Date of Award

2023-12-01

Degree Name

Doctor of Philosophy

Department

Biological Sciences

Advisor(s)

Renato Aguilera

Abstract

Breast cancer is the second most diagnosed cancer among women and is about 30% of all new cases of female cancers each year. It is projected that 1 in 8 every U.S. woman (about 13%) develop invasive breast cancer over the course of her lifetime. While advances in cancer research have made it possible to elucidate several breast cancer genomic subtypes, and develop new novel therapies, many of these agents are associated with significant toxicity, as well as high costs. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early -stage breast cancer compared to non-users. Substantial evidence supports the use of inexpensive β -AR antagonists against a variety of cancers. Propranolol is a β-AR antagonist (β-Adrenergic Receptor blockers) that has been effectively treating coronary heart disease and high blood pressure since the 1960â??s. Prospective and retrospective data published by our lab and others suggest that non-selective β-AR antagonists are effective at reducing proliferative rates in breast cancers, however the mechanism by which this occurs is largely unknown. The goal of this project was to better understand the molecular pathway and identify molecular markers affected when repurposed drugs such as propranolol are administered to patients with early stage and late-stage breast cancer. The anti-proliferative effects of Propranolol as well as PND was measured in a panel of breast cancer lines cancer cells, which include the highly aggressive MDA-MB-231, MDA-MB-468, MCF-7, and HCC70 cells, to evaluate synergistic activity, but the results indicated no synergistic activity was found and in one cell line showed antagonistic effects.

Language

en

Provenance

Recieved from ProQuest

File Size

78 p.

File Format

application/pdf

Rights Holder

Alexa Noel Montoya

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