Medicine and Health Sciences Commons^™

Novel Therapeutic Strategies For Treatment Of Castration-Resistant Prostate Cancer, Matthew A. Ingersoll

Theses & Dissertations

Prostate cancer (PCa) remains the most commonly diagnosed solid tumor and is the third leading cause of cancer-related death in United States men. While androgen deprivation therapy is the current standard-of-care treatment for metastatic PCa, most patients eventually relapse and develop castration-resistant (CR) tumors, for which there is currently no effective treatment. Therefore, synthesis of novel therapeutic agents and identification of alternative target proteins are necessary to improve treatment. Herein, I investigate the efficacy of novel imidazopyridine and statin derivatives as alternative therapeutic compounds. These molecules not only inhibit androgen receptor signaling, but also block activation of the AKT axis, …

Development Of C5ar-Targeted Nanoparticles For Delivery Of Vaccines, Shailendra Bharadwaj Tallapaka Venkata Sesha

Theses & Dissertations

Since the early attempts of Benjamin Jesty at inducing immunity against smallpox and the pioneering work of Edward Jenner, vaccination has been, and continues to remain, the principal method of protection from diseases. However, most of the successful vaccines have been against pathogens that do not have major mechanisms to evade the immune system. So far, many life-threatening diseases like hepatitis C, HIV infection, malaria etc., have been resistant to existing vaccination strategies. Thus, there is an urgent need to develop new vaccination strategies that can generate long-lived protective immunity against such pathogens.

The purpose of this thesis is to …

Development Of Cxcr4 Inhibitors For Topical Treatment Of Psoriasis, Suthida Boonsith

Theses & Dissertations

Psoriasis is a chronic inflammatory skin disease that is often associated with systemic comorbidities and impaired skin barrier function. There are several treatment options including topical treatment with immunosuppressants, phototherapy, and systemic therapies using small molecules and biological agents. However, none of them can be regarded as a perfect solution due to their toxicity during chronic use. Recently, the CXCR4/SDF-1 axis was found to play an important role in the pathogenesis of psoriasis. AMD3100, a small molecule CXCR4 antagonist can selectively bind to CXCR4 and inhibit skin inflammation, reduce angiogenesis and infiltration of inflammatory cells. Unfortunately, AMD3100 can only be …

Delivery Of Small Molecule And Rna For The Treatment Of Type 1 Diabetes And Prostate Cancer, Di Wen

Theses & Dissertations

The aim of this thesis is to develop combination therapy using a small molecule and RNA including siRNA, shRNA, or miRNA inhibitor for the treatment of type 1 diabetes and prostate cancer. New amphiphilic biodegradable polymers capable of co-delivering small hydrophobic molecules and RNAs or human bone marrow-derived mesenchymal stem cell (hBMSC) for co-delivery of an shRNA and a miRNA inhibitor were used as drug delivery platform. The drug delivery properties were evaluated in vitro and in vivo islet transplantation, subcutaneous and orthotopic prostate cancer models.

In Chapter 1, an overview of prostate cancer, the role of miRNA and …

Targeted Delivery Of Drug Combinations Via Nanocarriers For Cancer Treatment, Kruti Soni

Theses & Dissertations

Combination therapy is preferred over monotherapy to treat cancer as it can show better therapeutic outcomes and also delay the onset of resistance by targeting multiple cell-survival pathways in cancer cells. Rationally developed combinations with monoclonal antibodies and small molecule drugs in the form of antibody-drug conjugates or antibody nanoparticle conjugates allow us to take advantage of the cellular targeting of the potent cytotoxic agents, thereby widening the scope for dose reduction while maintaining the required therapeutic response. This can in turn improve patient tolerability by reducing the off target toxicities. For the therapy of ErbB2 positive breast cancer, the …