UMLS:C0027651 - FACTA Search

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

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

Appropriately activated mononuclear phagocytes mediate contact-dependent tumoricidal activity. Adhesion structures involved in contact-dependent tumor cytotoxicity have not been defined. The present study was aimed at identifying the adhesion structures involved in the tumoricidal activity of activated (IFN-gamma + LPS) human monocytes. Tumor cells of different histological origin were used as targets in a 48-hr cytolysis assay. Anti-CD18 (integrin beta 2 chain) monoclonal antibodies (MAbs) substantially (50-80%) inhibited human monocyte cytotoxicity. When the role of different a-chains was studied, anti-alpha L (CD11a, LFA1), anti-alpha M (CD11b, Mac-1) and anti-alpha X (CD11c, p150,95) caused marginal inhibition, but the effect of the 3 combined was comparable to that of anti-CD18. Anti-CD18 MAb did not affect the release of various cytotoxic molecules (e.g. TNF) by activated human monocytes. Activated monocytes showed augmented binding to target cells and anti-CD18 MAb inhibited the binding of resting and activated monocytes to tumor target cells. While IFN-gamma alone augmented expression of leukocyte integrins and LPS had no effect, the 2 activation signals, combined for optimal stimulation of tumoricidal activity, resulted in no appreciable increase in these leukocyte adhesion molecules, as assessed by flow cytometry. Our results suggest that the augmented CD18-dependent binding of activated monocytes on tumor cells depends mainly upon changes in the adhesive properties of these molecules rather than upon increased numbers on the cell surface. Anti-ICAM-1 MAb significantly reduced monocyte cytotoxicity on tumor cells, which is consistent with a role of the CD11/CD18 adhesion pathway. These results implicate "activated" leukocyte (beta 2) integrins (CD11/CD18) as important adhesion molecules in the contact-dependent tumoricidal activity of human monocytes.
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PMID:Involvement of leukocyte (beta 2) integrins (CD18/CD11) in human monocyte tumoricidal activity. 167 46

ICAM-1-mediated cell-cell adhesion is essential for various immunologic functions, including non-MHC-restricted cytotoxicity. The present study was designed to establish whether shedding of ICAM-1 from melanoma cells occurred and to characterize the effects of soluble ICAM-1 on some cell adhesion-dependent functions. The shed soluble ICAM-1 molecule was detected and quantified by a specific ELISA. Shedding of ICAM-1 could be induced by IFN-gamma and TNF-alpha alone, or more effectively, by a combination of the two cytokines together. The use of purified soluble ICAM-1 enabled us to test for the functional significance of the ICAM-1 shedding from tumor cells. Conjugate formation between the cloned NK cell line CNK6 and the erythromyeloid cell line K562, as well as between lymphokine-activated killer cells and the melanoma cell line M26, could be inhibited by purified soluble ICAM-1 and cell-free supernatants from melanoma cell cultures containing shed ICAM-1. Furthermore, the non-MHC-restricted cytotoxicity mediated by NK and lymphokine-activated killer cells could be abrogated either by purified soluble ICAM-1 or by melanoma cell culture supernatants containing shed ICAM-1. Thus, shedding of ICAM-1 may be one of the mechanisms by which neoplastic cells escape immunosurveillance.
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PMID:Shedding of ICAM-1 from human melanoma cell lines induced by IFN-gamma and tumor necrosis factor-alpha. Functional consequences on cell-mediated cytotoxicity. 168 77

Analysis of lymphokine mRNA expression and protein secretion by about 100 short-term alloreactive T-cell clones revealed marked heterogeneity in the combinations of lymphokines synthesized. This finding argues against a simple model in which T cells express either an unrestricted (Th0) or a restricted (Th1 or Th2) lymphokine profile. Lymphokine titers appeared to be normally distributed, with the percentage of positive clones for any one product determined by the threshold of detection. Accordingly, the observation that CD4+ clones on average produced higher titers of most lymphokines than CD8+ clones indicated that apparent differences between the lymphokine profiles of these two subsets were quantitative rather than qualitative. Patterns of lymphokine gene expression detected in whole tissues or by analysis of single cells and clones were markedly influenced by in vivo priming. Relative levels of expression of IL-4, IFN-gamma and GM-CSF in lymphoid tissues differed in mice undergoing a GvHR or following contact sensitization with OX or immunization with KLH in adjuvant. Consistent with the finding that IL-4 was the major lymphokine mRNA detected in lymph nodes of KLH-primed mice, most short-term KLH-specific clones derived from such mice also expressed IL-4. A similar approach to the detection of lymphokine-secreting T-cell precursors activated late in L. major infection showed that most clones from the L. major-resistant strain, C57BL/6, secreted IFN-gamma without IL-4 whereas most clones from the susceptible strain, BALB/c, secreted IL-4 without IFN-gamma. Differences were also noted in anti-CD3-induced IL-3 production at the single-cell level between CD8+ cells activated in the GvHR or against a tumor allograft. Con A-induced, filler cell-dependent cloning of CD4+ T cells from unprimed mice gave rise both to IFN-gamma-producing and to IL-4-producing clones. A requirement for an undefined, filler cell-dependent signal for development of IL-4-secreting clones was suggested by the finding that clones of normal CD4+ and CD8+ T cells activated in an anti-CD3-induced, filler cell-free system exclusively produced IFN-gamma and IL-3 without detectable IL-4 or IL-6. With a view to developing a single-cell approach to the analysis of lymphokine profiles of in vivo-activated T cells, sensitive assays for IL-3 and other lymphokines were used to measure secreting cells activated in the GvHR or against a tumor allograft.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Heterogeneity in lymphokine profiles of CD4+ and CD8+ T cells and clones activated in vivo and in vitro. 168 85

The immune response at the molecular level is characterized by a carefully coordinated interplay of both cytokine production and receptor induction. The regulation of these molecules including the closely related tumor necrosis factors alpha (TNF) and beta (lymphotoxin, LT) is still incompletely understood. We have examined the effects of various cytokines on the expression of TNF and LT mRNA in human peripheral blood mononuclear cells (PBMC). Northern blot analysis with total cellular RNA from mixed populations of PBMC revealed that genes coding for TNF and LT were not spontaneously expressed. Treatment of PBMC with recombinant interleukin (IL)-2 resulted in a high level expression of TNF and LT mRNA. Whereas IL-1 beta was equally effective as IL-2 in inducing both TNF and LT mRNA, granulocyte-macrophage colony-stimulating factor selectively induced only TNF mRNA. Both TNF and LT mRNA were minimally induced by IL-1 alpha, IL-3, interferon (IFN)-alpha, or IFN-gamma. Similarly TNF alone had little effect on induction of TNF and LT mRNA. In conjunction with IL-2, cytokines such as IFN-alpha, IFN-gamma, or TNF did not interfere with IL-2 induction of TNF and LT mRNA. Interestingly, IL-4 in combination with IL-2 inhibited the IL-2-driven induction of TNF and LT mRNA. This inhibitory effect of IL-4 was also observed at the level of TNF and LT protein secretion. Furthermore, IL-4 was also inhibitory of IL-2-mediated induction of Tac mRNA in PBMC. These results extend the interrelationship of cytokine regulation of TNF and LT expression. In particular, they reveal the previously unrecognized function of IL-4 in antagonizing the IL-2 induction of TNF, LT, and Tac mRNA in PBMC.
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PMID:Cytokine regulation of tumor necrosis factor-alpha and -beta (lymphotoxin)-messenger RNA expression in human peripheral blood mononuclear cells. 169 66

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