前列腺癌是泌尿系統疾病中，最常見的惡性腫瘤病變，在其發生的過程中有許多複雜的因子參與。目前已知有許多去毒性有關的酵素或是生長因子，可能與前列腺癌的形成有關。本實驗第一部分的實驗目的係探討glutathione S-transferase M1 (GST M1)、 insulin-like growth factors-2 (IGF-2)以及epidermal growth factor (EGFR)等因子的基因之多形性是否可以被做為前列腺癌臨床上鑑別診斷的標誌。在本研究中﹐把來自相同區域的96位前列腺癌病人的GST M1，IGF-2和EGFR基因多型性的發生頻率與121個健康的男性志願者做比較(受檢驗之男性年齡皆大於六十歲)。研究結果發現，前列腺癌病人與健康的男性在GST M1之基因型上有明顯的不同(p = 0.042)；在前列腺癌病人組中缺少GST M1之基因者有59.4 %，顯著高於對照組中健康男性出現的比率(45.5 %)。然而，在IGF-2與EGFR方面兩組之間並沒有顯著之差異。根據此項研究發現，在台灣男性族群之中，GST M1基因之多型性可能與前列腺癌的發生機率有關。
第二部分之實驗目的乃在觀察FK228對前列腺腫瘤細胞生長之影響。在動物實驗中發現每週三次餵食NOD-SCID鼠50 mg/kg FK228，抑制腫瘤生長和轉移。腫瘤退化超過25 % 並增進存活率。移植前列腺腫瘤細胞之NOD-SCID鼠所長出之腫瘤體積平均為2 cm3，在實驗進行到一半時平均腫瘤體積為0.8 ± 0.18 cm3，在肺部也可以發現大量前列腺專一抗原的表現，表示有大量的癌細胞轉移至肺部。至於餵食FK228之前列腺腫瘤細胞轉殖NOD-SCID鼠在實驗進行中間，其腫瘤體積平均為0.37 ± 0.1 cm3，實驗終止時其肺部的組織未發現有癌細胞浸潤或是轉移的情形。進一步發現，餵食FK228之老鼠腫瘤細胞表現較多的PSA、Bax與p21，由此及電子顯微鏡檢驗推斷，FK228可以促使腫瘤細胞分化，並且進行程序性凋亡，減少腫瘤細胞之肺轉移。餵食小劑量50 mg/kg 每週三次或一次劑量1.2 g/kg FK228 並無負面影響且前者顯著產生抗癌活性。
實驗結果顯示GST M1 基因在臺灣族群可能與前列腺癌發生有關。而FK228 可能對前列腺癌症患者之治療具有相當的價值。

Prostate cancer is the most common urological malignancy involving multiple factors. Enzymes for detoxification and growth factors might also play a role in the formation of prostate cancer. The aim of part one study was to investigate whether polymorphisms of glutathione S-transferase M1 (GST M1), insulin-like growth factor-2 (IGF-2) and epidermal growth factor (EGFR) genes could be used as genetic markers for association with prostate cancer. We compared the frequency of the polymorphisms of GST M1, IGF-2, and EGFR genes between 96 patients with prostate cancer and 121 healthy male volunteers from the same area (age, > 60 years). There was significant distribution of the genotype of GST M1 gene between prostate cancer group and control group (p = 0.042). Percentage of null GST M1 gene was significantly higher in the cancer group (59.4 %) than control (45.5 %). However, the result revealed no significant association between the prostate cancer and IGF-2 or EGFR genotype distribution.
In part two, we screened the anti-tumor effects of FK228 (depsipeptide) on human prostate cancer. In NOD-SCID mice implanted with these cells, 50 mg/kg FK228 given orally thrice a week led to inhibition of tumor growth and metastasis, tumor regression in >25 % of animals and increased survival. Median time to the experimental end point (tumor volume 2 cm3 or death) in the untreated was 52 days, and average tumor volume was 0.8 ± 0.18 cm3. At the same time, 94.4 % of FK228-treated mice survived and had average tumor volumes of 0.37 ± 0.1 cm3. Sizeable metastases positively stained for PSA and limited air gaps were found in lungs of untreated mice. In animals treated with FK228, lung morphology appeared normal. Primary tumors of treated animals were highly positive for PSA and had an elevated level of p21 and the proapoptotic protein, Bax. Sections taken from FK228-treated animals, examined under an electron microscope, exhibited condensed chromatin and apoptotic bodies. PSA serum levels were higher in untreated compared to treated animals and correlated with tumor volume. Since prolonged oral administration with 50 mg/kg or a single oral dose of 1.2 g/kg FK228 did not cause adverse effects and the former exhibited significant anticancer activity.
In summarizes, this study suggests that the GST M1 gene may be associated with susceptibility of prostate cancer in the Taiwan population and FK228 is likely to display a high therapeutic index and may be beneficial for prostate cancer patients.

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