AROMATASE INHIBITORS, BREAST CANCER, AND OTHER DISEASES

4-OHA，雌激素生物合成的有效和选择性抑制剂， 将被合成用于以下研究。 评价 4-OHA在乳腺癌患者中的作用。 在以前的研究中，29%对4-OHA有反应的患者没有 对既往抗雌激素治疗（他莫昔芬）有反应， 另外50%的患者曾因内分泌治疗而复发。 的 肿瘤芳香化酶对肿瘤生长的意义将是 用敏感的免疫细胞化学法测定 过氧化物酶-抗过氧化物酶（PAP）技术， 芳香化酶的多克隆抗体。 雌激素抗体和 孕酮受体将被应用于相同的组织 准备比较。 雌酮，雌二醇， 硫酸雌酮和雄激素前体将在 肿瘤样本 c-ras/H癌基因蛋白对肝癌细胞凋亡的影响 激素依赖性和激素非依赖性肿瘤生长将 也可以通过上述技术进行研究。 的表达 将在肿瘤样品中测定致癌蛋白（p21 在用芳香酶治疗之前和治疗期间， 抑制剂. 将在组织中进行与上述相似的体外研究 来自良性前列腺肥大和前列腺增生患者 癌 前列腺组织也将在裸鼠中生长， 测定4-OHA对肿瘤的作用。

4-OHA, a potent and selective inhibitor of estrogen biosynthesis, will be synthesized for use in the following studies. Evaluation of the effect of 4-OHA in breast cancer patients are proposed. In previous studies, 29% of patients responding to 4-OHA had not respond to previous antiestrogen treatment (tamoxifen) while a further 50% had relapsed for prior endocrine therapy. The significance of tumor aromatase to tumor growth will be determined by using the sensitive immunocytochemical peroxidase-antiperoxidase (PAP) technique with recently prepared polyclonal antibodies to aromatase. Antibodies to estrogen and progesterone receptors will be applied to the same tissue preparation for comparison. Concentrations of estrone, estradiol, estrone sulfate and androgen precursors will be measured in the tumor samples. The influences of c-ras/H oncogenic protein on hormone-dependent and hormone independent tumor growth will also be investigated by the above technique. The expression of the oncogenic protein (p21) will be determined in tumor samples from patients before and during treatment with aromatase inhibitor. Similar in vitro studies to the above will be carried out in tissue from patients with benign prostatic hypertrophy and prostatic cancer. Prostatic tissues will also be grown in nude mice and the effect of 4-OHA on the tumors determined.