摘要
目的：目前乳腺癌的发病率越来越高，每年大约新发病例约130万，死亡率也在逐年上升，乳腺癌已经成为严重威胁广大妇女生命安全的主要疾病之一。关于乳腺癌的治疗除常规手术、放、化疗以外，内分泌的治疗越来越受到大家的重视，在美国内分泌治疗已占55％左右，在日本大约20％左右，而我国仅占4％，但目前内分泌治疗药物如三苯氧胺、芳香化酶抑制剂的疗效已经得到大家确认，但其本身又具有很多副作用，如三苯氧胺可导致子宫内膜增厚，甚至子宫内膜癌，可导致血脂升高，血栓形成，脂肪肝，而芳香化酶抑制剂仅限于绝经以后患者，长期服用可导致骨质破坏，能否发现一种效果好副作用少的内分泌药物这是本研究的出发点。米非司酮(mifepristone，MIF)是1981年由法国Roussel Uclaf药厂首家生产的一种19-去甲睾酮的衍生物，对孕激素受体(progesterone receptor，PR)、糖皮质激素受体(glucocorticoid receptor，GR)有很强的亲和力。MIF是复合型拮抗剂，一方面，其与受体竞争性结合，表现为抗孕激、抗糖皮质激素作用；另一方面，又表现为部分孕激(progesterone，P)、糖皮质激素(glucocorticoid，G)样作用。近年发现，MIF具有抗肿瘤、增强抗癌药物疗效及其它新用途。孕激素在体外实验中有刺激乳腺癌细胞增殖的作用，可能与乳腺癌的转移有关，而MIF为孕激素受体拮抗剂，故可用于乳腺癌治疗。体外实验发现孕激素拮抗药或孕激素受体调节药与抗雌激素或芳香化酶抑制药联合作用比单一作用有更强的抗肿瘤作用。有实验证明米非司酮对PR阳性的乳腺癌细胞有抑制作用，其疗效接近于卵巢去势或三苯氧胺(TAM)。以往多认为MIF的抗肿瘤作用与抗孕激素有关，但是其在PR(-)肿瘤中表现出的抗肿瘤作用表明，MIF的抗肿瘤作用不是抗孕激素单一作用的结
OBJECTIVE: Attack rate of breast cancer is more and more at present time,as about 1,300,000 new case and a rising death rate ever year. Breast cancer has become one of the principal diseases that threate the life of women severely. Besides conventional operation、 radiotherapy、 chemoth- erapy, endocrine therapy is reconstructed increasingly. Endocrine therapy occupies about 55 percent in American,20 percent in Japan and only 4 percent in China. Now, therapeutic effect of endocrine therapy medicines, such as tamoxifen(TAM)、 fadrozol,have been affirmed,but itself have many side effects, e.g. TAM's endometrium thickening、 even endometrial cancer and high blood fat、 thrombogenesis、 adiposis hepatica, fadrozol's destruction of bone. To find a effective、 little adverse reaction endocrine therapy medicine is the starting point of our study.
In 1981,mifepristone(MIF) a derivation of 19-nortestosterone,was first produced by Roussel Uclaf, France,and has drastic chemical force to progesteronereceptor(PR) and glucocorticoidreceptor(GR). MIF is a multiplicity antagon, at first,it shows antiprogesterone and antiglucocorti- coid,second it shows progesterone(P)、 glucocorticoid(G) effect partly. Recent years had find MIF has antitumer effect and can reinforce the therapeutic effect of anticancer drugs and other uses. P can stimulate proliferation of breast cancer cells in vitro,this may relate to breast cancer metastasis. AS receptor antagonis of P, MIF can be used in the treatment of breast cancer. In vitro, the investigators showed that the
引文
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