血管新生是從已存在的血管生長出新血管的過程，在正常的組織生長過程以及許多的致病機轉，它都扮演了很重要的角色，惡性腫瘤的生長，也必須經由新生血管來供應養分及氧氣，它也提供了腫瘤向外侵犯及轉移的管道。因此，利用抑制血管新生是一種治療癌症的方法。血管靜止蛋白是一種血管新生抑制物，它是血纖維蛋白溶酶原的內部片段，帶有前四個kringle domains，在我們實驗室之前的研究發現三個血纖維蛋白溶酶原片段K320-351(K3333), K420-436(K4418), 和K420-448(K4430)是具有潛力的血管新生抑制物，它們比K420-461 (K1-4) (angiostatin)更能夠抑制內皮細胞的增生及移動。為了要探討這些片段對腫瘤生長的影響，所以將這些不同的片段構築在反轉錄病毒載體中並用以處理動物，從實驗中發現到帶有K4418 反轉錄病毒載體抑制腫瘤生長的能力較其它片段好，除此之外，接受K4418 和K1-4反轉錄病毒载體治療的小鼠腫瘤，血管密度也較低。為了加強抗癌效果，我們增加K4418 反轉錄病毒載體劑量，結果顯示連續打入七劑的平均腫瘤體積小於不作處理或打入三劑的組別。另外也評估是否在早期打入反轉錄病毒載體會有更好的效果，為了這目的，帶有K4418 反轉錄病毒載體在腫瘤細胞植入老鼠後隔天打入，每兩天一劑共五劑，從結果中發現在早期治療(腫瘤細胞植入老鼠後隔天打入)的腫瘤體積小於晚期治療的組別(在腫瘤細胞植入老鼠後五到七天治療)。腺衛星病毒是個有效率且可長期表現基因的載體，已被廣泛的使用在多種動物模式及人類臨床試驗，所以我們使用帶有K4418的腺衛星病毒載體做治療，結果打入K4418的腺衛星病毒載體也能夠有效的抑制黑色素瘤的生長。近年來，因為已經有許多報導指出利用合併各種療法可以得到更好的療效，而且我們之前的研究顯示rSPE B (Streptoccal Pyrogenic Exotoxin B)能夠誘發B16F10細胞(小鼠黑色素瘤細胞)產生細胞凋亡的現象，所以我們也想了解結合K4418 反轉錄病毒載體和rSPE B的治療成效如何，從實驗結果中發現合併治療效果的確比單一種治療好。總結來說，K4418治療黑色素瘤的效果確實比K1-4(angiostatin)好，利用合併抑制血管新生和使細胞凋亡藥物的療法也的確可以增加療效。

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