研究影響
按照《實驗室》的研究方向，我們的研究人員致力於新領域中開發有系統的原創科研項目。這些創新的研究成果為肝病研究帶來重要發現，也為開發更好更有效的治療方法帶來希望:
肝癌幹細胞的鑑定和識別
肝癌(肝細胞癌 hepatocellular carcinoma)是一種位居世界第五大癌症之列的複雜疾病。癌症生物學領域有新觀點認為癌症是受一小部分的細胞群體所驅動，這類細胞群體被稱為“癌症幹細胞 (cancer stem cells, CSCs)”，或者“腫瘤起始細胞 (tumor-initiating cells (TICs))”。 CSCs具有自我複製能力，能夠引發腫瘤在體內生成，並且對化療有抗藥性。
《實驗室》在破解肝癌幹細胞的奧秘方面是領先的科研團隊。我們對幹細胞標記物CD133進行了研究，研究成果展示了肝癌幹細胞在調控腫瘤生成過程中的幾條重要的信號通路，也凸顯出CD133 (+)是一個潛在的治療標靶。[1-5] 《實驗室》並且首次鑑定出一個新的肝癌幹細胞亞群CD24(+)，可針對肝癌的藥物抗性、轉移和腫瘤復發。 [6]
我們的研究結果顯示以CD47為治療標靶是對肝細胞癌患者有吸引力的治療方案。[7, 8] 並且發現了關於肝癌幹細胞調控及建立阻斷肝癌幹細胞功能的選擇性目標的新知識。
肝癌轉移的分子機制
肝癌是一種常見的癌症，因其轉移性高而導致極高的死亡率，同時轉移也是導致腫瘤復發和器官衰竭的主因。了解細胞信號通路及癌症轉移對開發新的肝癌治療方案至關重要。
《實驗室》在探討肝癌轉移機制和鑑定重點信號通路方面成績斐然。肝癌缺失基因DLC1(Deleted in Liver Cancer 1)/RhoE/microRNA miR-139信號通路在肝癌轉移中有重要抑制作用。《實驗室》對於該通路的探索和研究一直處於領先地位，我們的研究對了解肝癌轉移的分子機制有重要的貢獻。[9 – 12]
《實驗室》另一項創新研究的突破性成果是發現抗氧化劑促進腫瘤發生和生長，以抗氧化通路為治療標靶來抑制腫瘤生長是肝癌研究的突破發現。[13]
肝癌基因組學和表觀遺傳
肝癌的發生是由基因水平和表觀遺傳水平的積累遺傳改變驅動的一個多步驟過程。《實驗室》致力於闡述人類肝細胞癌所涉及的表觀遺傳。我們對表觀遺傳調控的分子機理進行了詳盡研究，並取得了優異成果。
RNA編輯是指在RNA序列的轉錄後改變遺傳信息，是一個附加的表觀遺傳調控機制。人類最常見的RNA編輯類型是腺嘌呤核苷轉次黃嘌呤核苷 (adenosine(A) →inosine (I)) 。我們的研究確定了AZIN1的A→I RNA編輯與引至肝癌的密切關係。總括來說，AZIN1的A→I RNA編輯可能是人類肝癌發病的潛在驅動力。[14]
《實驗室》的科研團隊對染色質重塑蛋白CHD1L (Chromodomain Helicase DNA Binding Protein 1 Like)展開了各項研究。我們的科研成果揭示了標靶CHD1L極具治療潛力和預後價值，突顯了CHD1L在肝癌發生過程中的重要的臨床和功能意義。 [15 - 17]
組蛋白修飾酶失調是人類肝細胞癌中的常見現象。 《實驗室》對不同的組蛋白甲基轉移酶(SUV39H1(Suppressor of variegation 3-9 homolog 1)，EHZ2(Enhance of Zeste)，SETDB1 (SET domain, bifurcated 1)) 在肝癌發生的分子機制進行深入探討，全面闡明肝癌發生的機制。 [18 – 20]
乙型肝炎生物學和治療
《實驗室》擁有頂尖科學家致力於開發針對慢性乙型肝炎(HBV)的抗病毒療法。科研重心主要集中在長期抗病毒療法的開發和監測，鑑定隱匿性乙型肝炎感染(occult HBV infection, OBI)，在乙型肝炎之再活化及在肝細胞癌發展中的重要作用。
《實驗室》是為慢性乙型肝炎病人進行定量檢測共價閉環DNA (covalently closed circular DNA, cccDNA)的領先團隊。我們的研究發現長期抗病毒療法有引致cccDNA含量增加的可能性，並引發針對該可能性的進一步探討和鑑定。 [22, 23]
隱匿性乙型肝炎感染(OBI)在接受免疫抑制療法的病人中是一個威脅生命的重要議題。《實驗室》是研究OBI的先驅。我們的科研成果表明OBI為監控乙型肝炎標記物，為預防乙型肝炎再活化及製定治療策略提供了至關重要的證據。 [24 – 28] .
肝癌臨床管理與治療
肝癌(肝細胞癌)是世界第五大癌症，在中國發病率極高。肝細胞癌的癌症分期有別於其他癌症的分期，其中重要原因是原有的肝病(如慢性肝炎，肝硬化等)能對肝細胞癌患者預後產生極大影響。
《實驗室》團隊開發了亞洲首個肝癌分期系統:香港肝癌分期系統(Hong Kong Liver Cancer Staging System, HKLC)。該項原創突破性成果獲得了國際認可，並能夠提供更好的預後分類及治療指徵。[29]
肝切除術是肝癌手術治療的基石。然而並非每一位病人都適用於此療法。過去數十年，高能聚焦超聲消融術(high-intensity focused ultrasound , HIFU) 成為局部消融治療的新形式。針對病人接受HIFU療效的評估，《實驗室》展開了各項研究，為不適宜做切除手術的而接受HIFU治療的肝癌病人，提供了寶貴的經驗指導。 [30 - 32]
參考資料
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