Kobayashi Yoshihiro, Fujii Yoshitaka, Yano Motoki, Sasaki Hidefumi, Yukiue Haruhiro, Haneda Hiroshi, Suzuki Eriko, Endo Katsuhiko, Kawano Osamu
Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan.
Cancer. 2006 May 1;106(9):1901-7. doi: 10.1002/cncr.21875.
Glucocorticoid was used in thymomas. The purpose of the study was to evaluate the efficacy of intravenous high-dose glucocorticoid (steroid pulse) therapy in patients with previously untreated advanced thymoma. Causes were also sought for a possible underlying mechanism of the effect of steroid on thymoma.
Seventeen patients with invasive thymoma who had not received previous chemotherapy or radiation therapy were enrolled in the study. All cases were treated with 2 courses of glucocorticoid therapy before surgery. Tumor response was assessed by computed tomography (CT) scan 1 week after the steroid pulse therapy. Lymphocytes associated with thymoma were analyzed for their CD4/CD8 phenotype and glucocorticoid receptor (GR). TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining was used to analyze the apoptotic lymphocytes and epithelial cells.
The overall response rate to the steroid pulse therapy was 47.1% (8 of 17). The reduction in tumor size was most prominent in type B1 thymomas; there were significant differences between type AB and type B1 thymomas (P = .0234) and type B1 and type B3 thymomas (P = .0068). 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 after glucocorticoid therapy.
The efficiency of preoperative steroid pulse therapy in type B1 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.
糖皮质激素被用于胸腺瘤治疗。本研究旨在评估静脉注射大剂量糖皮质激素(类固醇冲击)疗法对既往未接受治疗的晚期胸腺瘤患者的疗效。同时还探寻了类固醇对胸腺瘤产生作用的潜在机制。
17例未接受过化疗或放疗的侵袭性胸腺瘤患者纳入本研究。所有病例在手术前均接受2个疗程的糖皮质激素治疗。类固醇冲击治疗1周后通过计算机断层扫描(CT)评估肿瘤反应。分析胸腺瘤相关淋巴细胞的CD4/CD8表型和糖皮质激素受体(GR)。采用TdT介导的dUTP生物素缺口末端标记(TUNEL)染色分析凋亡的淋巴细胞和上皮细胞。
类固醇冲击治疗的总体缓解率为47.1%(17例中的8例)。肿瘤大小缩小在B1型胸腺瘤中最为显著;AB型与B1型胸腺瘤之间(P = 0.0234)以及B1型与B3型胸腺瘤之间(P = 0.0068)存在显著差异。肿瘤大小缩小伴随着表达较高水平糖皮质激素受体的CD4+8+双阳性未成熟胸腺细胞显著减少。糖皮质激素治疗后,肿瘤上皮细胞和淋巴细胞成分均出现凋亡变化。
术前类固醇冲击治疗在B1型胸腺瘤中的疗效最为显著,这可能与对富含GR的CD4+8+双阳性未成熟淋巴细胞的特异性作用有关,这类细胞在该型胸腺瘤中大量存在。