肝癌目前是台灣人民排名第二名容易發生的癌症，僅次於肺癌，同時致死率也是位居前十名，肝癌病患經過手術切除、放射性或是化療藥物治療後，相較於其他癌症，仍然有高復發率。復發的原因有許多種，但其中最令人頭疼的原因為癌幹細胞，此種類幹細胞在癌細胞族群中佔的比例極少，癌幹細胞是從一般幹細胞突變而來，因此它具有一般幹細胞的特性像是自我更新以及分化的能力，在經過治療後形成的微環境，會促使癌幹細胞的分化，進而形成腫瘤，在肝癌中的癌幹細胞主要來源有本身的肝幹細胞以及來自於骨髓的幹細胞。然而，癌幹細胞對於部分的化療藥物是具有抗藥性的，因此在進行化療治療後，並無法完全去除癌幹細胞，導致癌症復發。在過去的研究中發現，在小鼠體內登革病毒可以感染具有豐富造血幹細胞的骨髓，因此，我們假設癌幹細胞與造血幹細胞有類似的特性，或許登革病毒也有能力感染癌幹細胞，對癌幹細胞造成影響。在本篇研究我們拿取肝癌病人的腫瘤組織和非腫瘤組織進行登革病毒感染。首先，我們發現腫瘤細胞較容易受登革病毒感染，能有效的產出高於非腫瘤細胞大約10-100倍的病毒量，接著我們使用同時表現於造血幹細胞及癌幹細胞的幹細胞標誌(CD133, CD34, CD117)與腫瘤細胞產生的病毒量進行分析，發現腫瘤細胞產生的登革病毒量與幹細胞族群有顯著的正相關，而非細胞族群則是負相關，並且發現帶有CD133標誌的細胞在腫瘤細胞族群較非腫瘤細胞族群多，接著我們將帶有CD133標誌的腫瘤細胞分離出並進行登革病毒感染，研究結果顯示在腫瘤細胞中帶有CD133標誌的細胞確實可被登革病毒感染，進一步與總腫瘤細胞族群產生的登革病毒分析發現，CD133細胞是登革病毒在肝癌第一個感染並產生病毒的目標細胞。綜合上述實驗，我們發現在肝癌腫瘤細胞中，登革病毒確實可以感染帶有CD133標誌的幹細胞，這項發現可以再延伸探討受登革病毒感染對於此幹細胞的致瘤性影響，或許，在未來可以透過登革病毒並用於治療肝癌癌幹細胞，藉此降低復發機率。

Hepatocellular carcinoma (HCC) is one of the top ten lethal cancers in Taiwan. It is easy to relapse after HCC patients were treated. Cancerous recurrence is related to cancer stem cells (CSCs). CSCs are minor populations which present the characteristics of stem/ progenitor cells such as self-renewal and differentiation abilities in tumor. CSCs in HCC are originally from hepatic stem cell and bone marrow stem cells. In previous studies, the hematopoietic progenitor cells of bone marrow are important for dengue virus (DENV) infection. We hypothesize that CSCs of HCC can be infected by DENV if they have similar property with hematopoietic progenitor cells. The non-tumor and tumor tissues of HCC patients were used in this research after signing informed consent. Cells were extracted from these tissues prior to DENV study. Results showed that the cells from tumor tissues were highly permissive to DENV infection and produced approximately 10-100 folds higher viral titer than cells from the non-tumor appearance tissues. Both cells from the tumorous and non-tumor tissues were analyzed by flow cytometry.to determine the stem cell populations Results showed that cells populations containing CD133+ and/or CD117+ and/or CD34+ stem cell markers were positively correlation with viral titers while the negative subsets demonstrated to be negative correlation. FACS results revealed that CD133+ cells appeared to be much more in tumor tissues compared to the non-tumor tissues. Furthermore, CD133+ cells sorted out from tumor tissues by magnetic beads were highly permissive to DENV infection. Our tabulated results suggested that the CD133+ stem cells are likely the initial target for dengue virus infection in HCC. We will investigate the effect of DENV infection on HCC CD133 target cells, particularly on the tumorigenicity of the cell after DENV infection. If DENV can infect CSCs in HCC to affect their tumorigenicity, this become a possible candidate for anti-cancer treatment of HCC disease.

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