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(BCG)对表浅膀胱癌的抗肿瘤作用机制。我们先前认为，膀胱癌患者膀胱内注射卡介苗后尿白细胞的增加是由卡介苗引起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内诱导的这些细胞因子网络最终摧毁肿瘤的可能性，我们用原位杂交的方法检测了膀胱粘膜下形成的淋巴滤泡中每种细胞因子的mRNA，并临床评估了接受卡介苗免疫治疗的患者尿液中细胞因子浓度和膀胱癌复发率。在组织学上，卡介苗滴注后的膀胱粘膜下层可见淋巴滤泡和肉芽肿但由于不能在一年内掌握原位杂交技术，这些细胞因子不能直接在组织学上得到证实。然而，在临床上，经过近2年的随访发现，在卡介苗滴注后尿液中产生高浓度肿瘤坏死因子和G-CSF的患者，膀胱癌的复发较少。我们希望继续这项研究，以确认膀胱中的这些细胞因子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.