "helper/inducer" phenotype whereas one clone expressed CD8 T "cytotoxic/suppressor" antigens. In contrast to the tumor cells, cells of all clones grown in vitro expressed the TCR-associated CD3 complex. Furthermore, cells from all clones analyzed expressed CD5, CD7, CD45RO (UCHL1), CD11a (LFA-1), CD25, and HLA-DR antigens. Cells of two of ten CD4-positive clones expressed CD45RA (2H4) in addition to UCHL1. T-cell clones isolated from the tumor and grown in vitro exhibited individual DNA restriction band patterns different from that of a DNA tumor biopsy specimen. Therefore, the authors conclude that these T-cell clones represent presumably nonmalignant TIL. All clones tested secreted interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha in vitro. Nine of 11 clones were found to secrete additionally IL-2 and IL-4 upon stimulation with phytohemagglutinin (PHA) whereas two clones did not secrete detectable amounts of IL-4. Selective growth of TIL in the presence of IL-2 opens the possibility to use these cells in adoptive immunotherapy of cutaneous T-cell lymphoma (CTCL). Cytokines secreted by TIL cells in vitro (IL-2, IL-4, IFN-gamma, TNF-alpha) may be involved in their antitumorigenic activity. Moreover, these data implicate that CD4-positive TIL derived from CTCL cannot be grouped into different subsets based on the production of IL-2, IL-4, IFN-gamma, and TNF-alpha.
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PMID:Tumor-infiltrating lymphocytes isolated from a Ki-1-positive large cell lymphoma of the skin. Phenotypic characterization and analysis of cytokine secretion. 165 3

Pretreatment of the human melanoma cell line, A375, and the human colon carcinoma cell line, HT-29, with certain cytokines was found to increase the vulnerability of these cells to monocyte-mediated killing. This activity was found to correlate with increased expression of intercellular adhesion molecule-1 (ICAM-1) on the tumor cells and was blocked by anti-ICAM-1 antibodies. Both IFN-gamma and TNF induced large increases in the ICAM-1 expression on both cell lines and increased the susceptibility of the tumor cells to monocyte-mediated killing. IFN-alpha and IL-1 beta, however, induced only small increases in ICAM-1 expression and enhanced the lysis of the A375 cells but not the HT-29 cells by monocytes. These differences may be the result of a higher basal expression of ICAM-1 found on the A375 cells when compared with the HT-29 cells. These data indicate that regulation of ICAM-1 expression on tumor cells can alter the vulnerability of these cells to lysis by monocytes.
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PMID:Cytokine-induced enhancement of ICAM-1 expression results in increased vulnerability of tumor cells to monocyte-mediated lysis. 167 88

Major histocompatibility complex (MHC) antigens and intercellular adhesion molecule-1 (ICAM-1) play important roles in immune response. In order to investigate the association between renal cell cancer (RCC) and host's immune system, expression of MHC antigens and ICAM-1 was examined on RCC. Immunohistochemical analysis revealed a positive correlation between the expression of MHC antigens and ICAM-1. In general, tumor with higher degree of mononuclear cell infiltration expressed MHC antigens and ICAM-1 more frequently and intensely. Among cytokines which were reported to be potent inducers of ICAM-1 on malignant melanoma cell lines, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha augmented the expression of ICAM-1 on ACHN cells whereas ICAM-1 and class I antigens on KRC/Y cells. IFN-alpha enhanced MHC class I antigens but not ICAM-1. Class II antigen expression of both cell lines was augmented by only IFN-gamma. These results suggest that cytokines which could be produced by tumor-infiltrating mononuclear cells, especially IFN-gamma and TNF-alpha, might modulate expression of MHC antigens and ICAM-1, and influence host immune response against RCC.
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PMID:[Expression of major histocompatibility complex antigens and intercellular adhesion molecule-1 (ICAM-1) on renal cell cancer. De novo expression and modulation by cytokines on renal cell cancer cell lines]. 167 73


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