2014-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/651264摘要：原發性食道癌主要包含食道鱗狀上皮細胞癌(ESCC)與腺細胞癌，其中有 95 % 的食道癌是 ESCC。在缺乏標靶治療的情況下，食道癌預後極不佳，五年存活率平均不到 20 %。先前針對受體酪胺酸激酶(receptor tyrosine kinases，RTKs)與預後的關係，已發展出多種癌症標靶療法。Axl RTK 被發現與食道腺細胞癌的預後有關，並且被認為具有發展標靶治療的潛力。然而Axl與 ESCC的關係未曾被探討。我們先前以免疫組織染色法(IHC)分析 57 個 ESCC 組織，初步發現 Axl 的表現程度和 ESCC 的預後有顯著相關。我們並且也發現 Axl 與另一重要的 RTK，Her-2，在 ESCC 細胞中可能有交互作用。在本計畫中，我們欲以較大的檢體量與細胞模型，系統性地分析 Axl 在 ESCC 預後、藥物反應、與癌化之角色。 本兩年計畫的主要研究目標: 1) 於 300 對 ESCC 病患術中切除之非癌化與癌化組織中偵測 Axl、磷酸化 Axl, 其受體 Gas 6 與 Her-2 之表現量。 2) 分析上述 300 例 ESCC 組織中 Axl、磷酸化 Axl、Gas 6 與 Her-2 之表現量與病患存活、治療反應，與癌化程度的相關性。 3) 分析 Axl、磷酸化 Axl、Gas 6 與 Her-2 對於 ESCC 預後的影響是否有交互作用。 4) 於 ESCC 細胞與具有 Her-2 藥物抗性之 ESCC 細胞中，觀察 Axl 的抑制劑是否可以促進細胞死亡與對化學或物理治療的反應。 我們相信本研究將會為ESCC的標靶治療的方向提供珍貴的訊息，以改善此疾病之不良預後。<br> Abstract: Primary esophageal cancer presents most often as esophageal squamous cell carcinoma (ESCC) or adenocarcinoma. ESCC is the major cell type of primary esophageal cancer accounting for 95 % of the disease worldwide. Without efficient targeted drugs, the prognosis of esophageal cancer is relatively poor with a 5-year survival less than 20% in patients. Many targeted drugs for cancer have been developed based on the studies focusing on the prognostic relevance of receptor tyrosine kinases (RTKs) and their growth factor ligands. The Axl receptor tyrosine kinase has been suggested as a prognostic factor and a therapeutic target in esophageal adenocarcinoma. Whether Axl play some role in the prognosis of ESCC is unknown. We preliminary observed Axl expression in ESCC tissues associated with the prognosis of patients in 57 patients by immunnohistochemisty (IHC). We also demonstrated the possible functional interplay of Axl and Her-2 in ESCC. In current 2-year project, we intend to systematically investigate the roles of Axl in the prognosis, treatment response and carcinogenesis of ESCC with large sizes of clinical samples and in ESCC cells. The specific aims in the 2 years to come are: 1) To detected the expression of Axl, phospho-Axl, its major ligand Gas 6, and Her-2 by IHC and western blotting in both the tumor and non-tumor parts of 300 sets of esophageal tissues from ESCC patients. 2) To correlate the expression levels of Axl, phospho-Axl, Gas 6, and Her-2 with the clinical outcome and treatment responses of patients in the 300 patients with ESCC. 3) To analyze the cumulative effects of Axl, Gas 6 and Her-2 on the prognosis of patients with ESCC. 4) To investigate whether the inhibitors of Axl promote cell death or the responses to chemotherapy and radiotherapy in ESCC cells and Her-2 drug resistant ESCC cells. We believe this study will provide valuable direction and information of targeted therapy of ESCC and thus improve clinical outcome of the deadly disease.食道鱗狀上皮細胞癌Axl 受體酪胺酸激酶Her-2 受體酪胺酸激酶Gas 6 配體Esophageal squamous cell carcinoma (ESCC)Axlreceptor tyrosine kinase (RTKs)Her-2Gas 6