ESTABLISHMENT OF TECHNIQUE TO ESTIMATE THE MOST APPROPRIATE METHOD OF ENDOCRINE THERAPY FOR PROSTATE CANCER

许多方法已被用于前列腺癌的内分泌治疗，如手术阉割、LHRH激动剂、最大雄激素阻断、抗雄激素单一疗法和雌激素。此外，即使雄激素抑制没有更多的效果，也进行了几种激素操作，包括停用抗雄激素和给予糖皮质激素。然而，很难在治疗前估计出最适合每个患者的方法。因此，为了建立确定内分泌治疗方案的方法，我们检测了前列腺癌患者接受内分泌治疗后的血清标志物、遗传变化和组织病理学特征与预后的关系。预处理血清睾酮水平和雄激素受体CAG重复数是良好的预后因素。血清嗜铬粒蛋白A水平高、血清前列腺特异性抗原（PSA）水平低的患者预后较差，伴有神经内分泌分化。间歇性雄激素抑制可能与雄激素依赖性肿瘤患者有关，在这些患者中，雄激素抑制能够通过细胞凋亡导致肿瘤缩小。在间歇治疗期间，血清PSA的游离总比可用于确定重新开始治疗的时间。地塞米松治疗对雄激素抑制后出现进展的患者有效，可能是通过降低血清白细胞介素-6水平来抑制雄激素受体的配体非依赖性激活。根据患者和肿瘤的临床病理和遗传因素，进行有序的内分泌治疗，选择最合适的内分泌治疗方法。

A number of methods have been utilzed as endocrine therapy for prostate cancer, such as surgical castration, LHRH agonist, maximum androgen blockade, antiandrogen-monotherapy, and estrogen. In addition, several hormonal manipulations including withdrawal of antiandrogen and administration of glucocorticoid have been performed even when androgen suppression reveals no more effect. However, it is difficult to estimate the most appropriate method for each patient before the treatment. Thus, to establish the technique for determining the suitable endocrine therapy, serum markers, genetic changes and histopathological characteristics were examined in relation to prognosis in prostate cancer patients treated with endocrine therapy. Pretreatment serum testosterone level and the number of CAG repeat in the androgen receptor were shown to be good prognostic factors. Patients with high level of , serum chromogranin A and low serum prostate specific antigen (PSA) demonstrated poor prognosis along with neuroendocrine differentiation. Intermittent androgen suppression could be implicated for patients with androgen-dependent tumors, in whom androgen suppression were able to result in tumor shrinkage through apoptosis. During intermittent therapy, free-to-total ratio of serum PSA was useful to determine the timing of restart of therapy. Dexamethasone therapy was effective for patients who showed progression after androgen suppression, probably through inhibition of ligand-independent activation of the androgen receptor by decreasing serum interleukin-6 level. The order-made endocrine therapy to select the most appropriate method of endocrine therapy could be achieved based on clinicopathological and genetic factors in both patients and tumors.