2020-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/650417"1. 計畫中文摘要/Abstract in Chinese (maximum 500 characters) 卵巢高級漿液性癌是高度致死的婦科惡性腫瘤，主要是由於晚期診斷和化學耐藥性。減瘤手術和化學療法後治療復發腫瘤仍然是此惡性腫瘤的主要問題。癌症幹細胞（CSC）具有自我更新能力且有化學抗性，是治療惡性腫瘤的新面向。許多實驗發現CSC有高可塑性，且可以在幹細胞和非幹細胞狀態間可逆地轉化。此外，單個腫瘤內的CSC有不同的表現型。目前各種CSC的治療方法很多是針對腫瘤微環境的“幹細胞利基”。基於二維培養的體外研究缺乏腫瘤微環境中非腫瘤成分，沿續我們先前的球體培養模型的研究，我們計劃在3維細胞培養中包含更多非腫瘤元素，以便更廣泛地研究腫瘤微環境。此研究中，我們計劃建立一個模仿器官的3維培養系統，結合腫瘤相關的纖維母細胞（腫瘤微環境中的主要非腫瘤細胞）和間皮細胞（卵巢腫瘤擴散到骨盆腔時腫瘤微環境中的重要元素）。經化學治療藥劑篩選並驗證幹細胞標誌高表達量後，我們將利用從癌細胞和3維培養的條件培養液進行的微陣列研究中發現的因子來調節3維培養模型的腫瘤微環境。目標是找出腫瘤與腫瘤微環境相互作用中有關的因素，這些因素與卵巢癌的腫瘤幹細胞性和化學耐藥性有關，將可用於卵巢癌患者的復發追蹤和治療。" Ovarian high-grade serous carcinoma is a highly lethal gynecological malignancy, mainly due to late diagnosis, chemoresistance and tumor recurrence. Thus, treating recurrent tumors after debulking surgery and chemotherapy remains the main issue of this deadly malignancy which still remains to be improved. Cancer stem cells (CSCs) have become a new aspect in treating malignancies, since these cells have self-renewal ability and are chemoresistant. The evolving concept of CSCs suggests that CSCs have high plasticity and can reversibly transit between a stem cell and non-stem cell state; furthermore; CSCs from an individual tumor can exhibit different phenotypic states. Various approaches of therapeutic targeting CSCs have been attempted, mostly aiming at the “stem cell niche” of tumor microenvironment. Conventional in vitro 2D monolayer culture falls short of the non-tumor elements in the tumor microenvironment. In continuity with our previous study of in vitro sphere culture model enriching chemoresistant stem cells, we plan to include more elements in the in vitro 3D culture system for a wider view of the tumor microenvironment. In this study, we plan to set up a 3D culture system mimicking organotypic model incorporating tumor associated fibroblasts (the main non-tumor cells in the tumor microenvironment) and mesothelial cells (the important element in the tumor microenvironment when ovarian tumors spread to the pelvic cavity). After chemotherapeutic agent selection and verification of high expression level of stem cell markers, we will modulate the tumor microenvironments of 3D culture by key factors/regulators found from the microarray studies from the cancer cells and the conditioned medium collected from 3D culture. The ultimate goal is to identify factors/pathways involved in the interaction of tumor and tumor microenvironment, which are related to tumor stemness, chemoresistance and recurrence in ovarian carcinoma. These potential markers can be applied for serum testing during patient follow up and treatment of recurrent tumors.卵巢癌抗藥性癌症幹細胞腫瘤微環境3維模仿器官培養ovarian carcinomachemoresistancecancer stem cellstumor microenvironment3D organotypic culture