發(fā)布時(shí)間：2020-12-26 17:00

　　簡介背景:急性淋巴細(xì)胞白血病是青少年中最常見的血液系統(tǒng)惡性腫瘤,成人也可發(fā)病。耐藥是急性淋巴細(xì)胞白血病治療失敗的重要原因,臨床上迫切需要開發(fā)新的治療方法或靶向治療藥物。FKBP51是親免素蛋白家族成員,在淋巴細(xì)胞生理性表達(dá)。FKBP51參與維持細(xì)胞生長、細(xì)胞惡變以及化療耐藥。目的:利用Jurkat細(xì)胞系,研究FKBP51蛋白對(duì)急性淋巴細(xì)胞白血病細(xì)胞生長和化療藥物敏感性的影響。探討FKBP51作為急性淋巴細(xì)胞白血病發(fā)展/演化和對(duì)抗癌藥物耐藥的生物學(xué)標(biāo)志的可能性。方法:用慢病毒載體包裝FKBP51,感染Jurkat細(xì)胞,建立過表達(dá)FKBP51的Jurkat細(xì)胞系,用shRNA-FKBP51質(zhì)粒轉(zhuǎn)染Jurkat細(xì)胞,建立敲除FKBP51的Jurkat細(xì)胞系。western blot檢測FKBP51蛋白表達(dá)水平,驗(yàn)證細(xì)胞建系成功。經(jīng)CCK-8分析檢測細(xì)胞增殖,Muse（?）細(xì)胞分析儀檢測細(xì)胞周期分布,western blot研究絲氨酸/蘇氨酸蛋白激酶（AKT）和核因子κB（NF-κB）信號(hào)通路。統(tǒng)計(jì)學(xué)處理:應(yīng)用SPSS 25.0和Graph Pad Prism 6統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)分析,實(shí)驗(yàn)數(shù)據(jù)... 

【文章來源】：山東大學(xué)山東省 211工程院校 985工程院校 教育部直屬院校

【文章頁數(shù)】：120 頁

【學(xué)位級(jí)別】：博士

【文章目錄】：
Abstract
中文摘要
附錄
Thesis framework
Chapter One:General Introduction
    1.1 Statement
    1.2 Hypothesis
    1.3 Aim
    1.4 Obectives
Chapter Two:Literature Review
    2.1 Hematopoiesis
    2.2 Cytokines
        2.2.1 Functional classification
        2.2.2 Role of Endogenous Cytokines in Health and Disease
        2.2.3 Application of Therapeutic drugs
    2.3 Cancer
        2.3.1 History of Cancer
        2.3.2 The hallmarks of Cancer
    2.4 Leukemia
        2.4.1 Acute lymphoblastic leukemia
            2.4.1.1 Epidemiology
            2.4.1.2 Risk Factors
            2.4.1.3 Pathogenesis
            2.4.1.4 Classification of Acute lymphoblastic leukemia
    2.5 Philadelphia chromosome （Ph）
        2.5.1 Leukemogenesis-How?
        2.5.2 Breakpoints of translocation t （9;22） BCR-ABL translocation
    2.6 FK506 binding protein 51
        2.6.1 Functions of the FKBP51
        2.6.2 Clinical Significance
            2.6.2.1 Expression of FK506 binding protein51 in Cancer
    2.7 A serine /threonine- protein kinase
        2.7.1 Pathophysiology of AKT
        2.7.2 AKT and FKBP51
    2.8. Nuclear factor kappa- light-chain- enhancer of activated B cell
        2.8.1 NF-κB signaling pathways
        2.8.2 NF-κB and FKBP51
    2.9 Chemotherapy
        2.9.1 Treatment of Chemotherapy is divers from other theray
        2.9.2 Cell cycle phases
    2.10 Dexamethasone
    2.11 Lipopolysaccharide
    2.12 Tumor necrosis factor-alpha Tumor necrosis factor-alpha
        2.12.1 Role of TNF-α
    2.13 Jurkat Cell line
    2.14 Lentiviiral Vectors
        2.14.1 Factors Influencing the Infectivity of Lentiviral Vectors
Chapter Three: Materials and methods
    3.1 Materials
        3.1.1 Cell Cultures and treatments
    3.2 Common related materials
    3.3 Cell Cultures
        3.3.1 Principle
        3.3.2 Method
        3.3.3 Multiplicity of Infection （MOI）
    3.4 RNA Isolation and Real-Time Quantitative RT-PCR
        3.4.1 Principle
        3.4.2 Method
    3.5 Cell proliferation assay
        3.5.1 Principle
        3.5.2 Method
    3.6 Cell Cycle assay
        3.6.1 Principle
        3.6.2 Method
    3.7 Western blot assay
        3.7.1 Principle
        3.7.2 Method
    3.8 FKBP51-shRNA （Knockdown）
        3.8.1 Principle
        3.8.2 Method
    3.9 FKBP51 Regulated AKT Pathway
        3.9.1 Principle
        3.9.2 Method
    3.10 NF-κB Signaling pathway
        3.10.1 Principle
        3.10.2 Method
    3.11 Chemosensitivity Assay
        3.11.1 Principle
        3.11.2 Method
    3.12 Statistical analysis
Chapter Four- Results
    4.1 The Efficiency of Infection
    4.2 Overexpression of FKBP51 in ALL Cell lines
        4.2.1 Western blotting
        4.2.2 Cell proliferation/viability assay
    4.3 The shRNA- FKBP51 （Knockdown）
    4.4 The role of FKBP51 in AKT Signaling Pathway
    4.5 Western bloting analysis of FKBP51 overexpression and NF-κB kinaseactivity
    4.6 Western bloting analysis of shRNA-FKBP51 and NF-κB kinase activity
    4.7 CCK-8 assay, negative control and transfected Jurkat cell lines
Chapter Five: Discussion
Chapter Six: Conclusion and future perspective
    6.1 Conclusion
    6.2 Future perspective
Chapter Seven:References
Thesis Part Two Effect of Helicobacter pylori Infection on Hematological Parameters in KostiSudan
    附錄
    Chapter One: Intoduction
        1.1 Statement
        1.2 Hypothesis
        1.3 Obiective
        1.4 Rationale
    Chapter Two:Literature review
        2.1 Helicobacter pylori infection
            2.1.1 Prevalence of Helicobacter pylori infection
            2.1.2. Causes of H. pylori
            2.1.3 Pathophysiology
        2.2. H. pylori and Iron Deficiency Anemia
        2.3 Lactoferrin
        2.4 H. pylori and Megaloblastic Anemia
12 deficiency">            2.4.1 Causes of vitamin B₁₂ deficiency
        2.5 Pernicious anemia
            2.5.1 Schilling test
        2.6 Gastrointestinal Tract Endoscopy
        2.7 H.pylori and CagA
        2.8 H.pylori and signaling pathways
        2.9 Tumor suppressor p53
        2.10 Wnt signaling pathways
        2.11 H. pylori and obesity
        2.12 Diagnostic Methods of H. Pylori
    Chapter Three: Materials and Methods
        3.1 Study population and design
        3.2 Inclusion and Exclusion criteria
        3.3 Sampling procedure
        3.4 Estimation of hematological parameters
            3.4.1 Principle
            3.4.2 Method
        3.5 Reticulocytes （Retic） Count
            3.5.1 Principle
            3.5.2 Method
            3.5.3. Interpretation of the results
                3.5.3.1 Normal account
                3.5.3.2 Decreased reticulocyte count
                3.5.3.4 Increased reticulocyte count
        3.6 H. pylori screening
        3.7 Statistical analysis
        3.8. Ethical statement
    Chapter Four: Results
        4.1 Comparison of Demographic and Hematological Parameters between Patientsand Control Groups
        4.2 Evaluations of Hematological Parameters between Patients, Control groupsand their correlation with H.pylori
        4.3 Platelet count between control and patients'groups
        4.4 Morphological examination of reticulocyte count
        4.5 Morphological blood picture
    Chapter Five:Discssion
    Chapter Six:Conclusion and future perspective
        6.1 Conclusion
        6.2 future perspective
    Chapter Seven: References
    Chapter Eight: Appendices
        Appendix 1-Information and Consent Form
        Appendix 2- Questionnaire
        Appendix 3- The formula to calculate the Reticulocytes count
        Appendix 4- Red blood cell indices, the formula for calculation
        Appendix 5- Buffers and solutions
        Appendix 6- Equipment
        Appendix 7- Software
        Appendix 8- cell cycle Phases
Dedication
Acknowledgements
List of Publications
Published work
附件


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