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

类固醇脉冲疗法对胸腺瘤作用的潜在机制。

基本信息

批准号：
17591482
负责人：
KOBAYASHI Yoshihiro
金额：
$ 2.3万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591482/
关键词：
thymoma steroid apoptosis 胸腺種

项目摘要

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.

糖皮质激素已用于胸腺瘤。我们将胸腺瘤切片和婴儿胸腺在糖皮质激素的HOS培养（高氧浸没培养）下培养，发现肿瘤体积缩小的同时，CD 4 +8+双阳性的、表达高水平糖皮质激素受体的未成熟胸腺细胞明显减少。本实验采用体外胸腺瘤细胞培养方法，观察了5-氟尿嘧啶（5-FU）、顺铂（CDDP）、多西他赛（DOC）、卡铂（CBDCA）、紫杉醇（PTX）等药物对胸腺瘤细胞凋亡的影响。胸腺瘤术前激素冲击治疗和化疗的效果最显著，这可能与其对富含GR的CD 4 +8+双阳性未成熟淋巴细胞的特异性作用有关，提示激素冲击治疗可作为晚期胸腺瘤的诱导治疗，尤其是富含相关的CD 4 + CD 8+双阳性细胞的那些。胸腺瘤的术前诊断是必要的，这种治疗。胸腺瘤的组织学分类采用WHO分类法，流式细胞术分析与胸腺瘤相关的淋巴细胞以确定CD 4 + CD 8+双阳性细胞的比例将预测对类固醇脉冲治疗的反应。从针吸活检标本中回收的淋巴细胞的流式细胞术分析是用于此目的的有用措施。