Doctoral Dissertations

Keywords and Phrases

Advanced Analytical Techniques; Cancer Biomarkers; Early Cancer Detection; Liquid Chromatography - Tandem Mass Spectrometry; Pteridines

Abstract

"The development of new screening methods for the early detection of cancer remains one of the foremost challenges facing modern cancer research. The emergence of new analytical technologies and their application to 'omics'-based approaches has provided researchers with powerful new tools for molecular biomarker discovery that may benefit early screening of cancer. This dissertation outlines several key advances made toward the application of urinary metabolomics to cancer biomarker discovery. The term urinary metabolomics here refers to the investigation of small metabolites in urine as potential disease biomarkers. The advantage of using this approach lies in its noninvasive sampling characteristics and robust analytical feasibility. The dissertation begins with the development of two analytical methods for the determination of sarcosine in urine for the early detection of prostate cancer. The next three papers discuss the analytical challenges facing the determination of pteridine derivatives in biological samples and present a new method to adjust their levels to patient hydration status and time since last urination. Briefly, pteridines and their derivatives function as intermediates in the metabolism of various vitamins and cofactors, where altered levels of pteridines have been reported in the urine of patients with several types of epithelial cancers, among other diseases. The following paper explores the possibility of using urinary metals as potential cancer biomarkers in a proof-of-concept study. The final two papers investigate the biological variation of urinary pteridines in order to better understand how urinary metabolites naturally fluctuate, and apply this information to a new method for the comprehensive determination of pteridine derivatives in urine. Taken together, this body of research presents new opportunities and challenges in the discovery of new cancer biomarkers"--Abstract, page iv.

Advisor(s)

Ma, Yinfa

Committee Member(s)

Shi, Honglan
Ercal, Nuran
Winiarz, Jeffrey G.
Semon, Julie A.

Department(s)

Chemistry

Degree Name

Ph. D. in Chemistry

Sponsor(s)

Emergence Bioscreening, LLC
National Science Foundation (U.S.)
East Asia and Pacific Summer Institutes

Publisher

Missouri University of Science and Technology

Publication Date

Spring 2017

Journal article titles appearing in thesis/dissertation

  • A novel enzymatic technique for determination of sarcosine in urine samples
  • Partial enzymatic elimination and quantification of sarcosine from alanine using liquid chromatography -- tandem mass spectrometry
  • Simultaneous detection of six urinary pteridines and creatinine by high-performance liquid chromatography -- tandem mass spectrometry for clinical breast cancer detection
  • Normalization of urinary pteridines by urine specific gravity for early cancer detection
  • High-throughput intracellular pteridinic profiling by liquid chromatography -- quadrupole time-of-flight mass spectrometry
  • Urinary metallomics as a novel biomarker discovery platform: breast cancer as a case study
  • Daily variation and effect of dietary folate on urinary pteridines
  • Development of a high-performance liquid chromatography -- tandem mass spectrometry urinary pterinomics workflow

Pagination

xvi, 185 pages

Note about bibliography

Includes bibliographic references.

Rights

© 2017 Casey Franklin Burton

Document Type

Dissertation - Open Access

File Type

text

Language

English

Thesis Number

T 11079

Electronic OCLC #

992174509

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