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  • 1
    ISSN: 1432-0851
    Keywords: Tumour necrosis factor ; Monocytes ; Gastric cancer ; BCG immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human peripheral blood monocytes cocultured with tumour cells were used as an in vitro model of in situ interactions between tumour-infiltrating macrophages and the tumour. Tumour cells stimulated de novo expression of the human tumour necrosis factor α (TNF) gene in monocytes and caused the release of TNF into the culture supernatant. A group of 14 patients with stage IVA gastric cancer receiving adjuvant chemotherapy (5-FU, Adriamycin, mitomycin C: FAM) or immunochemotherapy (BCG+FAM) was investigated for the ability of monocytes to produce TNF in vitro upon stimulation with tumour cells or purified protein derivative of tuberculin (PPD). Patients were followed at biweekly intervals, i.e. before each instillation of BCG epicutaneously over a period of 10 weeks. It was found that monocytes of some patients receiving BCG at the end of the observation period had an enhanced ability to produce TNF following stimulation with tumour cells. In contrast, such production was not substantially altered during the study period in patients on chemotherapy. PPD-induced TNF production was much weaker and was not significantly changed during this observation time. We infer that BCG immunotherapy may induce the subtle changes in some cancer patients that lead to an increased interaction between monocytes and tumour cells and result in enhanced production of cytokine(s) with antitumour properties.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 104 (1982), S. 307-313 
    ISSN: 1432-1335
    Keywords: Gastric cancer ; Monocytes ; Suppressor cells ; Cytostatic activity ; “Activation”
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The spontaneous nitro-blue tetrazolium (NBT) reduction of monocytes from patients with gastric cancer was assessed and compared with an in vitro monocyte-mediated cytostasis of tumor cell lines and their suppressor activity. The increased NBT reduction correlated with the ability of monocytes to inhibit mitogen-induced normal lymphocyte response and cytostatic activity against L-1210 murine lymphoma cell line. These observations suggest that “activated” monocytes of some cancer patients may play the role of suppressor cells and exert an anti-tumor effect in vitro.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1335
    Keywords: Gastric cancer ; Cellular immunity ; T lymphocytes ; Monocytes ; Follow up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Standard immunological parameters measuring non-specific cellular immune reactivity were determined in 175 patients with different stages of gastric cancer prior to surgery and during follow-up. Several tests measuring monocyte activity were also employed. The total number of T cells and their subpopulations Ta and T29° was unchanged except depression of T29° in stage IV. The blastogenic response of lymphocytes to PHA as assessed by stimulation of protein synthesis was only depressed in stage IV. In contrast the PHA-induced lymphokine production was increased in all patients but the differences were significant for stage III and IV. Monocyte Fc receptor expression was increased in stages II-IV, while nitro blue tetrazolium reduction and antibody dependent cellular cytotoxicity of monocytes was elevated in stage IV. The number of extractable monocytes was not increased. Longitudinal studies suggested that most of the parameters normalized during follow-up. No major long-term impact of chemoimmunotherapy (5-FU+BCG) on the immune parameters was observed except a transient increase in PPD reactivity approximately 1 year after commencement of treatment. In patients with stage III gastric cancer the increased occurrence of suppressor cells (mostly monocytes) and elevated cytostatic activity of monocytes was associated with a longer survival while the increased lymphokine production and Fc receptor expression were seen in the group of patients succumbing earlier. We concluded that most of the changes in immune parameters were seen only in advanced disease and paradoxically disappeared in the course of disease. The determination of monocyte activity seems to be a sensitive indicator of immune system dearrangements in earlier stages of cancer and a useful prognostic factor in gastric cancer.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-2592
    Keywords: Human monocytes ; TNF ; MHC class II ; TNF-receptors ; thalidomide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The control of expression of MHC class II molecules on antigen-presenting cells is important for the induction of immunity, while aberrant expression of these molecules plays a role in the immunopathology of autoimmune diseases. This study explored the role of tumor necrosis factor alpha (TNF) in controlling the level of HLA class II mRNA in human monocytes. Exposure of monocytes to exogenous recombinant TNF (rTNF) selectively up-regulated DRα-mRNA but not DP or DQα-mRNA. Inhibitors of TNF synthesis, pentoxifylline (PTX) and thalidomide, inhibited TNF mRNA accumulation in LPS-activated monocytes and down-regulated DR mRNA but not DP or DQ mRNA. The inhibitory effect of anti-TNF monoclonal antibody (MAb) indicated that endogenously generated TNF acted extracellularly. Anti-p75 TNF-R2 receptor and to a lesser extent anti-p55 TNF-R1 MAbs inhibited TNF-mediated up-regulation of DR mRNA and TNF mRNA. Taken together, this implies that endogenously generated TNF plays a role in controlling isotype-specific MHC class II gene expression in human monocytes/macrophages. These results may have some implications for anti-tumor response and autoimmunity.
    Type of Medium: Electronic Resource
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