2018-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/694328摘要：在婦癌的領域中，卵巢癌逐漸成為一個愈來愈重要的疾病，根據衛生福利部國民健康署的癌症登記報告，卵巢癌的發生率逐年升高，且其死亡率在婦女的惡性腫瘤中名列第一。卵巢癌的預後因子包括腫瘤分期、病理組織型態、惡性化的程度、手術後的殘留腫瘤及對化學治療的反應和抗藥性。化療抗藥性在腫瘤復發與惡化扮演重要的角色，目前有關紫杉醇抗藥性的可能機制包括多重抗藥性基因的過度表現、微管蛋白發生變異、細胞凋亡途徑受抑制…等。鉑類藥物抗藥性的可能機制包括運輸蛋白的異常表現、增強的DNA 修復作用、細胞凋亡途徑受抑制…等。我們先前的研究發現，DOCK4 基因表現異常之卵巢癌患者具有較差的整體存活期。在這個研究計劃裡，我們將假設DOCK4 會調控藥物抗藥性的可能機制，來影響卵巢癌細胞的化療抗藥性，藉由卵巢癌細胞株與小鼠的實驗，進而探討DOCK4 在卵巢癌細胞的化療抗藥性機制中所扮演的角色，期望對未來卵巢癌治療提供新的策略。<br> Abstract: Ovarian cancer becomes a more and more important disease gradually in the field ofgynecologic malignancies. According to the reports of the cancer registration of the HealthPromotion Administration, Ministry of Health and Welfare, the incidence of ovarian cancerincreased in recent years and the mortality rate is highest in all gynecologic malignancies inTaiwan. The prognostic parameters for ovarian carcinomas include tumor stage, histologicalsubtype, degree of malignancy, residual tumor after surgical intervention and the response tochemotherapy. The drug resistance plays an important role in the tumor recurrence andprogression. The possible mechanisms of resistance to paclitaxel include the over expression ofmultiple drug resistance genes, alternation of the tubulins, inhibition of apoptosis pathway…etc.And the possible mechanisms of resistance to platinum include the abnormal expression oftransporter genes, enhanced DNA repair effects, inhibition of apoptosis pathway…etc.Our preliminary results in this year MOST-granted project (105-2314-B-002 -151) revealedthat aberrant DOCK4 expression was associated with poor prognosis in the patients of epithelialovarian carcinoma. In the current proposal, we hypothesize that DOCK4 will have an influence onchemo-resistance of ovarian cancer cells through the possible mechanisms of the drug resistance.We will figure out the underlying mechanisms of DOCK4 gene in drug resistance of ovariancarcinoma cells. It will provide new strategies for the managements of ovarian cancer patients.