Medicine and Health Sciences Commons^™

Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru

Dissertations & Theses (Open Access)

Less that 10% of pancreatic cancer patients are eligible for curative resection, and clinical trials evaluating chemoradiation in locally advanced patients with unresectable disease have been largely disappointing. New and creative therapeutic approaches are needed to address the unment need for treatment options. The objective of this thesis is to advance radiosensitization of treatment-resistant densely desmoplastic pancreatic cancer using nanoparticles to surmount biological barriers to effective particle distribution for DNA-targeting.

Clinical translation of radiosensitizing nanoparticles has stalled owing to technical challenges. Current strategies to use AuNPs for radiosensitization require large quantities of gold, kilovoltage x-rays, immediate irradiation after intravenous administration, …

A Context-Forward In Vivo Functional Genomics Platform For Target Discovery And Establishing Vulnerability Context In Pancreatic Cancer, Johnathon Rose, Johnathon Lynn Rose

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a very poor patient prognosis (5-year survival of ≤ 7%). While transcriptional profiling has aided in the classification of this disease into at least two broader subtypes, this alone has so far been insufficient to inform on more nuanced patterns of oncogenic dependency. We hypothesized that a more comprehensive and granular characterization of PDAC disease diversity is required to establish relevant context for targeted therapy. To this end, we sought to establish an integrated platform to: i) more comprehensively characterize differential oncogenic signaling across our tumor models, and ii) establish …

Investigating The Role Of Oncogene C-Terminal Binding Protein (Ctbp) In Pancreatic Ductal Adenocarcinoma, Kranthi Kumar Chougoni

Theses and Dissertations

The transcriptional coregulator CtBP2 has been implicated as an oncogene in colon, prostate, breast and ovarian cancers. Previously, we reported overexpression of CtBP2 in human PDAC specimens. However, its exact role in PDAC is still unclear. In the current study, we attempt to delineate the oncogenic role CtBP2 in PDAC growth and metastasis. Using an orthotopic syngeneic pancreatic tumor mouse model (CKP), we found that deletion of Ctbp2 decreases PDAC tumor growth, proliferation, metastasis, EMT and significantly prolongs survival. Further, we identified significant downregulation of Erbb3 mRNA levels upon deletion of Ctbp2 in CKP PDAC cells As ErbB3 signaling was …