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Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines

Watanabe, Miki
http://rave.ohiolink.edu/etdc/view?acc_num=miami1322753081

Abstract Details

2011, Doctor of Philosophy, Miami University, Chemistry and Biochemistry.
The first part of this dissertation describe the characterization of the DNA binding activity of high mobility group A (HMGA) protein and provide an analysis of the use of a DNA aptamer as a potential cancer 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.
Michael A Kennedy (Advisor)
Christopher A Makaroff (Committee Chair)
Michael W Crowder (Committee Member)
Gary A Lorigan (Committee Member)
Qingshun Quinn Li (Committee Member)
263 p.
Biochemistry; Cellular Biology; Molecular Biology
HMGA; phosphorothioate DNA; DNA aptamer; pancreatic cancer; gemcitabine; PCA; NMR; metabonomics; metabolic profiling; skeletal muscle cell; DAG; burn injury; breast cancer cell line; NPY; Y5R; CGP;

Recommended Citations

Citations

  • Watanabe, M. (2011). Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1322753081

    APA Style (7th edition)

  • Watanabe, Miki. Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines. 2011. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1322753081.

    MLA Style (8th edition)

  • Watanabe, Miki. "Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines." Doctoral dissertation, Miami University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=miami1322753081

    Chicago Manual of Style (17th edition)

miami1322753081
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© 2011, all rights reserved.
This open access ETD is published by Miami University and OhioLINK.