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

Bibliographic Details
Main Author:	Watanabe, Miki
Language:	English
Published:	Miami University / OhioLINK 2011
Subjects:	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
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=miami1322753081

id	ndltd-OhioLink-oai-etd.ohiolink.edu-miami1322753081
record_format	oai_dc
spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-miami13227530812021-08-03T05:41:25Z Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines Watanabe, Miki 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 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. 2011-12-05 English text Miami University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=miami1322753081 http://rave.ohiolink.edu/etdc/view?acc_num=miami1322753081 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	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
spellingShingle	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 Watanabe, Miki Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines
author	Watanabe, Miki
author_facet	Watanabe, Miki
author_sort	Watanabe, Miki
title	Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines
title_short	Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines
title_full	Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines
title_fullStr	Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines
title_full_unstemmed	Development of DNA aptamer as a HMGA inhibitor for cancer therapy and NMR-based metabonomics studies in human/mouse cell lines
title_sort	development of dna aptamer as a hmga inhibitor for cancer therapy and nmr-based metabonomics studies in human/mouse cell lines
publisher	Miami University / OhioLINK
publishDate	2011
url	http://rave.ohiolink.edu/etdc/view?acc_num=miami1322753081
work_keys_str_mv	AT watanabemiki developmentofdnaaptamerasahmgainhibitorforcancertherapyandnmrbasedmetabonomicsstudiesinhumanmousecelllines
_version_	1719423672470470656

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

Similar Items