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Date of Award

2017

Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Administrative Home Department

Department of Chemistry

Advisor 1

Tarun Dam

Committee Member 1

Lanrong Bi

Committee Member 2

Shiyue Fang

Committee Member 3

Guiliang Tang

Abstract

Thyroid cancer is the most common endocrine carcinoma. Currently, the clinical diagnosis of thyroid cancer and the therapeutic approaches to combat the disease face enormous challenges. Fine needle aspiration biopsy combined with biomarker assays are generally used in thyroid cancer detection. However, the results of the detection tests often remain ambiguous. The difficulty in distinguishing between benign and malignant tumors makes many patients undergo unnecessary surgical procedures. Therefore, accurate diagnostic methods and highly effective anti-tumor treatment options are needed to increase the quality of management of thyroid cancer patients. My dissertation includes two projects that contribute to the improvement of thyroid cancer detection and possible therapy. Thyroglobulin (Tg) and Galectin-3 (Gal-3) are both well-known thyroid cancer biomarkers that are overexpressed in thyroid tumor cells. Data presented in my dissertation show that Tg and Gal-3 bind to each other with high affinity (nM) and form complexes that block both molecules from clinical detection. This mechanism can potentially introduce inaccuracies in thyroid cancer biomarker assay. More importantly, since many glycoprotein cancer biomarkers contain binding epitopes for Gal-3, biomarker masking interaction, observed in the present study, might occur in other types of cancer as well. My second project deals with the purification and characterization of a new saponin-like glycoside named HelyX lysin. Certain glycosides have been shown to have cytotoxic effects on thyroid cancer cells. Therefore, every newly discovered glycoside needs to be checked for possible effects they might have on cancer cells including those from thyroid carcinoma. HelyX lysin contains strong hemolytic activity and exhibits potential anti-fungal and anti-tumor properties. Interestingly, the hemolysis of HelyX lysin can be inhibited by human serum glycoproteins. This property has never been reported for any other saponin-like glycosides. Controlling hemolysis by glycoproteins might be a viable strategy for overcoming the unfavorable hemolytic activity of HelyX lysin during its medical applications. The discovery of the glycan-mediated interactions between two biomarkers, and the characterization of a potential cytotoxic molecule, as described in my dissertation, could provide a better solution for the current problems associated with the treatment of thyroid cancer.

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