Wong, Ling Yee. / Thesis submitted in: August 2007. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 110-127). / Abstracts in English and Chinese. / Thesis Abstract --- p.i / 論文摘要 --- p.iv / Acknowledgements --- p.vi / Abbreviations --- p.vii / Thesis Content --- p.xii / List of Figures --- p.xv / List of Tables --- p.xvii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Literature Review --- p.3 / Chapter 2.1. --- Multiple Myeloma (MM) --- p.3 / Chapter 2.1.1 --- Epidemiology --- p.4 / Chapter 2.1.2 --- Cause and Risk Factors --- p.5 / Chapter 2.1.3 --- Pathophysiology --- p.5 / Chapter 2.1.4 --- Diagnosis and Clinical Presentation --- p.6 / Chapter 2.1.5 --- Classification of Plasma Cell Disorders --- p.6 / Chapter 2.1.5.1 --- Monoclonal Gammopathy of Undetermined Significance (MGUS) --- p.6 / Chapter 2.1.5.2 --- Asymptomatic (Smouldering) MM --- p.7 / Chapter 2.1.5.3 --- Indolent MM --- p.7 / Chapter 2.1.5.4 --- Symptomatic MM --- p.8 / Chapter 2.1.6 --- Staging --- p.9 / Chapter 2.1.7 --- Treatment --- p.11 / Chapter 2.1.8 --- Molecular Abnormality --- p.12 / Chapter 2.2 --- DNA Microarray Analysis in MM --- p.13 / Chapter 2.2.1 --- MM Pathogenesis --- p.15 / Chapter 2.2.2 --- Molecular Classification of MM --- p.18 / Chapter 2.2.3 --- Anti-MM Drug Studies --- p.22 / Chapter 2.3 --- Cancer Treatment Response Prediction --- p.24 / Chapter 2.3.1 --- MP Treatment --- p.24 / Chapter 2.3.1.1 --- Melphalan --- p.25 / Chapter 2.3.1.2 --- Prednisone --- p.27 / Chapter 2.3.1.3 --- MP Treatment Response Prediction in MM --- p.29 / Chapter 2.3.2 --- Cancer Prognosis using DNA Microarray --- p.31 / Chapter Chapter 3 --- Materials and Methods --- p.36 / Chapter 3.1. --- Patient Specimens for Gene Expression Profiling and Quantitative Real-time PCR --- p.36 / Chapter 3.2. --- Magnetic Cell Sorting of CD138-positive Plasma Cells --- p.37 / Chapter 3.2.1 --- Density Gradient Centrifugation --- p.37 / Chapter 3.2.2 --- Positive Selection of CD138-positive Cells --- p.37 / Chapter 3.3 --- Generation of Gene Expression Profiles --- p.39 / Chapter 3.3.1 --- RNA Extraction --- p.39 / Chapter 3.3.2 --- RNA Assessment --- p.40 / Chapter 3.3.3 --- Synthesis and Purification of Double-strand cDNA --- p.40 / Chapter 3.3.4 --- In vitro Transcription (IVT) and Recovery of Biotin-labeled cRNA --- p.41 / Chapter 3.3.5 --- cRNA Fragmentation and Hybridization Reaction Mixture Preparation --- p.41 / Chapter 3.3.6 --- Hybridization --- p.42 / Chapter 3.3.7 --- Post-hybridization Wash --- p.42 / Chapter 3.3.8 --- Detection with Streptavidin-dye Conjugate --- p.43 / Chapter 3.3.9 --- Bioarray Scanning and Spot Signal Quantitation --- p.43 / Chapter 3.4 --- Microarray Data Analysis --- p.45 / Chapter 3.4.1 --- Normalization and Filtering --- p.45 / Chapter 3.4.2 --- Unsupervised Clustering Analysis --- p.45 / Chapter 3.4.3 --- Supervised Class Comparison Analysis --- p.46 / Chapter 3.5 --- Microarray Verification and Candidate Gene Validation --- p.47 / Chapter 3.5.1 --- RNA Extraction --- p.47 / Chapter 3.5.2 --- Reverse Transcription PCR --- p.47 / Chapter 3.5.3 --- Quantitative Real-time PCR --- p.48 / Chapter 3.6 --- Predictive Value Calculation --- p.49 / Chapter 3.7 --- Experimental Flow --- p.49 / Chapter Chapter 4 --- Results --- p.53 / Chapter 4.1 --- Gene Expression Profiling of Chinese MM --- p.53 / Chapter 4.1.1 --- Unsupervised Clustering Analysis --- p.53 / Chapter 4.1.1.1 --- Hierarchical Clustering --- p.53 / Chapter 4.1.1.2 --- Principal Component Analysis (PCA) --- p.54 / Chapter 4.1.2 --- Identification of Statistically Differentially Expressed Genes --- p.58 / Chapter 4.1.2.1 --- Two-Sample t-statistics --- p.58 / Chapter 4.1.2.2 --- Significance Analysis of Microarrays (SAM) --- p.58 / Chapter 4.1.2.3 --- Microarray Verification --- p.66 / Chapter 4.2 --- Development of MP Treatment Response Biomarker in MM --- p.70 / Chapter 4.2.1 --- Unsupervised Clustering Analysis --- p.70 / Chapter 4.2.1.1 --- Hierarchical Clustering --- p.70 / Chapter 4.2.1.2 --- PCA --- p.70 / Chapter 4.2.2 --- Identification of Statistically Differentially Expressed Genes --- p.74 / Chapter 4.2.2.1 --- Two sample t-statistics --- p.74 / Chapter 4.2.2.2 --- SAM --- p.74 / Chapter 4.2.3 --- Verification of Candidate Gene CYB5D1 --- p.76 / Chapter Chapter 5 --- Discussion --- p.79 / Chapter 5.1 --- Global Gene Expression Profiling: DNA Microarray --- p.79 / Chapter 5.2 --- Microarray Data Normalization and Gene Filtering --- p.81 / Chapter 5.3 --- Microarray Data Analysis --- p.83 / Chapter 5.3.1 --- Unsupervised Clustering Analysis --- p.83 / Chapter 5.3.1.1 --- Hierarchical Clustering --- p.83 / Chapter 5.3.1.2 --- PCA --- p.85 / Chapter 5.3.2 --- Identification of Statistically Differentially Expressed Genes --- p.86 / Chapter 5.4 --- Verification of Candidate Genes by Quantitative Real-time PCR --- p.89 / Chapter 5.5 --- Gene Expression Profiling of Chinese MM --- p.90 / Chapter 5.5.1 --- Comparison of Gene Expression Patterns of MM and Normal Plasma Cells --- p.90 / Chapter 5.5.2 --- Differentially Expressed Genes between MM and Normal Plasma Cells..… --- p.91 / Chapter 5.5.2.1 --- Common Differentially Expressed Genes with Previous Studies --- p.94 / Chapter 5.5.2.2 --- Potential Tumor Suppressor Genes in Differentially Expressed Genes..… --- p.96 / Chapter 5.5.2.3 --- Verified Differentially Expressed Genes --- p.98 / Chapter 5.5.3 --- Future Studies --- p.101 / Chapter 5.6 --- Development of MP Treatment Response Biomarker in MM --- p.103 / Chapter 5.6.1 --- Comparison of Gene Expression Patterns of MP Good Responders (GR) and Poor Responders (PR) --- p.103 / Chapter 5.6.2 --- Differentially Expressed Gene between MP GR and PR: CYB5D1 --- p.104 / Chapter 5.6.3 --- Possible Role of CYB5D1 in MP Resistance in MM Cells --- p.104 / Chapter 5.6.4 --- Potential Clinical Application of CYB5D1 in MP Treatment Response Prediction in MM --- p.106 / Chapter 5.6.5 --- Future Studies --- p.106 / Chapter Chapter 6 --- Conclusion --- p.108 / Chapter 6.1 --- Gene Expression Profiling of Chinese MM --- p.108 / Chapter 6.2 --- Development of MP Treatment Response Biomarker in MM --- p.108 / References --- p.110 / Appendix --- p.128
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_326206 |
| Date | January 2008 |
| Contributors | Wong, Ling Yee., Chinese University of Hong Kong Graduate School. Division of Anatomical and Cellular Pathology. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | print, xvii, 128 leaves : ill. (some col.) ; 30 cm. |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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