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Developing Novel Water-Soluble Porphyrins For Potential Use As Photosensitizers In Photodynamic Therapy, Kayla R. Whittington

Honors Theses

Photodynamic therapy (PDT) is a treatment modality for various illnesses, including some types of cancer. Lung cancer is the leading cause of cancer death in the United States. The prevalence of lung cancer in certain gender, racial, ethnic, and socioeconomic groups add to existing health disparities in the United States. For this reason, it is necessary to address the social determinants underlying lung cancer disparities, as well as improve treatment options. These treatment options should be cost effective, convenient, and increase survival rates. This research focused on synthesizing novel water-soluble porphyrin compounds for use as photosensitive agents in PDT for …

Analysis Of Invasion Proteins Mmp2, Mmp9, Adam12, And Adam17 In Glioblastoma U87mg Cells Treated With Anti-Cancer Compound 3,4-Dimethoxybenzaldehyde, Andras Muranyi

Honors Theses

This research tested the effectiveness of novel compound 3,4-dimethoxybenzaldehyde, demonstrated to have anti-cancer properties. U87MG Glioblastoma cells were exposed to the compound at its LC50 concentration, then processed to collect proteins from the cells. Proteins were analyzed via Western blotting for specific protein levels of matrix metalloproteinase 2 and 9 (MMP) and disintegrin and metalloprotease 12 and 17 (ADAM). Previous research indicates these proteins are involved in the invasive properties of glioblastoma cells. Westerns were quantified with ImageJ and compared using a one-way ANOVA. Results indicate the compound has minimal effect upon the expression of MMP2, MMP9, ADAM12, ADAM17 proteins.

Analyzing The Effects Of E-Hook Peptides On Kinesin-1, Ashton Ward Murrah, Baylee Hope Howard

Honors Theses

Cancer is the second leading cause of death in the United States. Cancerous growth is a result of oncogenes, or mutated genes that increase the rate of cell division in an uncontrolled manner. Cell division, which consists of mitosis and cytokinesis phases, is dependent upon the active movement of kinesin motor proteins along microtubules to rearrange the cytoskeleton for equitable distribution of genetic material to daughter cells. As kinesins are vital to this process, if we could prevent kinesin from binding to the microtubules, cell division would cease.

The goal of this study is to develop a method to prevent …

Honokoil Treatment On Glioblastoma Cells, Julianne Weaver

Honors Theses

Glioblastoma is a malignant brain tumor without effective treatment options available because of its resistance to chemotherapy and radiation. This specific type of cancer is difficult to treat because the cancer stem cells that are not actively growing. These cells are dormant, which means they will not react to treatment because they are not dividing, and it is these cells that result in the high prevalence of relapse. Honokiol is a Chinese magnolia species that is known for its anti-inflammatory, anti-proliferative, and proapoptotic effects which make it an optimal candidate for glioma cell treatment. Honokiol was used in this experiment …

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …

Glucose Metabolism Of Breast Cancer Sub-Clones That Preferentially Metastasize To The Lungs And Bone, Anna G. Skubiz

Honors Theses

Malignant breast cancers exhibit preferential metastasis to bone and lung (1). While changes in gene expression in lung-specific (LM) and bone-specific metastasis (BoM) lines derived from the MDA-MB-231 breast cancer line have been identified, few metabolic genes are differentially expressed; thus it is unknown if tissue-specific metabolic reprogramming occurs. Two hallmarks of cancer cells are an altered metabolic phenotype characterized by enhanced conversion of glucose to lactate in spite of adequate oxygen availability for complete mitochondrial oxidation of this substrate (referred to as aerobic glycolysis or the Warburg effect) and a greater dependence on glutamine. These changes in primary tumor …

Synthesis Of An Arylidene Pyrazolone And Its Effects On Glioblastoma Cancer Cells, Joanna Deonarine

Honors Theses

The purpose of this research is to develop a new technique to synthesize a heterocyclic arylidene compound using fruit puree catalysis and investigate its anti-cancer activity on glioblastoma cancer cells. Recently, there has been interest in heterocycles due to their anticancer properties and they have been used in almost two-thirds of the novel molecular anticancer agents. Varying fruit purees were used to synthesize a novel hybrid arylidene pyrazolone from 3-methyl-1-phenyl-5-pyrazolone and 4-dimethylaminobenzaldehyde by modifying methodology developed by Dr. Murray. This arylidene pyrazolone was then tested for its anticancer activity on glioblastoma brain cancer cells using Dr. Smith’s 12-well cell viability …

Developing A New Water-Soluble Porphyrin As A Potential Photodynamic Cancer Therapy Agent, Catherine Shirley

Honors Theses

Photodynamic cancer therapy (PDT) is a type of treatment involving the use of light in conjunction with a photosensitive agent- a chemical or series of chemicals designed for activation when exposed to light. This research project investigated the synthesis and identification of the novel photosensitive agent, H2TPP-Pro-OH. To create the water-soluble porphyrin, (S)-(+)-prolinol was reacted with the tetra-carboxyl porphyrin, H2TPPC, to form the final H2TPP-Pro-OH product. This compound was then purified using syringe filtration and column chromatography, and subsequently characterized using infrared (IR), nuclear magnetic resonance (NMR), and Ultraviolet-visible (UV-vis) spectroscopies, as well as High Performance Liquid Chromatography (HPLC). Finally, …

Preparation And Cytotoxicity Of Novel Carbon Nano-Onion Materials, Cammie York

Honors Theses

The applications of carbon nanomaterials (CNM), including graphene and its derivatives such as carbon nanotubes (CNTs) in nanomedicine is well established. These nanomaterials have been widely used as theranostic delivery systems with the potential to deliver bioactive agents and simultaneously detect selectively diseased tissues. A rather underexplored CNM for biomedical imaging and theranostics delivery are carbon nano-onions (CNOs). CNOs are carbon-based nanomaterials that can potentially be used in cancer therapy when they are functionalized. Recent studies on cellular fate of different CNMs, including CNOs, have demonstrated that the surface composition is critical for the in vivo application of these CNM. …

Assay Development For Isolation And Characterization Of Anticancer Properties Of Marine Fungi, Kyra Ricci

Honors Theses

Metabolites from fungi have potential use in the drug discovery process and have been used in the past to develop therapeutic agents for human use. Initial characterization of potential therapeutic properties of fungi is thus an important first step in identifying novel therapeutic compounds. In the present study, marine fungi were isolated from Myrtle Beach and assayed for anticancer properties using the soft agar colony formation assay in a 3D in vitro cellular environment. Many species were isolated from environmental samples, displaying unique morphologies and growth patterns. To optimize the soft agar assay in a six-well cell culture plate for …

Effectiveness And Mechanism Of Action Of Modified Porphyrins For Photodynamic Therapy Of Triple Negative Breast Cancer Cells, Hannah Brandon

Honors Theses

Triple negative breast cancer (TNBC) is a particularly aggressive form of breast cancer that lacks the three molecules typically targeted for treatment. Standard treatment methods leave much to be desired--the rates of metastasis and recurrence are high and the prognosis for most patients with TNBC is poor. One potential treatment for TNBC is photodynamic therapy (PDT), which uses compounds called photosensitizers that are taken up by all tissues in the body. The tumor is exposed to light, activating the photosensitizer and creating reactive oxygen species that cause cell death. This method is relatively pain-free, effective, and does not harm cells …

Killing Breast Cancer One Porphyrin At A Time, Taylor C. Lymburner

Honors Theses

New treatments for cancer are continuously being developed and improved. One such treatment is Photodynamic Therapy, more commonly referred to as PDT. PDT is quickly becoming more popular due to its relative lack of side effects that are present in other treatments. In PDT, light-sensitive agents are required and are activated by light in the targeted cells. There are many types of PDT agents but the one focused on in this research is a four-pyrrole ring structure known as a porphyrin. The combination of H2 TPPC with 3- amino-oxetane-3-yl-methanol created the final product ofH2TPP-Oxo-MeOH. Once the porphyrin was formed, it …

Effectiveness And Mechanism Of Action Of Modified Porphyrins For Photodynamic Therapy Of Triple Negative Breast Cancer Cells, Alex Abbott

Honors Theses

Triple negative breast cancer is an aggressive family of cancers that are extremely difficult to treat. Therefore, the prognosis for most patients with TNBC is poor. The goal of this research is to determine if photodynamic therapy could be a possible option for TNBC in the future using MDA-MB231 cells. MDA-MB231 cells were originally isolated from a patient with triple negative breast cancer and have been used for many studies, so they would work well for this study. Photodynamic therapy uses compounds called photosensitizing agents which are taken up by all tissues in the body and then activated by light. …

Polychlorinated Biphenyl (Pcb) Pollution Of The Hudson River: Social Policy And Health Considerations, Laura Schad

Honors Theses

The purpose of this paper is to examine pollution in the Hudson River and the role General Electric has had in creating this problem. The focus will be on social issues and problems that have emerged as a result of the environmental damage from pollution. Until recently, there was little research done on the health and environmental justice issues that impact the New York communities where GE’s factories were located. This paper examines the material collected and studies that were done which document Hudson River pollution and the contributions as well as cleanup efforts of General Electric. The overall problems …

Investigating The Mechanism Behind The Cytotoxic Effects Of Ajulemic Acid (Aja) On Ewing's Sarcoma By Employing Smap And Sybyl-X1.3 Surflex Dock Software Programs To Find Receptors For Aja, Rebekah Ward

Honors Theses

Ewing's Sarcoma (ES) is a malignant cancer characterized by the formation of tumors in bones or soft tissues of primarily children and young adults. With the tendency for local recurrence and metastasis, ES is an aggressive cancer. The treatment is intensive and often yields poor long-term results. A cannabinoid derived compound, ajulemic acid (AJA), has shown strong cytotoxic effects on ES cell lines. The synthetic compound is unlike its cannabinoid counterpart tetrahydrocannabinol by lacking psychotropic effects. To investigate the possibility of utilizing AJA as a chemotherapeutic drug, the biochemical mechanism behind the cytotoxic effects of AJA needs further research. A …

Targeted Delivery Of Ribonucleotide Reductase Sirna In Cancer Cells Via Gold Nanoplexes, John Caleb Grenn

Honors Theses

Cancer treatment has much room for improvement, as therapies today cannot differentiate well between what cells are part of a tumor and which are healthy. Our research involves targeting cancer cells by their overexpressed folic acid receptors, and delivering small interfering RNAs (siRNAs) to silence genes crucial to cell survival by the RNA interference gene knockdown pathway. By using Gaussia luciferase siRNA (siGLuc) as a model for cell delivery, we have been able to test our ability to deliver siRNA via a gold nanoparticle delivery system, also developed in our lab. We also synthesized ribonucleotide reductase siRNA (siRRM2), which will …

The Characterization Of Aunp-Pei Conjugates For Sirna Delivery To Cancer Cells, Albert J. Nosser

Honors Theses

Cancer is one of the leading causes of death for people in the United States. Despite the numerous cancer treatments available, many of these chemotherapy treatments cause negative side effects such as hair and weight loss. With this in mind, in the past 15 years, researchers have discovered a mechanism known as RNA interference, which can be used to control certain genes and their activity. This mechanism is based on the function of siRNA molecules, which can be inserted into cells.(12) These siRNA molecules can be manipulated to target and eliminate specific cancer cells. However, these siRNA molecules are normally …

Using Spheroids And A Bioluminescent Mouse Model To Determine The Effects Of Ajulemic Acid On Ewing's Scarcoma, Drake Hardy

Honors Theses

Ewing's Sarcoma is a pediatric bone cancer with a five-year survival rate of only 30%. New treatment options for this highly aggressive disease are desperately needed. Ajulemic acid (AJA), a synthetic cannabinoid, has been the focus of our research, and has demonstratedd the ability to decrease tumor cell viability and inhibit endothelial cell migration and angiogenesis. Based on these results, AJA is a potential therapeutic agent for Ewing's Sarcoma and other solid pediatric cancers. In order to create a realistic environment in vitro in which to study these tumors, we created 3-dimensional spheroids with three cell types, each of which …