Dissertations, Theses, and Capstone Projects

Date of Degree

9-2023

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biochemistry

Advisor

Probal Banerjee

Committee Members

Joel Friedman

Qiao-Sheng Hu

Mohammed Junaid

Khosrow Kashfi

Keywords

Glioblastoma Multiforme (GBM), Curcumin, ATP-Binding Cassette (ABC) Transporters, Methotrexate

Abstract

As the tenth leading cause of cancer death in the United States with a 6.8% five-year survival rate, glioblastoma multiforme (GBM) is a very deadly disease with a poor prognosis. Therefore, a curative treatment is in high demand. Among the widely used anti-metabolites (Chemotherapeutic agents, CAs), each compound approved for human use by the Food and Drug Administration (FDA) has side effects. Three main phenomena contribute to the side effects and the reappearance of cancer: (a) the cancer cells become resistant to chemo- and radiation therapy; (b) this chemo-resistance prompts the use of higher doses of the chemotherapeutic agents; and (c) the higher doses of the CAs also kills the proliferating immune cells, thereby causing immune-suppression and associated infections that often kill the patients. Amid such mixed success, a latent question has remained, “Could we invent an effective but simple strategy of turning at least some of the chemotherapeutic agents into side effect-free anti-metabolites that could bring about long-term cancer remission?” Our earlier publications targeted curcumin (CC) to antibodies, an approach that killed melanoma and glioblastoma brain cancer cells. In the current study, we developed methods for brain cancer cell implantation, immunohistochemistry of the tumor tissue, and tumor-cell dispersion for flow cytometry to help study curcumin-mediated repolarization of TAMs and recruitment of NK cells to eliminate GBM. Additionally, we attempted to develop CA-CC adducts to achieve repolarization of TAMs and eliminate chemoresistance in the GBM cells.

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