Medicine and Health Sciences Commons^™

Design, Synthesis And Evaluation Of Novel Inhibitors Of Type 5 And 10 17Β-Hydroxysteroid Dehydrogenases, Ahmed Morsy

Theses & Dissertations

17β-Hydroxysteroid dehydrogenases (17β-HSDs) are essential enzymes in steroid metabolism. More and more evidence points to the pivotal contributions of these enzymes in various other metabolic pathways. Therefore, the latest research results give new insights into the complex metabolic interconnectivity of the 17β-HSDs with human diseases. This dissertation focuses on the metabolic activities of type 5 and 10 17β-HSDs. More specifically, regarding 17β-HSD5 contributions to the progression of prostate cancer (PCa) and 17β-HSD10 aggravation of amyloid-beta (Aβ)-induced toxicity in Alzheimer's disease (AD).

The second leading cause of cancer-related death in males is PCa, with the highest incidence rate of all cancers …

Smart Delivery Of Genes And Drugs For Treatment Of Cancer, Feng Lin

Theses & Dissertations

The ineffective delivery of genes and drugs have become a big obstacle for the treatment of cancer, due to either poor stability or low aqueous solubility. In the first part, A ROS responsive polymer named poly(ethylene glycol)–poly[aspartamidoethyl(p-boronobenzyl)diethylammonium bromide] (PEG-B-PAEBEA) was developed for codelivery miR-34a mimic and small molecule PLK1 inhibitor volasertib (BI6727) for the treatment of pancreatic ductal adenocarcinoma (PDAC), since tumor suppressor microRNA-34a (miR-34a), which targets many oncogenes related to proliferation, apoptosis, and invasion is significant downregulated while Polo-like kinase 1 (PLK1) closely associated with short survival rates of pancreatic cancer patients is remarkably upregulated . In part 2, …

Development Of Approaches Of Tumor Trapping Enhanced Bb2r-Targeted Radiopharmaceuticals For Prostate Cancer, Wenting Zhang

Theses & Dissertations

The Gastrin-Releasing Peptide Receptor (BB2r) has been intensively investigated as a cancer target over the years. Numerous diagnostic and therapeutic BB2r-targeted agents have been developed for various solid tumors, including prostate cancers, due to the high expression level of BB2r on neoplastic relative to normal tissues. The development of those targeted agents have mainly utilized the modified c-terminal of bombesin(BBN), a peptide that has nanomolar binding affinity to human BB2r. However, a major issue that hinders the clinical translational potential of low-molecular weight, receptor-targted agents, is their short residence time at tumor tissues due to the intrinsically high diffusion and …

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 …

Development Of Hypoxia Trapping Enhanced Bb2r-Targeted Radiopharmaceutics For Prostate Cancer, Zhengyuan Zhou

Theses & Dissertations

The Gastrin-Releasing Peptide Receptor (BB2r) has been investigated as a diagnostic and therapeutic target for prostate and other cancers due to the high expression level on neoplastic relative to normal tissues. A variety of BB2r-targeted agents have been developed utilizing the bombesin(BBN) peptide, which has shown nanomolar binding affinity to human BB2r. However, as with most of the low-molecular weight, receptor-targeted drugs, a major challenge to clinical translation of BB2r-targeted agents is the low retention at the tumor site due to intrinsically high diffusion and efflux rates. Our laboratory seeks to address this deficiency by developing synthetic approaches to selectively …