THE STUDY ON THE MECHANISM OF THE ANTITUMOR EFFECT OF BACILLUS CALMETTE-GUERIN(BCG) IMMUNOTHERAPY FOR SUPERFICIAL BLADDER CANCER.

本研究旨在阐明卡介苗（bacillus Calmette-Guerin， BCG）对浅表性膀胱癌的抗肿瘤作用机制。我们之前提出膀胱内灌注卡介苗后膀胱内尿白细胞的增加是由卡介苗诱导的粘膜下免疫反应产生的各种细胞因子引起的。为了阐明卡介苗在膀胱中诱导的这些细胞因子网络最终破坏肿瘤的可能性，我们通过原位杂交检测了膀胱粘膜下形成的淋巴泡中活化淋巴细胞中每种细胞因子的mRNA，并临床评估了接受卡介苗免疫治疗的患者尿液细胞因子浓度和膀胱癌复发率。卡介苗灌注后膀胱粘膜下层组织学上可见卡介苗迟发性超敏反应引起的淋巴滤泡和肉芽肿，但由于我们一年内还不能掌握原位杂交技术，这些细胞因子不能直接组织学上可见。然而，在临床上，通过近2年的随访显示，在卡介苗灌注后尿液中高浓度产生肿瘤坏死因子（TNF）和G-CSF的患者膀胱癌复发的频率较低。我们希望继续这项研究，以证实膀胱中这些细胞因子的网络有助于肿瘤的破坏。

This study was designed to clarify the mechanism of the antitumor effect of bacillus Calmette-Guerin(BCG) on superificial bladder cancer. We previously suggested that the increase in urinary leukocytes observed after intravesical instillation of BCG in patients with bladder cancer was caused by various cytokines produced by submucosal immunological reactions induced by the instillation of BCG.To clarify the possibility that a network of these cytokines in the bladder induced by BCG instillation eventually destroys the tumor, we examined the mRNA for each cytokine in activated lymphocytes in lymph follicles formed submucosally in the bladder by in situ hybridization, and clinically evaluated the urinary cytokine concentrations and the recurrence rate of bladder cancer in patients who underwent BCG immunotherapy.Lymph follicles and granulomas due to delayd hypersensitivity reaction to BCG could be demonstrated histologically in the submucosa of the bladder after BCG instillation, but these cytokines could not be directly demonstrated histologically, because we could not master the technique of in situ hybridization within the year. Clinically, however, recurrence of bladder cancer was shown to be less frequent in patients in whom tumor necrosis factor(TNF) and G-CSF were produced at high concentrations in urine after BCG instillation by a followup of nearly 2 years.We would like to continue this study to confirm that a network of these cytokines in the bladder contributes to the destruction of the tumor.