流行病學研究指出,臺灣地區口腔黏膜下纖維化症及口腔癌發生率與嚼食檳 榔有密切關係。根據衛生署癌症登記報告指出,口腔癌在臺灣男性十大癌症中死 亡率與發生率皆位居第四位,口腔癌年增率也是臺灣地區年增率最高之癌症。其 特性為容易復發及轉移,五年內存活率極低,因此尋找新穎生物標誌及有效療法 將提供臨床很大的幫助。近年來奈米技術在生醫材料上的應用已經有一定的進 展,目前已經有較好研究基礎平台的便是奈米藥物傳輸載體。此種技術是將藥物 或是其他生物分子包覆在奈米載體中,並同時在載體表面修飾特異性的標靶分 子,通過這樣的技術來提高與細胞表面特異性受體的結合,藉由此方法讓細胞更 容易辨識藥物載體,並加以控制適當的藥物釋放速度、高度的吸收率以增進治療 效果。總計劃及子計畫為針對台灣本土特有的嚼食檳榔文化引起口腔黏膜下纖維 化症及口腔癌之相關研究,且配合本校中長程發展特色及國健局進行口腔黏膜疾 病篩檢之政策。為了達到這個目標,我們籌組了這個整合型轉譯醫學計畫,結合 了臨床醫師、口腔病理醫師及基礎研究人員,擬以四個子計劃進行以下的研究:(一) 口腔黏膜下纖維化症之造纖維母細胞與口腔癌細胞交互作用之分子機轉探討;(二) 天然化合物在口腔癌抗轉移與誘導凋亡效果的開發及其作用機轉之探討;(三)標靶 口腔癌幹細胞特性之研究: 幹源標誌臨床意義、反轉化療放療抗性、與治療標的之 研發;(四) 5-胺基酮戊酸 (ALA) 奈米化光動力療法於口腔癌前病變及口腔癌治療 應用性及其作用機轉之探討。希望藉由此一整合性計畫的進行,能開發出新的生 物標誌因子,以應用於口腔黏膜下纖維化症、口腔癌的診斷與監測,及利用奈米 生醫材料應用開發口腔癌標靶治療藥物,提供未來個人化醫療之應用。 Oral submucous fibrosis (OSF) is a chronic progressive scarring disease which has been considered as pre-cancerous condition of oral mucosa. In Taiwan, there are two million people who have the areca quid chewing habit, which has been suspected to elevate the incidence of oral premalignant lesions; about 80% of all oral cancer deaths are associated with this habit. Because of the higher incidence rate of oral cancer in Taiwan, to investigate the carcinogenesis of oral cancer is urgent and the molecular mechanisms will provide useful knowledge in prevention, diagnosis, and therapy. To reach the goal, an integrated project is organized with four sub-projects that coordinates collaboration among basic researchers, clinicians, pathologists to investigate (1) Molecular mechanisms of the interplay between oral submucous fibrosis-derived fibroblasts and oral cancer. (2) The study of natural compounds discovery and anti-oral cancer effect on metastasis and apoptosis. (3) Research on targeting cancer stem cells: clinical significance of stemness signature, reversal chemoradio-resistance, and therapeutic targets development. (4) Therapy application and molecular mechanisms of photodynamic therapy with 5-aminolevulinic acid (ALA)-based nanoparticle for oral pre-cancer lesions and oral cancer.