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生长抑素类似物善得定(SMS201-995)治疗二甲基苯并蒽诱导的大鼠乳腺肿瘤

The somatostatin analog Sandostatin (SMS201-995) in treatment of DMBA-induced rat mammary tumors.

作者信息

Bakker G H, Setyono-Han B, Foekens J A, Portengen H, van Putten W L, de Jong F H, Lamberts S W, Reubi J C, Klijn J G

机构信息

Division of Endocrine Oncology (Biochemistry and Endocrinology), Dr. Daniel Den Hoed Cancer Center, Rotterdam, The Netherlands.

出版信息

Breast Cancer Res Treat. 1990 Nov;17(1):23-32. doi: 10.1007/BF01812681.

Abstract

The effects of treatment with a somatostatin analog (Sandostatin, SMS201-995) were investigated in female rats with dimethylbenzanthracene (DMBA)-induced rat mammary tumors. A 3-week treatment was performed using sandostatin, the LHRH-agonist buserelin alone, or buserelin in combination with sandostatin. Twice daily sandostatin treatment was performed with dosages of 0.05 microgram, 0.2 microgram, 1 microgram, 5 micrograms, and 20 micrograms. Buserelin was used in a 2 x 5 micrograms/day dosage. The combined results from six different experiments show that the various dosages of sandostatin caused no tumor growth inhibition. Somatostatin receptors could not be demonstrated in these mammary tumors. Sandostatin treatment by daily injections did not suppress levels of growth hormone, prolactin, or epidermal growth factor-like activities. Estrogen (ER) and progesterone (PgR) receptor contents of the mammary tumors were not changed. In contrast, buserelin treatment caused highly significant tumor remission. The combined treatment with sandostatin and buserelin did not alter the treatment results obtained after treatment with buserelin alone. In conclusion, sandostatin treatment in this tumor model had no direct growth inhibitory effect and did not cause an endocrine inhibition of mammary tumor growth. However, these results do not exclude antitumor effects in human breast cancer in view of the presence of somatostatin receptors in approximately 20-45% of human tumors, besides possible different endocrine effects.

摘要

研究了生长抑素类似物(善得定,SMS201 - 995)对二甲基苯并蒽(DMBA)诱导的雌性大鼠乳腺肿瘤的治疗效果。使用善得定、单独使用促性腺激素释放激素(LHRH)激动剂布舍瑞林或布舍瑞林与善得定联合进行为期3周的治疗。善得定每日两次给药,剂量分别为0.05微克、0.2微克、1微克、5微克和20微克。布舍瑞林的使用剂量为每天2×5微克。六个不同实验的综合结果表明,不同剂量的善得定均未引起肿瘤生长抑制。在这些乳腺肿瘤中未检测到生长抑素受体。每日注射善得定并未抑制生长激素、催乳素或表皮生长因子样活性的水平。乳腺肿瘤的雌激素(ER)和孕激素(PgR)受体含量未发生变化。相比之下,布舍瑞林治疗导致肿瘤显著缓解。善得定与布舍瑞林联合治疗并未改变单独使用布舍瑞林后的治疗效果。总之,在该肿瘤模型中,善得定治疗没有直接的生长抑制作用,也未引起对乳腺肿瘤生长的内分泌抑制。然而,鉴于约20 - 45%的人类肿瘤中存在生长抑素受体,以及可能存在的不同内分泌效应,这些结果并不排除善得定对人类乳腺癌的抗肿瘤作用。

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