本文選題：宮頸癌 + 放療敏感性��； 參考：《復(fù)旦大學(xué)》2014年博士論文

【摘要】：目的：1.eIF-4A1、eIF-4E、eIF-4G1在宮頸癌的表達(dá)及臨床意義；2.調(diào)控eIF-4A1表達(dá)對宮頸癌Siha、Hela細(xì)胞功能的影響；3.eIF-4A1對宮頸癌放療敏感性的影響及機(jī)制。材料和方法：35例正常宮頸組織及137例宮頸癌患者的石蠟標(biāo)本均來源于復(fù)旦大學(xué)附屬腫瘤醫(yī)院組織庫。采用Siha、Hela細(xì)胞做為載體進(jìn)行體外體內(nèi)實驗。實驗方法包括CCK8試劑盒檢測細(xì)胞增殖實驗,Transwell檢測細(xì)胞的遷移侵襲能力,流式細(xì)胞儀檢測細(xì)胞凋亡和周期,克隆形成實驗檢測細(xì)胞的放療敏感性,以及裸鼠皮下成瘤和放療相關(guān)實驗。Western blot實驗進(jìn)行相關(guān)的機(jī)制研究。結(jié)果：1.eIF-4A1、eIF-4E 和 eIF-4G1在正常宮頸組織中表達(dá)陰性,宮頸癌中高表達(dá)(陽性率大于80%)。eIF-4A1、eIF-4 E 和 eIF-4G1表達(dá)水平與患者的FIGO分期、組織病理學(xué)類型、盆腔淋巴結(jié)有無轉(zhuǎn)移相關(guān)(P0.05)。放療后eIF-4A1和eIF-4E表達(dá)變化和患者的放療敏感性相關(guān)(P分別為0.029、0.012)。放療后eIF-4A1表達(dá)降低的患者預(yù)后較好(P=0.002),并且是患者良好預(yù)后的獨立影響因素(P=0.047)。2.抑制eIF-4A1表達(dá)可以抑制宮頸癌細(xì)胞的增殖、侵襲轉(zhuǎn)移,促進(jìn)細(xì)胞凋亡,延遲細(xì)胞放療所致DSB損傷修復(fù)。3.體內(nèi)體外實驗證實,降低eIF-4A1表達(dá)可以增加宮頸癌的放療敏感性。結(jié)論：放療后eIF-4A1表達(dá)下降是宮頸癌良好預(yù)后的獨立影響因素。eIF-4A1通過延遲放療后DSB損傷修復(fù)增加宮頸癌的放療敏感性。
[Abstract]:Objective to investigate the expression and clinical significance of eIF-4A1EIF-4EIF-4G1 in cervical carcinoma. Regulation of eIF-4A1 expression on the function of Siha-Hela cells in Cervical Cancer. 3. The effect of eIF-4A1 on the radiosensitivity of cervical cancer and its mechanism. Materials and methods paraffin specimens of 35 normal cervical tissues and 137 cervical cancer patients were collected from the tissue bank of tumor Hospital affiliated to Fudan University. Sihagne Hela cells were used as carriers for in vitro experiments. The methods included CCK8 kit and Transwell assay, flow cytometry to detect cell apoptosis and cell cycle, clone formation assay to detect the sensitivity of cell to radiotherapy, to detect cell migration and invasion ability, to detect cell apoptosis and cell cycle by flow cytometry. The mechanism of subcutaneous tumorigenesis and radiotherapy-related experiments in nude mice was studied by Western blot assay. Results 1. The expression of eIF-4A1eIF-4E and eIF-4G1 were negative in normal cervix, and the overexpression of eIF-4A1eIF-4E and eIF-4G1 in cervical carcinoma were correlated with Figo stage, histopathological type and pelvic lymph node metastasis (P0.05). The changes of eIF-4A1 and eIF-4E expression were correlated with the radiosensitivity of patients after radiotherapy (P = 0.029, 0.012, respectively). The patients with lower expression of eIF-4A1 after radiotherapy had a better prognosis (P0. 002) and were independent factors of good prognosis (P0. 047). 2. Inhibiting the expression of eIF-4A1 can inhibit the proliferation, invasion and metastasis of cervical cancer cells, promote apoptosis and delay the repair of DSB damage induced by radiotherapy. In vivo and in vitro experiments have shown that reducing the expression of eIF-4A1 can increase the radiosensitivity of cervical cancer. Conclusion: the decrease of eIF-4A1 expression after radiotherapy is an independent factor influencing the good prognosis of cervical cancer. EIF-4A1 increases the radiosensitivity of cervical cancer through DSB damage repair after delayed radiotherapy.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R737.33

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本文編號：2096352