The underlying mechanism of the effect of steroid pulse therapy on thymoma.

糖皮质激素已被用于治疗胸腺瘤。然而，类固醇对胸腺瘤的作用机制尚不清楚。我们用糖皮质激素对切片胸腺瘤和婴儿胸腺进行高氧培养。肿瘤大小的减小伴随着CD4+8+双阳性未成熟胸腺细胞的显著减少，这些细胞表达更高水平的糖皮质激素受体。糖皮质激素作用后，肿瘤上皮细胞和淋巴细胞成分均发生凋亡改变。体外培养胸腺瘤药物：5-氟尿嘧啶（5-FU）、顺铂（CDDP）、多西紫杉醇（DOC）、卡铂（CBDCA）、紫杉醇（PTX）。肿瘤上皮细胞和淋巴细胞均可见凋亡改变。术前类固醇脉冲治疗和化疗在胸腺瘤中的效果最为突出，这可能与对该类胸腺瘤中丰富的富含GR的CD4+8+双阳性未成熟淋巴细胞的特异性作用有关。我们建议类固醇脉冲疗法可以作为晚期胸腺瘤的诱导疗法，特别是那些富含相关CD4+CD8+双阳性细胞的胸腺瘤。胸腺瘤的术前诊断对这种治疗至关重要。胸腺瘤的组织学分类采用WHO分类和流式细胞术分析胸腺瘤相关淋巴细胞，以确定CD4+CD8+双阳性细胞的比例，预测对类固醇脉冲治疗的反应。流式细胞术分析从针活检样本中回收的淋巴细胞是一种有用的测量方法。

Glucocorticoid has been used in thymomas. However, the mechanism of steroid action on thymomas is not clear.We cultured sliced thymoma and infant thymus in glucocorticoid under HOS culture (high oxygen submersion culture).The reduction in tumor size was accompanied with a marked reduction in the CD4+8+ double positive immature thymocytes that expressed higher levels of glucocorticoid receptor. Apoptotic changes were observed in both neoplastic epithelial cell and lymphocyte components following glucocorticoid.We cultured thymoma in vitro under drugs, 5-fluoroucil(5-FU), cisplatin(CDDP), docertaxel(DOC), carboplatin(CBDCA), paclitaxel(PTX). Apoptotic changes were also observed in both neoplastic epithelial cell and lymphocyte.The efficiency of pre-operative steroid pulse therapy and chemotherapy in thymoma was most prominent which is probably related to the specific effect on GR rich CD4+8+ double positive immature lymphocytes which are abundant in this type of thymoma.We propose that steroid pulse therapy can be used as induction therapy for advanced thymoma, especially those rich in associated CD4+CD8+ double positive cells. Preoperative diagnosis of thymoma is essential for this treatment. Histological classification of thymoma using WHO classification and flow cytometric analysis of the lymphocytes associated with thymoma to determine the proportion of CD4+CD8+ double positive cells will predict the response to the steroid pulse therapy. Flow cytometric analysis oflymphocytes recovered from needle biopsy samples is a useful measure for this purpose.