STUDIES ON STIMULATION OF IMMUNOLOGICAL RESPONSES RESULTING FROM INTRAVESICAL BCG INSTILLATION IN PATIENTS WITH BLADDER CARCINOMAS

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  • 膀胱癌に対するBCG膀胱内注入療法における宿主免疫応答の賦活化に関する研究

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BCG immunotherapy for prevention and/or treatment of superficial bladder cancer has been highly successful. In general, BCG has been thought to be a non-specific immune stimulant. While the efficacy of BCG cannot be denied, the mechanism of action responsible for the beneficial results observed in the treatment of human bladder cancer remains largely undetermined. In this study, an attempt was made to determine whether intravesical BCG administration for the treatment of bladder tumors can stimulate systemic host immune responses such as PPD skin test reactivity, natural killer (NK) activity, antigen-dependent cell-mediated cytotoxicity (ADCC) and distribution of various lymphocyte markers. Local histological changes were also determined using conventional histology, electronmicroscopy and immunohistochemistry. A total of 35 patients who had histologically proved superficial transitional cell carcinoma of the bladder were given weekly intravesical BCG instillations for six weeks after transurethral resection of the tumor. Sixteen of the 35 patients were negative on the PPD skin test prior to BCG instillation. After BCG treatment, 14 of the 16 patients converted to a positive PPD skin test.<br>Increased NK activity and ADCC were observed in 14 of the 35 patients (40%) and 20 of the 35 patients (57.1%) after six BCG instillations, respectively. Increased percentages of Leu 7 and Leu 11 positive lymphocytes were noted following BCG instillation in 12 of the 35 patients (34.3%) and 14 of 35 patients (40%), respectively. Conventional histological examination revealed chronic inflammatory changes accompanied with submucosal infiltration of various inflammatory cells. In contrast to the evidence of increased systemic NK activity following BCG treatment, only seven of the 35 patients (20%) showed positive staining results against anti-Leu 7 antibody (NK) immunohistochemicaly. No significant positive staining against anti-BCG antibody was noted.<br>These results suggest that intravesical BCG instillation resulted in stimulation of host immune responses and may thus provide beneficial effects in the treatment or prevention of human bladder cancers. However, the mechanisms of anti-tumor effects on local immunological responses besides the stimulation of systemic immunological responses by intravesical BCG instillation remain undetermined.

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