| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
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.
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