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Targeted Inhibition Of Pi3k, Mtor, And Igf1r For The Treatment Of Undifferentiated Pleomorphic Sarcoma, Caitlin Denise May

Dissertations & Theses (Open Access)

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal malignancy largely devoid of indicators for its originating tissue. Surgery remains the standard of care, as radiation therapy and systemic chemotherapy have limited efficacy in UPS patients with localized and metastatic disease, respectively. Therefore, it is imperative to identify and evaluate novel therapeutic targets in UPS in order to provide more efficacious treatment options for patients. Previous studies have revealed that members of the phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway can be used to predict patient outcome in cohorts containing patients with various subtypes of soft tissue sarcoma. Furthermore, we have …

Isoform Selective Regulation Of Adenylyl Cyclase By Small Molecule Inhibitors And Gbetagamma Protein, Cameron S. Brand

Dissertations & Theses (Open Access)

The nine membrane-bound isoforms of adenylyl cyclase (AC), via synthesis of the signaling molecule cyclic AMP (cAMP), are involved in many isoform specific physiological functions. All nine isoforms share a similar structural organization; thus, AC isoform differences in physiological function are due to different regulatory profiles. A physiological example is Gβγ, which can conditionally enhance stimulation of ACs 2, 4, 5, 6, and 7, but inhibit ACs 1, 3, and 8. There is also pharmacological control of AC isoforms through small molecule inhibitors.

Isoform specific AC functions could be explained by regulatory differences as subtle as single amino acid changes. …