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Dissertation/Thesis Abstract

Methods for profiling glycans for disease marker discovery
by Kirmiz, Crystal, Ph.D., University of California, Davis, 2009, 131; 3369931
Abstract (Summary)

It was once believed that glycans were an unnecessary part of the cell, providing only fuel. Since then much research has shown that glycans are extremely important in biological processes. Glycans are carbohydrates that are bonded to proteins in the cell, are commonly on the outside surface of a cell, can be used for cell-cell communication, such as fertilization.

The analysis of glycans is particularly difficult due to the complexity of possible structures. Unlike proteins which have a linear structure of amino acids, monosaccharides have many bonding positions and therefore can be branched leading to many positional and conformational isomers. To understand the function of glycans it is first critical to be able to identify the structures present. Many different technologies exist to assist in the identification of carbohydrates including high performance liquid chromatography and mass spectrometry.

Breast cancer is the second most common cause of cancer mortality among women. Since the early symptoms of breast cancer are minimal, early detection is virtually impossible. By the time the breast cancer is diagnosed, it can be so advanced that it becomes untreatable. If a biomarker existed that could indicate the presence of cancer in the early stages it could be a significant breakthrough for diagnosticians. The work here utilizes glycans as a possible biomarker for breast cancer.

Prostate cancer is the most common type of cancer found in American men. Either surgery or radiation therapy can be used to successfully treat prostate cancer in the early stages. However, once prostate cancer becomes metastatic, there is no current method known to cure it. In this work a comparison is made between glycans extracted from cells of prostate cancer cell lines to determine if variations are observed, in the hopes of discovering potential prostate cancer biomarkers.

The study of serum glycans, in particular N-linked, is advantageous for disease marker discovery. Many methods are available for the study of N-linked glycans. Several of these methods are not viable for biological levels of glycans. A nano-LC/MS method is presented here to analyze underivatized biological levels of N-linked glycans for online nano-LC/MS analysis.

Indexing (document details)
Advisor: Lebrilla, Carlito B.
Commitee: Augustine, Matthew P., Ng, Cheuk-Yiu
School: University of California, Davis
Department: Chemistry
School Location: United States -- California
Source: DAI-B 70/08, Dissertation Abstracts International
Subjects: Analytical chemistry
Keywords: Biomarkers, Cancer, Fourier transform mass spectrometry, Glycans, High-performance liquid chromatography
Publication Number: 3369931
ISBN: 978-1-109-32656-7
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