研究背景:胰腺癌（Pancreatic Cancer,PC）是一種高侵襲性、高致命性的惡性腫瘤,具有發(fā)病隱匿、缺乏特征性癥狀等特點(diǎn),這就決定了該病患者手術(shù)切除率低且術(shù)后死亡率高。目前,胰腺癌的臨床治療主要以抗代謝藥物（如5-氟尿嘧啶、吉西他濱和NAB紫杉醇等）治療和靶向藥物（如貝伐單抗、西妥昔單抗等）治療為主。在過(guò)去的十年中,盡管抗代謝治療和靶向治療得到了較好的發(fā)展,但由于胰腺癌表型的高侵襲性及其對(duì)化療藥物的耐藥性等,致使患者的生存率并無(wú)明顯的改善。因此,深入探究胰腺癌發(fā)生發(fā)展的分子機(jī)制、尋找更為有效的診斷和治療干預(yù)靶點(diǎn)對(duì)于改善胰腺癌患者的預(yù)后和生存質(zhì)量具有非常重要的意義。多聚腺苷酸結(jié)合蛋白相互作用蛋白 1（Polyadenylate-binding protein-interacting protein 1,PAIP1）是由PAIP1基因（位于5p12）編碼的含有479個(gè)氨基酸的磷酸腺苷結(jié)合蛋白。它可與EIF4A、EIF3結(jié)合刺激翻譯起始,參與調(diào)控細(xì)胞的生長(zhǎng)、增殖和分化。同時(shí),PAIP1也參與mRNA的穩(wěn)定--通過(guò)與主要蛋白編碼區(qū)的不穩(wěn)定性決定因子（MCRD）結(jié)合穩(wěn)定c-fos原癌基... 

【文章頁(yè)數(shù)】：120 頁(yè)

【學(xué)位級(jí)別】：博士

【文章目錄】：
中文摘要
ABSTRACT
ABBREVIATIONS
1. INTRODUCTION
    1.1 Pancreatic cancer and clinical treatment
    1.2 Poly(A)-binding protein-interacting protein 1
    1.3 AKT signaling pathway in tumor development
    1.4 Epithelial-mesenchymal transition and associated genes
        1.4.1 Epithelial-mesenchymal transition process
        1.4.2 Epithelial-mesenchymal transition markers
            1.4.2.1 EMT marker Vimentin and Snail 1/2
            1.4.2.2 EMT transcriptional factor ZEB 1/ZEB2
            1.4.2.3 EMT marekers Vimentin and E-cadherin
    1.5 Angiogenesis and tumor progression
    1.6 Study design
2. MATERIALS AND METHODS
    2.1 Materials
        2.1.1 Experimental reagents and instruments
    2.2 Methods
        2.2.1 Ethic statement
        2.2.2 Clinical specimens
        2.2.3 Cell culture
        2.2.4 Transfection
        2.2.5 Stable cell line generation
        2.2.6 TCGA BC cohorts
        2.2.7 Cell viability assay
        2.2.8 Colony-forming assay
        2.2.9 Wound healing assay
        2.2.10 Migration assay
        2.2.11 Invasion assay
        2.2.12 Vasculogenic mimicry analysis
        2.2.13 Matrigel tube formation assay
        2.2.14 Chick chorioallantoic membrane assay (CAM assay)
        2.2.15 Immunofluorescence
        2.2.16 Western blot
        2.2.17 Immunohistochemistry
        2.2.18 In vivo tumorigenesis and metastasis assays
        2.2.19 Statistical analysis
3. RESULTS
    3.1 PAIP1 is highly expressed in human PC
    3.2 PAIP1 is correlated with poor prognosis in human PC
    3.3 PAIP1 signficantly promoted the proliferation and colony formation of PC cells
    3.4 PAIP1 promotes the migration, invasion and EMT progression of PC cells
    3.5 PAIP1 promotes angiogenesis in PC cell lines
    3.6 PAIP1 augments PC angiogenesis and invasion potential via AKT pathway activation
    3.7 The overexpression of PAIP 1 promotes tumors growth and metastasis in tumor xenografts
4. DISCUSSION
5. CONCLUSIONS
REFERENCES
攻讀博士學(xué)位期間取得的科研業(yè)績(jī)
致謝



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