by Lee Sau Yat. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 89-94). / Acknowledgements --- p.I / Abbreviation --- p.II / Abstract --- p.III / Table of content --- p.IV / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Historical background in the studies of LDL and LDLR --- p.1 / Chapter 1.2 --- Homeostasis of Cholesterol in Man --- p.4 / Chapter 1.2.1 --- Origin and catabolism of low density lipoprotein --- p.4 / Chapter 1.2.2 --- The LDL receptor --- p.6 / Chapter 1.2.3 --- LDL pathway --- p.7 / Chapter 1.2.4 --- Feedback regulatory action of LDL receptor --- p.10 / Chapter 1.3 --- Gene structure of LDL receptor promoter --- p.11 / Chapter 1.3.1 --- The LDL receptor promoter --- p.11 / Chapter 1.3.2 --- The responsive element in LDL receptor promoter --- p.13 / Chapter 1.4 --- Eukaryotic transcription factor --- p.15 / Chapter 1.5 --- Role of Gel-shifted assay in studying DNA binding protein --- p.17 / Chapter 1.6 --- Objective of the present thesis --- p.20 / Chapter Chapter 2 --- Materials and Methods --- p.21 / Chapter 2.1 --- Oligonucleotide synthesis and purification --- p.21 / Chapter 2.1.1 --- Primer construction --- p.21 / Chapter 2.1.2 --- Purification of oligonucleotides --- p.22 / Chapter 2.2 --- Recombinant plasmid construction --- p.24 / Chapter 2.2.1 --- Preparation of competent cell --- p.24 / Chapter 2.2.2 --- Preparation of phage DNA --- p.24 / Chapter 2.2.3 --- Amplification and purification of LDLR-promoter by PCR techniques --- p.26 / Chapter 2.2.3.1 --- Amplification and restriction site construction of LDLR- promoter --- p.26 / Chapter 2.2.3.2 --- Purification of the PCR product --- p.27 / Chapter 2.2.4 --- Preparation of plasmid pGCAT-A --- p.27 / Chapter 2.2.5 --- Recombinant plasmid pLDLRP-GCAT- A construction --- p.29 / Chapter 2.2.6 --- Transformation of DNA to competent cell --- p.29 / Chapter 2.2.7 --- Screening of positive clone pLDLRP- GCAT-A --- p.30 / Chapter 2.3 --- DNA sequencing --- p.31 / Chapter 2.3.1 --- Denaturing the double strand template --- p.31 / Chapter 2.3.2 --- Annealing reaction --- p.31 / Chapter 2.3.3 --- Labeling reaction --- p.32 / Chapter 2.3.4 --- Termination reaction --- p.32 / Chapter 2.3.5 --- Running and fixing the gel --- p.32 / Chapter 2.4 --- Cell culture and passage of different cell lines --- p.34 / Chapter 2.4.1 --- "Routine subculture of HepG 2, CHO, FSF, Cos-7 and FSF" --- p.34 / Chapter 2.4.2 --- "BMN, RTGH-1" --- p.34 / Chapter 2.5 --- Preparation of human LDL and LPDS --- p.36 / Chapter 2.5.1 --- Purification of LDL --- p.36 / Chapter 2.5.2 --- Purification of LPDS --- p.37 / Chapter 2.6 --- DNA transfection and CAT assay --- p.38 / Chapter 2.6.1 --- Transfection of recombinant plasmid to eukaryotic cells --- p.38 / Chapter 2.6.2 --- CAT assay --- p.39 / Chapter 2.7 --- 125I-LDL binding assay --- p.41 / Chapter 2.7.1 --- Radioactive iodination of LDL --- p.41 / Chapter 2.7.2 --- Purification of iodinated LDL --- p.41 / Chapter 2.7.3 --- Down regulation of LDL receptorin different cell lines --- p.41 / Chapter 2.7.4 --- Different Drugs treatment in HepG2 Cell line --- p.42 / Chapter 2.7.5 --- 125I-LDL binding assay --- p.43 / Chapter 2.8 --- Gel-shift mobility assay --- p.44 / Chapter 2.8.1 --- Extraction of crude nuclear extracts --- p.44 / Chapter 2.8.2 --- 5'end-labeling of synthetic oligonucleotides --- p.45 / Chapter 2.8.3 --- Purification of labeled oligonucleotides --- p.45 / Chapter 2.8.4 --- Nuclear protein and DNA binding reaction --- p.46 / Chapter 2.8.5 --- Gel-shift mobility electrophoresis by PhastSystem --- p.46 / Chapter 2.9 --- Construction of λ gt 11 cDNA library of HepG 2cell --- p.48 / Chapter 2.9.1 --- Purification of mRNA from HepG 2 --- p.48 / Chapter 2.9.2 --- cDNA preparation --- p.48 / Chapter 2.9.3 --- In-vitro packaging of phage --- p.48 / Chapter 2.9.3 --- Screening the expression library --- p.49 / Chapter Chapter 3 --- Results --- p.50 / Chapter 3.1 --- Construction of recombinant plasmid --- p.50 / Chapter 3.1.1 --- hLDLR-promoter λ 34 clone --- p.50 / Chapter 3.1.2 --- Restriction site generation in LDLR- promoter by PCR --- p.52 / Chapter 3.1.3 --- Preparation of pGCAT-A reporter plasmid --- p.55 / Chapter 3.1.4 --- Screening of pGCAT-A-LDLRP recombinant --- p.55 / Chapter 3.1.5 --- Sequencing of pGCAT-A-LDLR- promoter recombinant --- p.57 / Chapter 3.2 --- CAT assay of recombinant plasmid on transfected HepG 2 cell --- p.57 / Chapter 3.3 --- 125I-LDL binding assay --- p.57 / Chapter 3.3.1 --- 125 I - LDL binding assay of different cell lines --- p.57 / Chapter 3.3.2 --- Characterization of cell surface receptor of HepG 2 cell by different drugs treatment --- p.61 / Chapter 3.4 --- Gel shift mobility assay --- p.63 / Chapter 3.4.1 --- Binding effect of Repeat 2 to different cell lines --- p.63 / Chapter 3.4.2 --- Optimizing the binding reactionin HepG 2 cell by poly(dI.dC) --- p.63 / Chapter 3.4.3 --- Specificity of Repeat 2 in binding to HepG 2 cell nuclear protein --- p.66 / Chapter 3.4.4 --- LDL dose response treatment in HepG2 cell --- p.68 / Chapter 3.4.4.1 --- Binding of Repeat 2 to specific nuclear protein --- p.68 / Chapter 3.4.4.2 --- Binding of Repeat 2 to a non- specific cell nuclear protein from cells treated with LDL --- p.68 / Chapter 3.4.5 --- Effect of different drugs on the binding of Repeat 2 to nuclear proteins in HepG 2 cell --- p.71 / Chapter 3.5 --- HepG 2 cell cDNA library screening --- p.73 / Chapter Chapter 4 --- Discussion --- p.77 / Chapter 4.1 --- Strategy on construction of reporter plasmid pLDLRP-GC AT-A --- p.77 / Chapter 4.2 --- The expression of CAT in HepG 2 cell --- p.78 / Chapter 4.3 --- Identification of a DNA binding protein for Repeat 2 in HepG 2 cell --- p.80 / Chapter 4.3.1 --- Binding effect of nuclear protein to Repeat 2 --- p.82 / Chapter 4.3.1.1 --- LDL dose response relationships --- p.82 / Chapter 4.3.1.2 --- Effect of protein inhibitors --- p.83 / Chapter 4.3.1.3 --- Effect of Shanzha --- p.86 / Chapter 4.3.2 --- Screening of the cDNA library of HepG 2 cells --- p.86 / Chapter Chapter 5 --- Further Studies --- p.88 / References --- p.89 / Appendix --- p.95

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

by Alexandra M. Leung. / Thesis (M. Phil.)--Chinese University of Hong Kong, 1981. / Bibliography: leaves 208-224.

Lipoprotein binding and metabolism in actively-dividing (subconfluent) and quiescent (postconfluent) bovine aortic endothelial cells (ECs) were qualitatively investigated by fluorescence microscopy using dioctadecylindocarbocyanine-labelled lipoproteins and by indirect immunofluorescence microscopy. LDL and acetylated-LDL (AcLDL) were seen bound to the surfaces of subconfluent ECs (at 4°C or at 37°C), as a random distribution of punctate foci. ECs therefore closely resembled fibroblasts in the distribution of LDL receptors on their surfaces. No binding of LDL was seen on postconfluent EC surfaces by either direct or indirect fluorescence microscopy. The patterns of AcLDL binding on postconfluent ECs resembled those on subconfluent ECs. Intracellular LDL and AcLDL occurred as perinuclear accumulations of large fluorescent disc-shaped profiles in subconfluent ECs. These accumulations were shown to arise from surface-bound material by pulse-chase experiments. Intracellular LDL was absent in the majority of postconfluent ECs, while AcLDL accumulation was massive. "Wounding" of cultures allowed simultaneous assessment of lipoprotein metabolism in quiescent and actively-dividing areas of the same culture. Quantitative assessments of the above-mentioned phenomena were made using ¹²⁵I-labelled lipoproteins. Receptor-mediated binding of LDL decreased five to ten-fold as the cultures modulated from subconfluent to postconfluent morphology. No receptor-bound LDL was detected in postconfluent ECs. Conversely, the amount of AcLDL bound increased at least fivefold during EC growth in parallel cultures. The amounts of lipoproteins endocytosed and metabolised were generally related proportionately to the amounts bound in each case. The distribution of LDL receptors on cultured cells was also investigated at the ultrastructural level using colloidal gold-conjugated LDL as a probe, and similarly labelled antibodies as probes. Whole-mounted cells with receptor probes bound to them were examined directly in the transmission electron microscope. The topographical distribution of LDL receptors has not been investigated by these techniques before. A novel method of preparing cytochemically-labelled, whole-mounted cells from styrene culture dishes was developed and used in this study. LDL Receptors expressed on the surfaces of human skin fibroblasts served to standardise these colloidal gold techniques and fortuitously led to new information on receptor distribution. Normal (FGo) and LDL receptor-negative mutant fibroblasts (GM 2000) acted as positive and negative controls respectively. Normal fibroblast LDL receptors were grouped into clusters consistent in size with coated pits (200 - 500 nm in diameter). A novel finding was the presence of a diffuse population of receptors scattered randomly amongst the clustered receptors. Another mutant fibroblast, GM 2408A, known to have an aberrant LDL receptor distribution, was also examined. Its receptors were shown to be dispersed singly, and in occasional groups of two and three, at random over the cell surfaces. No clusters were detected. The receptor-negative GM 2000 bound virtually no probes. While not as sensitive as the colloidal gold-conjugated LDL probe, an antireceptor monoclonal antibody (IgG-C7), localised by indirect immunogold labelling, gave similar results when applied to the above cells. This was taken as strong corroborative evidence that the LDL receptor distributions as determined by colloidal gold-conjugated LDL were correct. It is suggested that the dispersed population of receptors on normal fibroblasts may represent newly-emerged recycling receptors which have yet to cluster in coated pits. A further new finding reported here is the existence of the same two patterns of LD L receptors, dispersed and clustered, on the surface of subconfluent ECs. It was noted, from the study of whole-mounted and thin-sectioned cells, that the receptors were preferentially arranged in rings following the circumference of coated pit areas on the cell surface. Often these rings associated in groups or even coalesced into compound clusters. The significance of these groupings is not yet understood. In sharp contrast to the situation on subconfluent ECs, no LDL receptors (probed with the extremely sensitive colloidal-gold conjugated LDL) could be detected at the EM level on the surface of postconfluent ECs. Active cells in wounded postconfluent monolayers expressed abundant receptors detected at the EM level. It is concluded that postconfluent quiescent bovine aortic ECs in vitro metabolise virtually no LDL via the LDL-receptor pathway due to a vanishingly low number of LDL receptors. This contrasts with the ability of postconfluent cells to metabolise relatively large amounts of AcLDL via a receptor-mediated mechanism. The significance of these conclusions is discussed with respect to the interaction of plasma lipoproteins with the endothelium in vivo.

by Lo Hoi Ka Elka. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 172-181). / Abstracts in English and Chinese. / ABSTRACT --- p.i / 摘要 --- p.iv / LIST OF TABLES AND FIGURES --- p.viii / ABBREVIATIONS --- p.xiv / Chapter CHAPTER 1 : --- INTRODUCTION / Chapter 1.1. --- DIFFERENT TREATMENTS OF THE CANCER THERAPY --- p.1 / Chapter 1.2. --- THE SIDE EFFECTS OF CANCER TREATMENT / Chapter 1.2.1. --- Surgery --- p.1 / Chapter 1.2.2. --- Radiotherapy --- p.2 / Chapter 1.2.3. --- Chemotherapy --- p.2 / Chapter 1.3. --- THE CHARACTERISTICS OF DOXORUBICIN (DOX) / Chapter 1.3.1. --- The structure of Dox --- p.6 / Chapter 1.3.2. --- The actions of Dox --- p.8 / Chapter 1.3.3. --- The adverse side effect of Dox --- p.8 / Chapter 1.4. --- THE RATIONALE OF USING LOW DENSITY LIPOPROTEIN (LDL) AS A TARGET CARRIER IN CANCER THERAPY / Chapter 1.4.1. --- The correlation between cholesterol and cancer --- p.9 / Chapter 1.4.2. --- Low density lipoprotein (LDL) as a target carrier --- p.11 / Chapter 1.4.3. --- The down and up regulation of LDL receptors --- p.14 / Chapter 1.4.4. --- The characteristics of Fuctus Craegus (FC) --- p.15 / Chapter 1.5. --- DIFFERENT METHODS OF THE PREPARATION OF THE LOW DENSITY LIPOPROTEIN-DRUG (LDL- DRUG) --- p.18 / Chapter 1.6. --- THE CHARACTERISTICS OF LOW DENSITY LIPOPROTEIN (LDL) / Chapter 1.6.1. --- The structure of LDL --- p.20 / Chapter 1.6.2. --- The metabolic pathway of LDL in human bodies --- p.23 / Chapter 1.7. --- THE MULTIDRUGS RESISTANCE IN TUMOR CELLS --- p.25 / Chapter 1.7.1. --- The mechanism of multidrug resistance --- p.27 / Chapter 1.7.2. --- The structure of P-glycoprotein --- p.27 / Chapter 1.7.3. --- The mechanism of P-glycoprotein --- p.30 / Chapter 1.8. --- COMBINED TREATMENT WITH HYPERTHERMIA --- p.31 / Chapter 1.9. --- AIM OF THE STUDY --- p.33 / Chapter CHAPTER 2 : --- MATERIALS AND METHODS / Chapter 2.1. --- MATERIALS / Chapter 2.1.1. --- Animals --- p.34 / Chapter 2.1.2. --- Buffers --- p.34 / Chapter 2.1.3. --- Cell culture reagents --- p.36 / Chapter 2.1.4. --- Chemicals --- p.38 / Chapter 2.1.5. --- Culture of cells --- p.40 / Chapter 2.2. --- METHODS / Chapter 2.2.1. --- In vitro studies / Chapter 2.2.1.1. --- "LDL, doxorubicin complex formation" --- p.41 / Chapter 2.2.1.2. --- Determination of the concentration of LDL-Dox --- p.42 / Chapter 2.2.1.3. --- In vitro cytotoxicity --- p.43 / Chapter 2.2.1.4. --- The cytotoxicity of the combined treatment with anticancer drugs --- p.44 / Chapter 2.2.1.5. --- The preparation of Fructus Crataegus (FC) --- p.46 / Chapter 2.2.1.6. --- Western blot --- p.47 / Chapter 2.2.1.7. --- Flow cytometry --- p.49 / Chapter 2.2.1.8. --- Confocal laser scanning microscopy --- p.52 / Chapter 2.2.2. --- In vivo studies / Chapter 2.2.2.1. --- Subcutaneous injection of R-HepG2 cells in nude mouse --- p.55 / Chapter 2.2.2.2. --- Treatment schedules --- p.55 / Chapter 2.2.2.3. --- Assay of investigating of the myocardial injury --- p.56 / Chapter 2.2.2.4. --- Tissue preparation procedure for light microscope (LM) --- p.57 / Chapter 2.2.3. --- Statistical analysis in our research --- p.59 / Chapter CHAPTER 3 : --- RESULTS / Chapter 3.1. --- in vitro STUDIES / Chapter 3.1.1. --- The preparation of low density lipoprotein-doxorubicin (LDL-Dox) --- p.60 / Chapter 3.1.2. --- Studies on human hepatoma cells line (HepG2 cells) / Chapter 3.1.2.1. --- The comparison of Dox and LDL-Dox accumulated in HepG2 cells --- p.63 / Chapter 3.1.2.2. --- Confocal laser scanning microscopic (CLSM) studies on the accumulation of Dox and LDL-Dox in HepG2 cells --- p.65 / Chapter 3.1.2.3. --- The comparsion of the cytotoxicity of Dox and LDL-Dox on HepG2 cells --- p.67 / Chapter 3.1.2.4. --- The comparison of the cytotoxicty of Dox and LDL-Dox with and without hyperthermia on HepG2 cells --- p.73 / Chapter 3.1.2.5. --- The comparison of accumulation of Dox and LDL-Dox in HepG2 cells treated with and without combination of with hyperthermia --- p.77 / Chapter 3.1.2.6. --- Confocal laser scanning microscopic (CLSM) studies on the accumulation of Dox and LDL-Dox in HepG2 treated cells with and without hyperthermia --- p.80 / Chapter 3.1.2.7. --- Modulation of LDL receptors on HepG2 cells------Up- regulation of LDL receptors by Fructus Craegtus (FC) / Chapter 3.1.2.7.1. --- The comparsion of LDL receptor expression on HepG2 cells after Fructus Craegtus (FC) pre-treatment --- p.83 / Chapter 3.1.2.7.2. --- The comparison of accumulation of LDL-Dox accumulated in HepG2 cells pre-treated with and without Fructus Craegtus (FC) --- p.85 / Chapter 3.1.2.7.3. --- Confocal laser scanning microscopic (CLSM) studies on the accumulation of LDL-Doxin HepG2 cells after Fructus Craegtus (FC) pre- treatment --- p.88 / Chapter 3.1.2.7.4. --- Cytotoxicity of combined treatment with LDL-Dox and Fructus Craegtus (FC) --- p.91 / Chapter 3.1.3. --- Studies on multidrug human resistant hepatoma cell line (R-HepG2 cells) / Chapter 3.1.3.1. --- The overexpression level of P-glycoprotein in resistant cell line R-HepG2 --- p.93 / Chapter 3.1.3.2. --- The comparison of Dox and LDL-Dox accumulated in R- HepG2 cells --- p.95 / Chapter 3.1.3.3. --- Confocal laser scanning microscopic (CLSM) studies on the accumulation of Dox and LDL-Dox in R-HepG2 cells --- p.97 / Chapter 3.1.3.4. --- The comparsion of the cytotoxicity of Dox and LDL-Dox on R-HepG2 cells --- p.99 / Chapter 3.1.3.5. --- The comparison of the cytotoxicty of Dox and LDL-Dox with and without hyperthermia on R-HepG2 cells --- p.109 / Chapter 3.1.3.6. --- The comparison of the accumulation of Dox and LDL- Dox in R-HepG2 cells treated in combination with hyperthermia --- p.113 / Chapter 3.1.3.7. --- Confocal laser scanning microscopic (CLSM) studies on the accumulation of Dox and LDL-Dox in R-HepG2 cells with and without hyperthermia --- p.117 / Chapter 3.1.3.8. --- Modulation of LDL receptors on R-HepG2 cells ------ Up-regulation of LDL receptors by Fructus Craegtus (FC) / Chapter 3.1.3.8.1. --- The comparsion of LDL receptor expression on R-HepG2 cells after Fructus Craegtus (FC) pre-treatment --- p.120 / Chapter 3.1.3.8.2. --- The comparsion of the accumulation of LDL- Dox in R-HepG2 cells after Fructus Craegtus (FC) pre-treatment --- p.122 / Chapter 3.1.3.8.3. --- Confocal laser scanning microscopic (CLSM) studies in the accumulation of LDL-Dox by Fructus Craegtus pre-treatment in R-HepG2 cells --- p.125 / Chapter 3.1.3.8.4. --- The comparison of cytotoxicity of combined treatment with LDL-Dox and Fructus Craegtus (FC) in R-HepG2 cells --- p.128 / Chapter 3.2. --- in vivo STUDIES / Chapter 3.2.1. --- The comparison of Dox and LDL-Dox on reducing the tumor sizes and weight in nude mice bearing R-HepG2 cells / Chapter 3.2.1.1. --- The comparison of Dox and LDL-Dox on reducing the tumor size in nude mice bearing R-HepG2 cells --- p.130 / Chapter 3.2.1.2. --- The comparison of Dox and LDL-Dox on reducing the tumor weight in nude mice bearing R-HepG2 cells --- p.138 / Chapter 3.2.2. --- Myocardial injury measured by Lactate dehydrogenase (LDH) activity in nude mice bearing R-HepG2 cells treated with Dox and LDL-Dox --- p.140 / Chapter 3.2.3. --- Myocardial injury measured by Creatine kinase (CK) activity in nude mice bearing R-HepG2 cells treated with Dox and LDL-Dox --- p.143 / Chapter 3.2.4. --- Histological studies of heart of nude mice bearing R-HepG2 cells treated with Dox and LDL-Dox / Chapter 3.2.4.1. --- Heart section of nude mice --- p.146 / Chapter 3.2.4.2. --- Heart section of nude mice bearing R-HepG2 cells --- p.148 / Chapter 3.2.4.3. --- Heart section of lmg/kg Dox treated nude mice bearing R- HepG2 cells --- p.150 / Chapter 3.2.4.4. --- Heart section of 2mg/kg Dox treated nude mice bearing R- HepG2 cells --- p.152 / Chapter 3.2.4.5. --- Heart section of lmg/kg LDL-Dox treated nude mice bearing R-HepG2 cells --- p.154 / Chapter CHAPTER 4 --- : DISCUSSION / Chapter 4.1. --- in vitro STUDIES / Chapter 4.1.1. --- The cytotoxicity of Dox and LDL-Dox on HepG2 cells and R- HepG2 cells --- p.156 / Chapter 4.1.2. --- The combined treatment on HepG2 cells and R-HepG2 cells --- p.157 / Chapter 4.1.3. --- The modulation of LDL-R expression --- p.159 / Chapter 4.2. --- in vivo STUDIES --- p.162 / Chapter CHAPTER 5 --- : CONCLUSION / Chapter 5.1. --- CONCLUSION / Chapter 5.1.1. --- In vitro studies --- p.167 / Chapter 5.1.2. --- In vivo studies --- p.169 / Chapter 5.2. --- FUTURE PROSPECTIVE --- p.170 / REFERENCES --- p.172

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

by Chu Chi Yuen, Andrew. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 140-153). / Abstract also in Chinese. / ABSTRACT --- p.i / Chapter 1 --- INTRODUCTION --- p.3 / Chapter 1.1 --- Using Low density lipoprotein (LDL) as a drug carrier --- p.4 / Chapter 1.1.1 --- The structure of Low density lipoprotein (LDL) --- p.4 / Chapter 1.1.2 --- The metabolic pathway of LDL in human bodies --- p.4 / Chapter 1.1.3 --- The rationale for using LDL as a drug carrier --- p.7 / Chapter 1.1.4 --- Reconstitution of LDL with cytotoxic drugs --- p.9 / Chapter 1.1.5 --- Up and down regulation of LDL receptors --- p.11 / Chapter 1.2 --- Doxorubicin (DOX) --- p.12 / Chapter 1.2.1 --- Characteristics of DOX --- p.12 / Chapter 1.2.2 --- Drug actions of DOX --- p.14 / Chapter 1.2.3 --- The adverse side effects of DOX --- p.15 / Chapter 1.3 --- Multidrug resistance phenomenon in tumor cells --- p.17 / Chapter 1.3.1 --- The possible mechanisms of multidrug resistance --- p.19 / Chapter 1.3.2 --- The structure of P-glycoprotein --- p.20 / Chapter 1.3.3 --- The mechanisms of the P-glycoprotein --- p.22 / Chapter 1.3.4 --- Our aim in dealing with multidrug resistance --- p.22 / Chapter 2 --- MATERIALS AND METHODS --- p.23 / Chapter 2.1 --- Materials --- p.23 / Chapter 2.1.1 --- Animals --- p.23 / Chapter 2.1.2 --- Buffers --- p.24 / Chapter 2.1.3 --- Culture media --- p.25 / Chapter 2.1.4 --- Chemicals --- p.26 / Chapter 2.1.5 --- Culture of cells --- p.27 / Chapter 2.2 --- Methods --- p.29 / Chapter 2.2.1 --- In vitro studies --- p.29 / Chapter 2.2.2 --- In vivo studies --- p.44 / Chapter 3 --- RESULTS --- p.51 / Chapter 3.1 --- In vitro studies --- p.51 / Chapter 3.1.1 --- Preparation of LDL-DOX --- p.51 / Chapter 3.1.2 --- Comparison of the cytotoxicity of DOX and LDL-DOX on HepG2 cells --- p.59 / Chapter 3.1.3 --- Modulation of LDL receptors on HepG2 cells and ECV304 cells… --- p.63 / Chapter 3.1.4 --- The effect of combined treatment of LDL-DOX and hyperthermia on HepG2 cells --- p.84 / Chapter 3.1.5 --- The effect of LDL-DOX on resistant cell line R-HepG2 cells --- p.90 / Chapter 3.2 --- In vivo studies --- p.105 / Chapter 3.2.1 --- The comparison of organ distribution of LDL-DOX and DOXin BALB-c mice after administration --- p.105 / Chapter 3.2.2 --- The comparison of organ distribution of LDL-DOX and DOX in nude mice bearing HepG2 cells after adminstration --- p.108 / Chapter 3.2.3 --- Histological studies of heart of nude mice bearing HepG2 cells treated with DOX and LDL-DOX --- p.111 / Chapter 3.2.4 --- Myocardial injury measured by Lactate dehydrogenase (LDH) activity in nude mice bearing HepG2 treated with DOX and LDL- DOX --- p.117 / Chapter 3.2.5 --- The comparison of DOX and LDL-DOX on reducing the tumor sizes and weight in nude mice bearing HepG2 cells --- p.119 / Chapter 4 --- DISCUSSION --- p.122 / Chapter 4.1 --- In vitro studies --- p.122 / Chapter 4.1.1 --- Preparation of LDL-DOX complex --- p.122 / Chapter 4.1.2 --- The cytotoxicity ofLDL-DOX --- p.125 / Chapter 4.1.3 --- The combined treatment of hyperthermia and LDL-DOX --- p.129 / Chapter 4.1.4 --- The ability of LDL-DOX to circumvent muiltidrug resistance --- p.131 / Chapter 4.2 --- In vivo studies --- p.134 / Chapter 5 --- CONCLUSION --- p.136 / Chapter 5.1 --- Conclusion --- p.136 / Chapter 5.2 --- Future pospective --- p.139 / BIBLIOGRAPHY --- p.140

by Chan Chi Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 119-137). / Chapter SECTION 1 --- INTRODUCTION / Chapter 1.1 --- Overview on lipids --- p.2 / Chapter 1.1.1 --- Definition and Classification of Lipids --- p.2 / Chapter 1.1.2 --- Lipoproteins and Apolipoproteins --- p.4 / Chapter 1.1.3 --- Outline of Lipoprotein Metabolism --- p.9 / Chapter 1.1.4 --- LDL Metabolism --- p.12 / Chapter 1.2 --- Dyslipidaemia and Cardiovascular Disease (CVD) --- p.16 / Chapter 1.2.1 --- Definition --- p.16 / Chapter 1.2.2 --- Dyslipidaemia and CAD --- p.16 / Chapter 1.2.3 --- Dyslipidaemia in Non-Insulin Dependent Diabetes Millitus Patients --- p.18 / Chapter 1.2.4 --- Claasification of Dyslipidaemia --- p.24 / Chapter 1.2.5 --- Causes of Hyperlipidaemia --- p.26 / Chapter 1.3 --- Dyslipidaemia and Atherosclerosis --- p.29 / Chapter 1.3.1 --- Pathogenesis of Atherosclerosis --- p.29 / Chapter 1.3.2 --- Mechanism of Atherogenesis --- p.31 / Chapter 1.3.3 --- Intrinsic Roles of LDL in Atherogenesis --- p.33 / Chapter (1) --- LDL Oxidizability --- p.33 / Chapter (2) --- LDL Particle Size Heterogeneity --- p.39 / Chapter 1.4 --- Management of Dyslipidaemia --- p.42 / Chapter 1.5 --- Aims of This Study --- p.49 / Chapter SECTION 2 --- MATERIALS AND METHODS / Chapter 2.1 --- Materials --- p.52 / Chapter 2.1.1 --- Patients and Controls --- p.52 / Chapter 2.1.2 --- Drug Administration Trials --- p.54 / Chapter 2.1.3 --- Blood Samples --- p.55 / Chapter 2.1.4 --- Biochemicals --- p.56 / Chapter 2.1.5 --- Solutions and Buffers --- p.56 / Chapter 2.1.6 --- Apparatus and Equipment --- p.60 / Chapter 2.2 --- Methods --- p.62 / Chapter 2.2.1 --- General Clinical Biochemistry Tests --- p.62 / Chapter 2.2.2 --- Apolipoprotein Assays --- p.62 / Chapter 2.2.3 --- Ultracentrifugation of LDL Fraction --- p.63 / Chapter 2.2.4 --- De-Salting of LDL Fraction --- p.64 / Chapter 2.2.5 --- Qualitative Determination of LDL-Cholesterol and Protein Fractions --- p.64 / Chapter 2.2.6 --- In Vitro Assessment of LDL Oxidizability --- p.65 / Chapter 2.2.7 --- Electrophoretic Gel Pattern of LDL Fraction During In Vitro Oxidizability --- p.65 / Chapter 2.2.8 --- Study of LDL Particle Size --- p.66 / Chapter 2.2.9 --- Statistical Analysis --- p.67 / Chapter SECTION 3 --- RESULTS / Chapter 3.1 --- Quantitative Determination and Standardization of LDL Fractions --- p.69 / Chapter 3.2 --- In Vitro Assessment of LDL Oxidizability --- p.72 / Chapter 3.3 --- Electrophoretic Patterns of LDL during In Vitro Oxidizability --- p.72 / Chapter 3.4 --- LDL Sizing --- p.73 / Chapter 3.5 --- "Correlations of Triglycerides Concentration, LDL Particle Size and Oxidizability" --- p.76 / Chapter 3.6 --- Diabetes Millitus --- p.83 / Chapter 3.6.1 --- NIDDM Patients & Controls --- p.83 / Chapter 3.6.2 --- Effect of Drug Treatment on Serum Lipid-Lipoprotein- Apolipoprotein Profile --- p.86 / Chapter 3.7 --- Hypertriglyceridaemic Patients --- p.90 / Chapter 3.7.1 --- Patients & Controls --- p.90 / Chapter 3.7.2 --- Bezafibrate Treatment --- p.91 / Chapter 3.8 --- CAD Patients --- p.97 / Chapter 3.8.1 --- CAD Patients & Controls --- p.97 / Chapter SECTION 4 --- DISCUSSION / Chapter 4.1 --- Patients and Controls --- p.101 / Chapter 4.2 --- Ultracentrifugation of LDL Fractions --- p.102 / Chapter 4.3 --- In Vitro LDL Oxidizability --- p.103 / Chapter 4.4 --- "Association of TG, LDL Oxidizability and Particle Size" --- p.105 / Chapter 4.5 --- LDL Sizing --- p.106 / Chapter 4.6 --- Comparsion of Patients and Controls in Lipid-Lipoprotein- Apolipoprotein Profiles --- p.107 / Chapter 4.7 --- The Effect of Lovastatin and Acipimox on NIDDM Patients --- p.111 / Chapter 4.8 --- The Effect of Bezafibrate on Hypertriglyceridaemic Patients --- p.114 / Chapter SECTION 5 --- CONCLUSION --- p.116 / References --- p.119 / Appendices --- p.138

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Virginia, 1999. / Spine title: The regulation of LRP in the CNS. Includes bibliographical references. Also available online through Digital Dissertations.