Medicine and Health Sciences Commons^™

Sprtn Metalloprotease As A Target To Sensitize Cancer Cells To Crosslinking Chemotherapy, Cole J. Turner

Honors Theses

Bifunctional alkylating agents have demonstrated high clinical utility as a chemotherapeutic strategy against cancer. These compounds have been well-characterized for their capacity to exert cytotoxicity via interstrand DNA crosslinking. However, the same electrophilic chemistry can also form DNA-protein crosslinks (DPCs) whose contributions to these drugs’ antitumor effects have been less well-defined. Recently, the metalloprotease SPRTN has been implicated as a predominant mediator of DPC repair in mammalian cells. Previous work has demonstrated that SPRTN deficiency increases the sensitivity of cancer cells to DPC-inducing agents such as formaldehyde and cisplatin, but these findings have yet to be translated more broadly across …

Retinoids And Their Clinical Benefits To Treating Cutaneous T-Cell Lymphoma, Baker Kendrick

Honors Theses

Cutaneous T-Cell Lymphoma (CTCL) is a deadly form on non-Hodgkin lymphoma that primarily affects the skin. Non-Hodgkin lymphoma means that the lymphoma does not have the presence of Reed-Sternberg lymphocytes. A lymphoma, also known as lymphatic cancer, affects the lymphoid tissues, which plays a major role in the immune system. Lymphoid organs include the lymph nodes, thymus, spleen, and bone marrow. Lymphatic fluid, also known as lymph, travels through the bloodstream to transport lymphocytes, a type of white blood cell, to and from lymphatic organs. Due to a high concentration of lymphocytes in the skin, lymphoma primarily affects cutaneous areas. …

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …

Fluorescent Probe Development For Fructose Specific Transporters In Cancer, Joseph Fedie

Dissertations, Master's Theses and Master's Reports

Carbohydrate transporters or GLUTs of the major facilitator superfamily (MFS) are responsible for transporting sugars into the cell and have been of research interest for decades. Disruptions, mutations, and over-activations of GLUTs have been linked to a number of major diseases including cancer, obesity, and diabetes. Differentiating between transporters is incredibly difficult due to highly conserved structures, and so specific targeting between transporters has proven a complex challenge. GLUTs are highly flexible in their conformations however exactly what will and will not pass through the transporter is ambiguous at best, and many attempt to target these transporters have failed.

In …

Engineering Novel Detection And Treatment Strategies For Bacterial Therapy Of Cancer, Jan T. Panteli

Doctoral Dissertations

Finding and treating cancer is difficult due to limited sensitivity and specificity of current detection and treatment strategies. Many chemotherapeutic drugs are small molecules that are limited by diffusion, making it difficult to reach cancer sites requiring high doses that lead to systemic toxicity and off-target effects. Tomographic detection techniques, like PET, MRI and CT, are good at identifying macroscopic lesions in the body but are limited in their ability to detect microscopic lesions. Biomarker detection strategies are extremely sensitive and able to identify ng/ml concentrations of protein, but are poor at discriminating between healthy and disease state levels due …

Effect Of Chemotherapeutic Treatment Schedule On A Tissue Transport Model, Dan E. Ganz

Masters Theses

Current chemotherapeutic treatment schedule prediction methods rely heavily on PK/PD-based models and overlook the important contribution of tissue-level transport and binding. Tissue-level transport and binding phenomena are essential to understanding drug delivery and efficacy in tumors. Drugs with desirable PK/PD properties often fail in vivo due to poor tissue-level transport. We developed an in silico method to predict the effect of treatment schedule on efficacy that couples PK/PD with tissue-level transport. Treatment schedules were implemented on theoretical drugs with different PK/PD and transport properties. For each drug with a given clearance rate, diffusivity, and binding, treatment schedules consisting of one …

Chitosan/Ellagic Acid Composite Materials For Local Cancer Therapy, Sung Woo Kim

Theses and Dissertations (ETD)

Current advances in the drug delivery have improved the therapeutic efficacy of the drug and minimized risks of side effects associated with toxicity of the drug. Implantable polymeric delivery system has gained increasing attentions for controlled drug release and localized treatments. In comparison to conventional chemotherapy, polymeric delivery systems are implantable at a local targeted site and biodegradable after a sufficient therapeutic span. The objectives of this project were to fabricate and characterize an implantable polymeric vehicle for a local chemotherapy and investigate its biological properties against cancer cells including human WM115 melanoma, human U87 glioblastoma, and rat C6 glioma …