轉移，即細胞從原發腫瘤向遠端器官的擴散及其隨後的生長。儘管多年的研究在腫瘤的診斷、治療已有了長足進展，但是腫瘤轉移仍然是大多數腫瘤患者的死亡原因。
oct3/4(也稱Oct-3或Oct3/4) 屬POU轉錄因子一員， 最初鑒定為DNA結合蛋白，可活化基因轉錄。oct3/4表現在全能胚胎幹細胞(ES)和生殖細胞，維持幹細胞的自我更新與全能性或多能性。最近研究發現，oct3/4在許多癌症細胞中再度表現，目前已被用來作為偵測睪丸癌的指標。另有研究指出oct3/4 參與腫瘤的生成與轉移。我們發現oct3/4在小鼠膀胱癌細胞中再度表現，且在小鼠轉移性膀胱癌細胞MBT-2 lungmeta7 的表現量高於非轉移性膀胱癌細胞MBT-2。因此我們利用oct3/4 response element (oct4RE) 調控CMVm啟動子，並且建構一oct4RE調控CMVm的啟動子所驅動的溶瘤腺病毒(Ad.9OC)，達到對轉移性腫瘤細胞的專一毒殺作用。我們研究發現在oct3/4表現量比較高的轉移性膀胱癌細胞MBT-2 lungmeta7，oct3/4 response element (oct4RE) 調控啟動子的活性高於oct3/4表現量比較低的膀胱癌細胞MBT-2。同樣的，Ad.9OC在轉移性膀胱癌細胞產生的毒殺作用的能力也優於非轉移性膀胱癌細胞。而在動物實驗中，我們發現Ad.9OC 對於轉移性膀胱癌能更有效的抑制腫瘤的生長以及延長老鼠生存時間。由結果顯示，我們利用9Xoct4RE-CMVm 啟動子驅動的溶瘤腺病毒確實可有效治療轉移性膀胱癌腫瘤並且提高溶瘤腺病毒對轉移性膀胱癌的選擇性。

Current treatment options for metastatic tumors lack efficacy and metastases targeting remains a major challenge for curing cancer. The POU homeodomain protein Oct-3/4 (where Oct stands for octamer binding protein) is an embryonic transcription factor expressed in germ cells and embryonic stem but not expressed in normal somatic tissues. It has been shown recently that embryonic genes are re-expressed in many cancer cells. Generally, cancer cells are immortal, undifferentiated and invasive. Therefore, it might be expected that cancer cells express genes in common with early embryonic cells. Bladder cancer is a common human malignancy and is the second most common genitourinary malignancy. Patients with metastatic disease have poor long-term survival rates despite systemic multiagent chemotherapy. Thus, the re-expression of the embryonic gene Oct-3/4 in cancer cells may have a high potential for cancer therapy. In our study, Oct-3/4 expression was found to be higher in metastatic bladder cancer cells than in non-metastatic bladder cancer cell lines. Therefore, we have exploited 9 copies of Oct-3/4 response elements ligated to CMVmini (CMVm) promoter to investigate its transcription activity in metastatic bladder cancer. The transcription activity of the Oct4RE-CMVmini promoter was higher in metastatic than in non-metastatic bladder cancer cells. We also determined whether oncolytic adenovirus carrying 9 copies of Oct-3/4 response elements (Ad-9OC) replicated more selectively in metastatic bladder cancer. Our results showed that Ad-9OC exhibited higher oncolytic activity in metastatic bladder cancer than non-metastatic bladder cancer. Furethermore, Ad.9OC had better antitumor effects on tumor growth and survival in metastatic bladder cancer than in non-metastatic bladder cancer animal model. Taken together, these results suggest that Ad.9OC, a 9x Oct4RE-CMVm-driven oncolytic adenovirus, may have therapeutic potential for Oct-3/4 re-expressed bladder metastatic bladder cancer.

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