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[合成索状因子6,6'-二-O-癸酰基-α,α-海藻糖(SS 554)对小鼠的抗肿瘤作用]

[Antitumor effect of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha, alpha-trehalose (SS 554) in mice].

作者信息

Kohya H, Ishii F, Takano S, Katori T, Ebina T, Ishida N

出版信息

Gan To Kagaku Ryoho. 1986 May;13(5):1897-904.

PMID:3754712
Abstract

The antitumor effect of a synthetic cord factor (6, 6'-Di-O-decanoyl-alpha, alpha-trehalose) (SS 554) on the growth of Meth-A fibrosarcoma in BALB/c mice was examined. With regard to administration routes, only intratumoral (i.t.) injection showed a curative effect; subcutaneous (s.c.), per oral (p.o.) or intravenous (i.v.) routes has no such effect. To show the antitumor effect of known natural and synthetic cord factors, the co-presence of oily vehicles has been shown to be necessary. Accordingly, compound SS 554 examined in suspensions of sesame oil, squalane (SQA), squalene (SQE) or sesame oil and water emulsion had a curative effect with a 60% survival rate. However, no such effect was obtained with a suspension in PBS or in HCO-60 solution. In this regard, it should be noted that sequential but independent administration of SS 554 and oil was found to be equally as effective as simultaneous administration of oil with SS 554. Thus the effect of the oil should be reconsidered through an examination of the sequential appearance of effector cells. In the case of sesame oil, the amount of oil necessary was over 10%, or 0.01 mg absolutely. When the dose effect of SS 554 was examined in the presence of 10% sesame oil, doses over 1 mg exhibited a dose dependent curative effect. In tumor-bearing mice, the effect of the time of administration was also examined; the best result was obtained when intratumor injection was performed on day 3 after tumor implantation. Mice that recovered after SS 554 treatment exhibited growth inhibition and rejection of rechallenged Meth-A cells. However, this immunity was specific as it did not extend to a rechallenge with RL male-1 leukemia cells.

摘要

研究了合成的索状因子(6,6'-二-O-癸酰基-α,α-海藻糖)(SS 554)对BALB/c小鼠体内Meth-A纤维肉瘤生长的抗肿瘤作用。关于给药途径,只有瘤内(i.t.)注射显示出治疗效果;皮下(s.c.)、口服(p.o.)或静脉内(i.v.)给药途径均无此效果。为了显示已知天然和合成索状因子的抗肿瘤作用,已证明油性载体的共同存在是必要的。因此,在芝麻油、角鲨烷(SQA)、角鲨烯(SQE)或芝麻油与水乳液的悬浮液中检测的化合物SS 554具有治疗效果,存活率为60%。然而,在PBS或HCO-60溶液中的悬浮液未获得此效果。在这方面,应注意到,SS 554和油的顺序但独立给药与油与SS 554同时给药同样有效。因此,应通过检查效应细胞的顺序出现来重新考虑油的作用。就芝麻油而言,所需的油量超过10%,或绝对量为0.01 mg。当在10%芝麻油存在下检测SS 554的剂量效应时,超过1 mg的剂量表现出剂量依赖性治疗效果。在荷瘤小鼠中,还研究了给药时间的影响;在肿瘤植入后第3天进行瘤内注射时获得了最佳结果。经SS 554治疗后恢复的小鼠表现出生长抑制和对再次接种的Meth-A细胞的排斥。然而,这种免疫是特异性的,因为它不会扩展到对RL male-1白血病细胞的再次接种。

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