AROMATASE INHIBITORS, BREAST CANCER, AND OTHER DISEASES

4-OHA，一种有效和选择性的雌激素生物合成抑制剂， 将被合成用于以下研究。评估 提出了4-OHA在乳腺癌患者中的作用。 在之前的研究中，29%的对4-OHA有反应的患者没有 对以前的抗雌激素治疗(他莫昔芬)有反应，而 另有50%的患者曾因内分泌治疗而复发。这个 肿瘤芳香酶对肿瘤生长的意义将是 通过使用敏感的免疫细胞化学检测 最新制备的过氧化物酶-抗过氧化物酶(PAP)技术 芳香酶的多克隆抗体。抗雌激素和抗雌激素抗体 黄体酮受体将应用于相同的组织 为比较做准备。雌酮，雌二醇的浓度， 硫酸雌酮和雄激素前体将在 肿瘤样本。C-ras/H癌基因蛋白对肿瘤细胞生长的影响 激素依赖和激素非依赖性肿瘤生长将 也可以通过上述技术进行调查。的表达方式 致癌蛋白(P21)将在肿瘤样本中被检测。 芳香酶治疗前和治疗中患者的情况 抑制剂。 与上述类似的体外研究将在组织中进行。 来自良性前列腺增生症和前列腺癌患者 癌症。前列腺组织也将在裸鼠体内生长， 4-OHA对肿瘤生长的影响。

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.