Cell and Developmental Biology Commons^™

The Development Of A New Water-Soluble Zinc Porphyrin, Zntpp--5ap, For Photodynamic Therapy, Kaylee Johnson

Honors Theses

This research focuses on synthesizing a new water-soluble porphyrin with a zinc core that can be used as a photosensitizing agent in photodynamic therapy. Photodynamic therapy is a process in which light is used to activate a photosensitizer to cause cell death. For this study, the porphyrin was synthesized by adding 5-amino-1-pentanol to the ZnTPPC. Once the porphyrin was synthesized it was purified using column chromatography through Sephadex LH-20 and G-50. The structure of the purified ZnTPP-5AP was then analyzed using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), and ultraviolet-visible spectroscopy (UV-vis). Purity of the ZnTPP-5AP was tested using …

Developing Zntpp-4ab As A Potential Photodynamic Therapy Agent, Kennedy Johnson

Honors Theses

Photodynamic therapy is a fairly new technique used in cancer treatment involving the use of a photosensitizer and light exposure to kill malignant cells. In this research, the use of ZnTPP-4AB as a photosensitizer and red light as a source of radiant light energy was explored in terms of cytotoxicity in the A549 lung cancer cell line. ZnTPP-4AB was synthesized by replacing the carbonyl functional groups on the ZnTPPC porphyrin with 4-amino-1-butanol. Following synthesis, the new porphyrin was purified through the use of Sephadex LH-20 and G-50 in column chromatography in order to remove impurities. To confirm the identity and …

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.

Purification Of Pcbp2 And Its Effect On The Formation Of Dna I-Motifs And Secondary Structures, Nathan Redden

Honors Theses

Several secondary, non-B forms of DNA are associated with the promoter regions of many oncogenes, including the intensely studied c-MYC gene that codes for a transcription factor. Two such secondary structures, G-quadruplexes, and i-motifs, have become topics of interest due to their prevalence within oncogenic promoters, as well as their potential accessibility for drug targeting. B-form DNA can adopt alternative structures under certain conditions. These alternative structures are favored when there is an asymmetric distribution of guanosine and cytosine on complimentary DNA strands. The strand rich in guanosine is able to form a quadruple stranded DNA complex termed a G-quadruplex. …

Defying The Darkness: Countering Cancer With Light, Travis Hankins

Honors Theses

Triple-Negative Breast Cancer (TNBC) accounts for upwards of 15% of reported breast cancer cases. This subtype of breast cancer poses a greater threat to those diagnosed as compared to other types of breast cancer due to the lack of treatment options available. Additionally, TNBC grows and spreads faster, tends to be more aggressive, and has a greater chance of recurrence than its counterparts. Altogether, TNBC cases generally have a worse prognosis over other types of breast cancer. Photodynamic therapy (PDT) is currently being researched as a way to treat TNBC. Photodynamic therapy agents are light-activated materials used for localized disease …

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 …

A Mathematical Model Of Pancreatic Cancer Growth And Response To Treatment, Allison Cruikshank

Honors Theses

Pancreatic cancer is one of the leading causes of death due to cancer in the United States. Analyzing the effects of radiation is extremely valuable in determining when a patient is allowed surgical resection, which is, presently, the only potentially curative treatment for pancreatic cancer. This study examines pancreatic tumor growth and shrinkage to predict tumor response and change of resectability for pancreatic cancer patients undergoing radiation therapy. This is done using ordinary differential equations as a mathematical model. Mathematical models have increasingly been applied to various biological systems/processes to analyze the principles involved. In our project, a population dynamical …

Breast Cancer Sub-Clones That Metastasize To Lung And Bone Exhibit Different Metabolic Preferences, Mollie Merrell

Honors Theses

Metastasis is responsible for the majority of cancer related deaths. In breast cancer the lungs and bones are the major sites for metastasis. Previous studies used the metastatic aggressive MDA-MB-231 breast cancer line to isolate sub-clones that preferentially invade the lungs (LM line) or bones (BoM line). While genes associated with the tissue specific metastasis have been identified, it is unknown if metabolic adaptations contribute to the growth of the LM and BoM lines in their respective organs. The goal of this study was to test the hypothesis that the LM and BoM lines exhibit differences in glucose and glutamine …

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 …

Cell Proliferation And Viability Inhibition By Resveratrol On Breast Cancer Cell Lines, Kyle Ford Gordon Jr

Honors Theses

Antioxidants are well-known for their various health benefits. They are able to protect cells from being damaged by free radicals that are produced by vital biochemical processes. It has long been known that antioxidants are important in our everyday health, but their potential as disease preventers and potential therapeutic agents is a relatively new field of study. Resveratrol, a natural polyphenol and well-known antioxidant, is found in plants, fruits, and products derived from them, like red wine. Resveratrol has been shown to have various properties, including antiaging, anti-aggregation of platelets, anti-inflammatory, and anticancer activities. Because of their many health benefits, …

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. …

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, …

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 …

Using Light To Kill Cancer: Development Of A Novel Photodynamic Therapy, Alicia Hamilton Moore

Honors Theses

Photodynamic therapy (PDT) is a treatment that uses special drugs called photosensitizing agents along with light to kill cancer cells. The specialized drugs only work after they have been activated or "turned on" by light. Photodynamic therapy may also be called photoradiation therapy, phototherapy, or photochemotherapy. In this research, I focused on the addition of four separate hydroxyl-amines to the unsubstituted porphyrin core, H₂TPPC. The hydroxyl-amines attached to the porphyrin core were 5- amino-1-pentanol, 2-amino-2-ethyl-1, 3-propanediol, 3-amino-propanediol, and 5-aminovaleric acid. The novel water soluble PDT agents, H₂TPP-A50H, H₂TPP-2ET, H₂TPP-3NH, and H_{2 …}

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. …

Killing Cancer With Light, Kaitlyn Thomas

Honors Theses

Photodynamic therapy (PDT) is a relatively new treatment option in medicine including treating some types of cancers. PDT utilizes light to activate small molecules for treatment. Some of these molecules used as PDT agents are porphyrin derivatives. While PDT is currently being used in the fight against cancer, it has several limitations and is currently being used in conjunction with chemotherapy and/or radiation in order to be effective. This research focused on synthesizing a new zinc (II) porphyrin and incorporating a fluorescent sulfocycline and testing the compound on the MB 231 breast cancer cell line.

Once the metallated porphyrin was …

Drosophila Models To Investigate The Role Of Regulation Of Cell Death In Development And Cancer, Anam Hussain

Honors Theses

Cell death is of key importance in maintaining health and normal development. In cancer, cell death is improperly controlled provoking uncontrolled proliferation of cells, which results in severe harm to the body. The Hippo pathway is an identified pathway in Drosophila melanogaster that is involved with regulating the different mechanisms of survival and proliferation within the cells. It is known to interact with a gene known as Dronc that is a key participant in the cell death pathway of apoptosis. Previous work has shown how the loss of certain caspases, which are cysteine proteases, is linked with cell survival. My …

Caring For Cancer, Jason Monroe Stevenson

Honors Theses

"Your child has cancer" are words that no parent wants to hear, and no physician wants to speak. However, approximately 1 in 10,000 children each year will receive this unfortunate news (Society). Another unsettling statistic is that a number of families will be hearing these unsettling words in a less than appropriate fashion, such as brief phone calls, voicemails, and unsympathetic consultations....

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 …

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 …

Oral Cancer Screening, Damon Omar Watson

Honors Theses

Cancers of the oral cavity and pharynx have increased throughout the decades. Since oral cancer represents a small percentage of the total cancers in the United States, it is often overlooked. Though this is the case, the results of this cancer can be devastating. To address this issue, an Oral Cancer Screening was organized on August 14, 1996 at the West Michigan Cancer Center in Kalamazoo. This was a joint collaboration between the author, the West Michigan Cancer Center, and the Kalamazoo Valley Dental Society. This event allowed research to take place concerning the data obtained. Confidential results and information …