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  • 1
    Electronic Resource
    Electronic Resource
    The immunomodulatory effects of urine from patients with superficial bladder cancer receiving intravesical evans BCG therapy (1993)
    Springer
    Cancer immunology immunotherapy 36 (1993), S. 25-30 
    Details
    ISSN: 1432-0851
    Keywords: Bladder cancer ; ICAM-1 ; MHC class II ; BCG therapy ; Interferon γ
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bladder cancer cells were stimulated with urine obtained from patients with superficial bladder cancer who had received treatment using intravesical bacillus Calmette-Guérin (BCG). The urine from the first 12 h following each of six BCG instillations was collected and examined for its biological effect. We evaluated effects that had previously been attributed to cytokines detected in the urine of such patients. The modulation of MHC class II antigen and intercellular adhesion molecule-1 (ICAM-1) expression were studied. Using neutralizing polyclonal antibodies to interferon γ and tumour factor α the relative contribution of these molecules to the effects investigated were determined. When cells were stimulated for up to 48 h with first-instillation urine, little effect was seen in any of the parameters investigated. Urine from the sixth instillation, however, proved to be a potent immunomodulatory agent, inducing MHC class II molecule and ICAM-1 expression. Urine from instillations two to five mediated increasing immunomodulatory effects. When sixth-instillation urine samples were treated with neutralizing antibodies to interferon γ prior to their addition to the bladder cancer cells, a marked and significant decrease in their potency was observed. Only in urine from one patient did any immunomodulatory capability remain after antibody treatment. Neutralizing antibodies to tumour necrosis factor α, however, failed to reduce the ability of any patient's urine to induce ICAM-1 expression. When both antibodies were used simultaneously no further decrease in potency was observed. These studies demonstrate for the first time the potential immunomodulatory and cytotoxic effects of urine produced by patients receiving intravesical BCG. Furthermore, in all samples tested, the major immunomodulatory component was shown to be interferon γ. Although tumour necrosis factor α is produced as a result of BCG therapy, this cytokine did not appear to contribute to the parameters investigated. namely the induction of HLA class II antigens, and cell-surface ICAM-1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01789127
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Production of urinary tumour necrosis factors and soluble tumour necrosis factor receptors in bladder cancer patients afterbacillus Calmette-Guerin immunotherapy (1995)
    Springer
    Cancer immunology immunotherapy 40 (1995), S. 119-124 
    Details
    ISSN: 1432-0851
    Keywords: TNFα ; TNFβ ; sTNF-RI ; sTNF-RII ; Bladder cancer ; BCG immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intravesical immunotherapy for bladder cancer is the most effective form of tumour immunotherapy. Following repeated instillations of bacillus Calmette-Guerin (BCG) organisms into the bladder large quantities of several cytokines are detected in the urine. These cytokines include interleukins IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor α(TNFα), interferon γ(IFNγ) and also soluble intercellular adhesion molecule ICAM-1. In the work reported here we simultaneously quantified urinary levels of TNFα, TNFβ, TNF receptor I and TNF receptor II by enzyme-linked immunosorbent assay (ELISA) techniques and compared this with bioactive levels of TNF. This was undertaken with a limited number of patients throughout a course of six instillations of immunotherapy. Sequential instillations of BCG induced secretion of TNFα and TNFβ into urine. These cytokines were not always secreted simultaneously, perhaps suggesting differential regulation of their synthesis. Maximal concentrations of TNFα were 675 pg/ml and TNFβ 47 pg/ml. High levels of both species of soluble TNF receptor were readily identified in urine. Maximal levels of sTNF-RI were 6200 pg/ml (range from 0) and for sTNF-RII 7800 pg/ml (range from 0). Contrasting with earlier published observations concerning cytokine levels, the concentration of soluble receptor did not increase with repeated instillation. In apparent contrast with the ELISA data, very low levels of bioactive TNF were identified by the L929 bioassay (maximum concentration 1 U/ml) despite the elevated concentration of immunoreactive TNF. The large concentrations of soluble TNF receptor in patients' urine samples could account for the apparently low bioactivity as determined by the L929 cytotoxicity assay. The precise nature of the role of TNF in BCG immunotherapy remains undetermined; however, it is thought that proinflammatory cytokines are in part responsible for the clinical efficacy of this therapeutic approach. Whether other cytokines are antogonised by soluble binding proteins remains to be determined. Furthermore, whether TNF is bioactive in the bladder wall and only neutralised in the urine also requires investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01520294
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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