(DOWNLOAD) "Development of DNA Aptamer as a HMGA Inhibitor for Cancer Therapy and NMR-Based Metabonomics Studies in Human/Mouse Cell Lines" by Miki Watanabe * eBook PDF Kindle ePub Free
eBook details
- Title: Development of DNA Aptamer as a HMGA Inhibitor for Cancer Therapy and NMR-Based Metabonomics Studies in Human/Mouse Cell Lines
- Author : Miki Watanabe
- Release Date : January 19, 2013
- Genre: Science & Nature,Books,Professional & Technical,Medical,
- Pages : * pages
- Size : 24885 KB
Description
The first part of this dissertation describes the characterization of the DNA binding activity of high mobility group A (HMGA) protein and provides an analysis of the use of a DNA aptamer as a potentialcancer therapeutic treatment in human pancreatic cancer cell lines. The second part describes the application of NMR-based metabonomics in mammalian cell line studies. Chapter 1 provides a background on the current knowledge of HMGA and its role in cancer, as well as an introduction to NMR-based metabonomics and its use in cell line studies. Chapter 2 presents the characterization of HMGA/DNA complex formation using electro mobile shift away and isothermal calorimetry. Based on this study, a HMGA-targeted, DNA aptamer inhibitor was designed, and its effect on cancer cell growth was examined in human pancreatic cancer cell lines. This HMGA inhibitor study, discussed in Chapter 3, also examined the effect of the co-treatment using the DNA aptamer together with the chemotherapy reagent, gemcitabine, which showed significant decrease in pancreatic cancer cell viability. Chapters 4, 5, and 6 describe cell line metabonomics studies using NMR spectroscopy. Cell line metabonomics are useful for the identification of potential biomarkers for a certain disease. Chapter 4 describes a comparative study of metabolic profiles of three human pancreatic cancer cell lines and a normal human pancreatic ductal epithelial cell line, H6C7. This study identified not only metabolites unique to the cancer cells compared to normal cells, but it also identified metabolic differences between cancer cell lines. Furthermore, the use of NMR-based metabonomics in cell line studies enabled identification of metabolic pathways that can be targeted by drug treatment, which can ultimately be used to monitor the effect of cancer drug therapy. Chapters 5 and 6 demonstrate the capability of NMR-based metabonomics to study the effect of drug treatments in two different systems: a burn-injury model and a breast cancer model. In both systems, several metabolites were identified as potential markers for assessing these drug treatments, and it is anticipated that this research will provide a framework for further analysis of these drugs as potential therapeutic agents. Chapter 7 summarizes the presented research and discusses future work.
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