Bergenheim A T, Henriksson R, Piepmeier J M, Yoshida D
Department of Oncology, Umea University, Sweden.
J Neurooncol. 1996 Oct;30(1):81-9. doi: 10.1007/BF00177446.
Estramustine, a carbamate ester combining 17 beta-estradiol and nornitrogen mustard, has primarily been employed in the treatment of advanced prostatic carcinoma. However, a significant amount of preclinical investigation has been directed toward estramustine's activity against human malignant glioma. These studies have demonstrated that estramustine has potent antiproliferative effects against malignant glioma both in vitro and in vivo. Similar antimitotic effects also have been demonstrated for other carbamate esters. Estramustine does not impair proliferation of nonneoplastic astrocytes at concentrations that inhibit glioma cells. Although the reasons for this selective activity remain to be determined, it has been shown that malignant gliomas expresses an estramustine-specific binding site, estramustine-binding protein, more than brain tissue. In the clinical situation, an uptake and accumulation of estramustine in human glioma tissue have been demonstrated. Estramustine has been shown to enhance the cytotoxic effects of irradiation in relatively radioresistant glioma cells both in cell culture and in a rat glioma model. Estramustine has been regarded as mainly an anti-mitotic drug but recently other effects such as inhibition of DNA synthesis, induction of apoptosis, and membrane alterations have been shown. This report summarizes the preclinical observations concerning the effects of estramustine and related compounds on human malignant gliomas. These findings form the basis for proposing further laboratory and clinical investigation regarding estramustine and human malignant gliomas.
雌莫司汀是一种将17β-雌二醇与去甲氮芥结合的氨基甲酸酯，主要用于治疗晚期前列腺癌。然而，大量临床前研究已针对雌莫司汀对人类恶性胶质瘤的活性展开。这些研究表明，雌莫司汀在体外和体内对恶性胶质瘤均具有强大的抗增殖作用。其他氨基甲酸酯也显示出类似的抗有丝分裂作用。在抑制胶质瘤细胞的浓度下，雌莫司汀不会损害非肿瘤性星形胶质细胞的增殖。尽管这种选择性活性的原因尚待确定，但已表明恶性胶质瘤比脑组织表达更多的雌莫司汀特异性结合位点，即雌莫司汀结合蛋白。在临床情况下，已证实雌莫司汀在人类胶质瘤组织中存在摄取和蓄积。在细胞培养和大鼠胶质瘤模型中，雌莫司汀均已显示出可增强相对抗辐射的胶质瘤细胞对辐射的细胞毒性作用。雌莫司汀一直被视为主要的抗有丝分裂药物，但最近已显示出其他作用，如抑制DNA合成、诱导凋亡和膜改变。本报告总结了有关雌莫司汀及相关化合物对人类恶性胶质瘤作用的临床前观察结果。这些发现为提出关于雌莫司汀和人类恶性胶质瘤的进一步实验室和临床研究奠定了基础。
