17 research outputs found

    Role of urothelial cells in BCG immunotherapy for superficial bladder cancer

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    Intravesical instillation of Bacillus Calmette-Guérin (BCG) is used for the treatment of superficial bladder cancer, both to reduce the recurrence rate of bladder tumour and to diminish the risk of progression. Since its first therapeutic application in 1976, major research efforts have been directed to decipher the exact mechanism of action of the BCG-associated antitumour effect. Bacillus Calmette-Guérin causes an extensive local inflammatory reaction in the bladder wall. Of this, the massive appearance of cytokines in the urine of BCG-treated patients stands out. Activated lymphocytes and macrophages are the most likely sources of these cytokines, but at present other cellular sources such as urothelial tumour cells cannot be ruled out. Bacillus Calmette-Guérin is internalised and processed both by professional antigen-presenting cells and urothelial tumour cells, resulting in an altered gene expression of these cells that accumulates in the presentation of BCG antigens and secretion of particular cytokine

    Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice

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    The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as Mycobacterium brumae, and/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and/or the preparation remain unknown. In an orthotopic murine BC model, local immune responses were assessed by measuring immune cells into the bladder and macromolecules in the urine by flow cytometry and multiplexing, respectively. Systemic immune responses were analyzed by quantifying sera anti-mycobacteria antibody levels and recall responses of ex vivo splenocytes cultured with mycobacteria antigens. In both BCG- and M. brumae-treated mice, T, NK, and NKT cell infiltration in the bladder was significantly increased. Notably, T cell infiltration was enhanced in OO-in-water emulsified mycobacteria-treated mice, and urine IL-6 and KC concentrations were elevated. Furthermore, mycobacteria treatment augmented IgG antibody production and splenocyte proliferation, especially in mice receiving OO-in-water emulsified mycobacteria. Our data demonstrate that intravesical mycobacterial treatment triggers local and systemic immune responses, which are most significant when OO-in-water emulsified mycobacteria are used

    Testicular microlithiasis, a premalignant condition: Prevalence, histopathologic findings, and relation to testicular tumor

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    Objectives. To perform a retrospective analysis concerning the prevalence of testicular microlithiasis (TMJ. in patients with TM, the association of TM with testicular tumor, histopathologic findings, and follow-up were studied. Methods. During a 6-year period at the Central Military Hospital or the University Medical Center in Utrecht, The Netherlands, ultrasonography of the testis was performed in 1535 patients. Patient records, ultrasound images, and histopathologic specimens were reviewed. Follow-up was performed in patients with TM. Results. In 63 patients (4.1%), with a mean age of 35.4 years (range 19 to 74), TM was diagnosed at ultrasonography. In 29 of these patients (46%), a concomitant testicular tumor was diagnosed. A statistically significant correlation was found between TM and the presence of a testicular tumor (P Conclusions, A correlation was found between TM and testicular tumor. Because an increasing number of studies have reported patients with TM who developed a testicular tumor, TM should be regarded as a premalignant condition, which necessitates follow-up. Urologists should consider testis biopsy in patients with TM. UROLOGY 57: 1133-1137, 2001. (C) 2001, Elsevier Science Inc
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