Date of Award

8-2014

Degree Type

Thesis

Degree Name

Master of Science

Department

Biology

Program

Biology

First Advisor/Chairperson

Dr. Robert Winn

Second Advisor

Dr. Robert Belton

Third Advisor

Dr. Johnathan Lawrence

Fourth Advisor

Dr. Richard Rovin

Abstract

Glioblastoma is one of the most difficult cancers to treat because it is aggressive and resistant to therapy. The discovery of new therapeutic targets is drastically needed as zero improved treatment options have been added to the standard of care over the past 15 years. New and promising therapeutic targets are arising from psychosocial and environmental enrichment studies examining the role of stress in cancer progression. In animal models, eustress appears to slow tumor growth and recurrence resulting in increased overall survival and progression free survival while distress is associated with decreased overall survival. The cellular pathways activated by eustress were examined in glioblastoma cell lines; leading us to examine the use of β3 adrenergic stimulation to decrease leptin gene expression as a possible novel therapeutic. The role of leptin and β3 adrenergic stimulation were examined using a cell viability assay to assess changes in proliferation and quantitative PCR to assess gene expression. With the use of a selective β3 agonist, leptin and leptin receptor mRNA was down regulated and resulted in decreased cell proliferation. Leptin’s observed role in glioblastoma cell proliferation and survival was supported by treatments with a leptin antagonist, resulting in decreased cellular proliferation. This evidence would suggest further examination of leptin as a therapeutic target for glioblastoma.

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