Deguchi M, Isobe Y, Matsukawa S, Yamaguchi A, Nakagawara G
Department of Surgery I, Fukui Medical University, Japan.
Surgery. 1998 Apr;123(4):440-9.
One causative factor of tumor metastasis enhanced by surgical stress is thought to be hypersecretion of endogenous glucocorticoids. This study evaluated the effectiveness of metyrapone treatment and adrenalectomy in preventing the harmful effects of glucocorticoids in the enhancement of tumor metastasis resulting from surgical stress.
The effect of dexamethasone on pulmonary metastasis of MRMT-1 cells and on the number of peripheral lymphocytes was evaluated in rats. To evaluate the suppressive effect of adrenalectomy and metyrapone treatment on operation-induced enhancement of metastasis, several parameters such as induction of pulmonary metastasis, serum corticosterone levels, and the number of blood lymphocytes and apoptotic thymocytes were determined.
With dexamethasone treatment, the number of peripheral lymphocytes rapidly decreased; in contrast, pulmonary metastasis increased. The serum corticosterone level was doubled at 1 hour, apoptotic thymocyte numbers were increased about sevenfold at 3 hours and about fourfold at 6 hours, and blood lymphocyte numbers were decreased at 3 hours after laparotomy, which facilitated about a 10-fold increase in the pulmonary metastasis. These changes were almost completely suppressed by preoperative adrenalectomy and metyrapone treatment.
Preoperative metyrapone treatment, which suppresses hypersecretion of endogenous glucocorticoids as a result of operation, modulates the enhancement of cancer metastases and may be an effective treatment.
手术应激增强肿瘤转移的一个致病因素被认为是内源性糖皮质激素分泌过多。本研究评估了甲吡酮治疗和肾上腺切除术在预防糖皮质激素对手术应激导致的肿瘤转移增强的有害影响方面的有效性。
在大鼠中评估地塞米松对MRMT - 1细胞肺转移及外周淋巴细胞数量的影响。为评估肾上腺切除术和甲吡酮治疗对手术诱导的转移增强的抑制作用，测定了几个参数，如肺转移的诱导、血清皮质酮水平、血液淋巴细胞数量和凋亡胸腺细胞数量。
用地塞米松治疗后，外周淋巴细胞数量迅速减少；相反，肺转移增加。剖腹术后1小时血清皮质酮水平加倍，3小时凋亡胸腺细胞数量增加约7倍，6小时增加约4倍，3小时血液淋巴细胞数量减少，这促进了肺转移增加约10倍。术前肾上腺切除术和甲吡酮治疗几乎完全抑制了这些变化。
术前甲吡酮治疗可抑制手术导致的内源性糖皮质激素分泌过多，调节癌症转移的增强，可能是一种有效的治疗方法。
