Medicine and Health Sciences Commons^™

Photodynamic Therapy Agents: The Power Of Mjöllnir To Eradicate Cancer, Sidney M. Hopper

Honors College Theses

After its discovery back in the 1900s, photosensitizers became a critical study for potential treatments and cures for medical issues, including cancer. It was discovered that porphyrins appeared to target and accumulate in proliferating cells, and to reach the cells, a certain wavelength of light with maximum absorbance associated with the porphyrin was necessary to achieve cell death. Photodynamic therapy involves making use of porphyrins or metalloporphyrins as activators when exposed to such light. When activated, these compounds generate reactive oxygen species (ROS), such as HO- or O2-, which can react with nucleic acids found in DNA and RNA. In …

Characterizing The Role Of Tdg In Fxr-Dependent Signaling, Oladapo A. Onabote

Electronic Thesis and Dissertation Repository

Thymine DNA Glycosylase (TDG) plays a key role in active demethylation by excising intermediates of 5-methylcytosine. The function of TDG is required for embryonic development, as Tdg-null embryos die at E11.5. To bypass this embryonic lethality, our lab generated conditional Tdg knockout (TDG_CKO) mice. These mice develop late-onset hepatocellular carcinoma (HCC), partly due to impaired Farnesoid X Receptor (FXR) signaling. Interestingly, Fxr-knockout mice display a similar phenotype and transcriptional profile to TDG_CKO mice, prompting us to investigate a role for TDG in FXR signaling. To this end, we generated Tdg/Fxr double-knockout (DKO) mice. …

Metabolic Regulation Of Cellular Signaling, Rashid John Darbandi

Theses and Dissertations (ETD)

Using the biochemically tractable Xenopus oocyte model system, we have previously characterized a novel metabolic regulation of cell death. We found that glucose-6-phosphate (G6P) via the pentose phosphate pathway leads to increased nicotinamide adenine dinucleotide phosphate (NADPH) levels, a subsequent increase in cytosolic acetyl-coenzyme A and activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). We recently identified coenzyme A (CoA), derived from the breakdown of acetyl-CoA, as the key metabolic signal that mediates a novel mechanism of calmodulindependent activation of CaMKII. CoA binds directly to the calmodulin (CaM) binding domain (CaMBD) of CaMKII resulting in its activation and downstream inhibitory phosphorylation …

The Discovery Of A Novel, Ras-Mediated Nore1a/Pmliv Tumor Suppressor Complex., Jessica Mezzanotte Sharpe

Electronic Theses and Dissertations

Ras is the most commonly activated oncogene in human cancer. Activated Ras drives cell growth and proliferation by activating multiple mitogenic signaling pathways. However, Ras also has the paradoxical ability to promote anti-growth, pro-apoptotic, and pro-senescent signaling. The signaling pathways of many of these biological effectors remain poorly defined. One group of proteins capable of promoting Ras-induced apoptosis and cell cycle arrest is the RASSF family of tumor suppressors. Novel Ras Effector 1A, or NORE1A, was the first member of this family discovered and is a bona fide tumor suppressor that is lost or inactivated in a number of different …

Synthesis And Characterization Of Nanoparticle-Coupled Proteins In Human Serum Albumin, Kyle M. Mahoney

Honors College Theses

Recently, cancer has become an ever-growing issue and has led to many researchers attempt to unravel the mystery of the disease. This research has led to a promising field of treatment: nanotechnology-coupled pharmaceuticals. Nanoparticles act as a whole unit when in conjugation with other molecules and add to the carrier molecule, most often proteins, benefits the nanoparticles themselves possess. One such carrier protein that can be conjugated with nanoparticles is Human Serum Albumin (HSA). Albumin is of interest in cancer research for two reasons: it is native to the human vasculature so it does not elicit immunological reactions, and it …

Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad

Theses and Dissertations

Glioblastoma multiforme (GBM) is the most common primary brain tumor. Studies have shown that targeting the DNA damage response can sensitize cancer cells to DNA damaging agents. Ataxia telangiectasia mutated (ATM) is involved in signaling DNA double strand breaks. Our group has previously shown that ATM inhibitors (ATMi) sensitize GBM cells and tumors to ionizing radiation. This effect is greater when the tumor suppressor p53 is mutated.

The goals of this work include validation of a new ATM inhibitor, AZ32, and elucidation of how ATMi and p53 status interact to promote cell death after radiation. We propose that ATMi and …

Novel Insights Into The Role Of The Smoothened Cysteine Rich Domain In Hedgehog Signalling, Rajashree Rana

Theses and Dissertations (ETD)

The Hedgehog (Hh) signal transduction pathway functions as one of the key developmental pathways and deranged Hh signalling is associated with numerous cancer and tumor conditions. The Smoothened (Smo) G protein coupled receptor (GPCR) functions as the signal transducer of the Hh pathway and is the most attractive drug target of the pathway. The structure of the Smo receptor includes seven membrane spanning domains, extracellular and intracellular loops connecting the membranous domains and the extracellular cysteine rich domain (CRD). The extracellular CRD of the Smo receptor is homologous to the Frizzled (FzD) CRD. The FzD CRD interacts with the physiological …

Nanomaterials And Block Copolymers For Overcoming Multidrug Resistance In Cancer, Wesley Livingstone

Loma Linda University Electronic Theses, Dissertations & Projects

The development of multidrug resistance in cancer is one of the leading causes for decreased chemotherapy efficacy and is particularly threatening to aggressive cancers such as that of the pancreas. In cancers where chemotherapy is amongst the few treatment options, it is crucial to develop chemotherapeutics that either bypass or control the development of multidrug resistance. Polymeric nanomaterials such as Pluronics® are of current interest due to their ability to perform these functions in addition to enhancing pro-apoptotic mechanisms. Using the respectively known chemosensitive and chemoresistant pancreatic adenocarcinoma cell lines MiaPaCa-2 and PANC-1, an in vitro analysis of the synergistic …