Ohwada S, Ogawa T, Izumi M, Inoue T, Teshigawara O, Ikeya T, Kusaba T, Roppongi T, Iino Y, Morishita Y
Second Department of Surgery, Gunma University School of Medicine, Japan.
Anticancer Res. 1997 May-Jun;17(3C):2313-8.
The purpose of the study was to verify whether OK-432 in combination with 5'-DFUR induced thymidine phosphorylase (TdR Pase) and cytokines in gastric cancer patients as well as in vitro.
Fifty patients with invasive gastric cancer were randomly assigned, upon admission using by a closed-envelope technique, to either a group receiving 5'DFUR or OK-432 alone, to a group receiving both 5'DFUR and OK-432, or to a non- treated group up. Surgical specimens of the tumor and normal tissues were taken soon after gastrectomy to evaluate TdR Pase activity, IL-1 alpha and TNF-production.
TdR Pase activities were several times higher in tumor than in normal tissues. In normal tissues, TdR Pase activities in the 5'-DFUR + OK-432 group were significantly higher than in the OK-432 group. TdR Pase activity in tumors, however, showed no significant difference between treated group. In the 5'-DFUR + OK-432 group, the level of IL-1 alpha production in tumor was significantly higher compared to the control group. In the 5'-DFUR + OK-432 group, the level of TNF alpha production in tumor was significantly higher than in normal tissue. TNF alpha production in tumor showed no significant difference in each treated group compared to the control. There was a significant correlation between TdR Pase activity and IL-1 alpha production levels in tumor.
TdR Pase was induced by IL-1 alpha in tumor tissues of gastric cancer patients. OK-432 in combination with 5'-DFUR, however, did not induce TNF alpha and IL-1 alpha, and increase TdR Pase activity in gastric cancer tumors.
本研究的目的是验证沙培林（OK-432）联合5'-脱氧氟尿苷（5'-DFUR）是否能在胃癌患者体内及体外诱导胸苷磷酸化酶（TdR Pase）和细胞因子的产生。
50例浸润性胃癌患者入院时采用封闭信封技术随机分组，分别为单独接受5'-DFUR或沙培林的组、接受5'-DFUR和沙培林两者的组或未治疗组。胃切除术后立即获取肿瘤及正常组织的手术标本，以评估TdR Pase活性、白细胞介素-1α（IL-1α）和肿瘤坏死因子（TNF）的产生。
肿瘤组织中TdR Pase活性比正常组织高几倍。在正常组织中，5'-DFUR + 沙培林组的TdR Pase活性显著高于沙培林组。然而，肿瘤组织中的TdR Pase活性在各治疗组之间无显著差异。在5'-DFUR + 沙培林组中，肿瘤组织中IL-1α的产生水平显著高于对照组。在5'-DFUR + 沙培林组中，肿瘤组织中TNFα的产生水平显著高于正常组织。与对照组相比，各治疗组肿瘤组织中TNFα的产生无显著差异。肿瘤组织中TdR Pase活性与IL-1α产生水平之间存在显著相关性。
在胃癌患者的肿瘤组织中，IL-1α可诱导TdR Pase。然而，沙培林联合5'-DFUR并未诱导胃癌肿瘤组织中TNFα和IL-1α的产生，也未增加TdR Pase活性。
