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- Creators: Barrett, The Honors College
Description
Cancer, a disease which affects many lives, has been the topic of interest for this research. Treatment options are often available to help lessen the effects of the disease and in regards to cutaneous T-cell lymphoma (CTCL), no cure currently exists. An FDA approved drug by the name of Bexarotene has been developed to provide chemotherapeutic effects within CTCL. Bexarotene has also been used in trials of breast cancer, lung cancer, glioblastoma multiforme and various neurodegenerative diseases. Yet the medication often causes serious side effects including hyperthyroidism, raised triglyceride levels and cutaneous toxicity. The focus of this research is to synthesize a hydroxylated analog compound of Bexarotene in efforts to produce a molecule that provides better chemotherapeutic effects while also lessening the various side effects caused. Synthesis of the molecule followed various organic chemistry techniques and reactions to create the final product. Melting point analysis, NMR and other various characterization data helped to confirm the synthesis of the intended molecule. Preliminary bioassay data results of the analog compound showed similar potency to that of Bexarotene. Further testing, however, will be required to determine the full pharmacokinetic profile of the molecule. Future direction of the research focuses on both further testing of the hydroxylated analog as well synthesizing newer analog compounds to find a molecule that can provide the best effects within cutaneous T-cell lymphoma and the various other diseases as well.
ContributorsMinasian, Ani Christina (Author) / Wagner, Carl (Thesis director) / Marshall, Pamela (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Glioblastomas (GBMs) are the most aggressive type of brain tumor. GBMs are known for their aggressive and invasive nature because of their ability to easily grow and spread into the surrounding areas of the brain. The annual incidence rate of GBM is 2 to 3 people per 100,000 people in the United States and Europe, and the median survival for patients with an aggressive GBM is 14.6 months. The standard of care for GBMs follows a protocol of surgery, radiation concurrent with the chemotherapeutic drug, temozolomide (TMZ), followed by the administration of up to 6 cycles of TMZ in an adjuvant setting. The objective of this retrospective study was to compare the clinical responses in a patient cohort from varying amount of adjuvant TMZ cycles. Using patient overall survival, the responses to TMZ cycles were tested within different groupings, and the patient covariates were analyzed. The results from the different analyses indicated that survival success of GBM patients is not solely dependent on the number of TMZ cycles, but that other covariates can also affect survival outcomes.
ContributorsSuri, Yash (Author) / Swanson, Kristin (Thesis director) / Massey, Susan (Committee member) / School of Geographical Sciences and Urban Planning (Contributor) / School for the Science of Health Care Delivery (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Exosomes have been known to secrete an increased amount of miRNA and noncoding genes that are abnormally expressed in various cancer subtypes. Thus, they may be an early marker for pediatric cancer types that are more difficult to diagnosis without invasive techniques, and may also help identify progression of the disease. In the project, six types of pediatric cancer cell lines, along with their extracted exosomes, were analyzed and tested for different monoclonal antibodies through western blot analysis. The genes EWS-FLI1 and FGFR4 were also identified in some cancer cell lines through Reverse-Transcriptase Polymerase Chain Reaction analysis (RT-PCR). The results were indicative of similar protein markers being found in both the originating cells and their corresponding exosomes.
ContributorsKaur Bhinder, Harsimran (Author) / Lake, Douglas (Thesis director) / Azorsa, David (Committee member) / Barrett, The Honors College (Contributor)
Created2017-12
Description
The rate of cancer incidence is a morbid figure. Twenty years ago, 1 in 2 men and 1 in 3 women were predicted to be afflicted by cancer throughout their lifetime (Cancer Facts & Figures- 1998). In 2017, the rate remains the same ("Cancer Statistic Center"). Every year, more people are affected by cancer, which is a physiologically, psychologically, emotionally and socially devastating disease. And yet the language and metaphors we use to describe cancer focus our attention on the "fight" of the heroic individual against the brutal disease or on finding a cure. Despite this narrow rhetoric, there are many meaningful, supportive, and palliative measures designed to substantively and holistically care for cancer patients, beyond their medical treatment. Many of these interventions help the patient feel supported (and less alone in this "battle") by building robust communities. In this thesis, I argue the summer camps for children affected by cancer are meaningful interventions that offer palliative care throughout their treatment by creating support networks with peers going through similar medical procedures. Drawing on anecdotal evidence from three cancer camps and a detailed literature review of a subset of palliative interventions designed to promote well-being, this thesis proposes a new model for a summer camp that focuses on emotional processing emotional expression, positive psychology in order to improve palliative care for cancer patients.
ContributorsPearce, Spencer Taylor (Author) / Miller, April (Thesis director) / Brian, Jennifer (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
After more than 40 years since the signing of the National Cancer Act in 1970, cancer remains a formidable challenge. Cancer is currently the second most common cause of death in the United States, and worldwide cancer cases are projected to rise 50% between 2012 and 2030 [1-2]. While researchers have dramatically expanded our understanding of the biology of cancer, they have also revealed the staggering complexity and difficulty of developing successful treatments for the disease. More complex assays involving three dimensional cell culture offer the potential to model complex interactions, such as those involving the extracellular matrix (ECM), chemical concentration gradients, and the impact of vascularization of a tissue mass. Modern cancer assays thus promise to be both more accurate and more complex than previous models. One promising newly developed type of assay is microfluidics. Microfluidic devices consist of a silicone polymer stamp bonded to a glass slide. The stamp is patterned to produce a network of channels for cell culture. These devices allow manipulation of liquids on a sub-millimeter level, allowing researchers to produce a tightly controlled 3D microenvironment for cell culture. Our lab previously developed a microfluidic device to measure cancer cell invasion in response to a variety of signals and conditions. The small volume associated with microfluidics offers a number of advantages, but simultaneously make it impractical to use certain traditional cell analysis procedures, such as Western Blotting. As a result, measuring protein expression of cells in the microfluidic device was a continuing challenge. In order to expand the utility of microfluidic devices, it was therefore very enticing to develop a means of measuring protein expression inside the device. One possible solution was identified in the technique of In-Cell-Western blotting (ICW). ICW consists of using infrared-fluorescently stained antibodies to stain a protein of interest. This signal is measured using an infrared laser scanner, producing images that can be analyzed to quantitatively measure protein expression. ICW has been well validated in traditional 2D plate culture conditions, but has not been applied in conjunction with microfluidic devices. This project worked to evaluate In-Cell-Western blotting for use in microfluidic devices as a method of quantifying protein expression in situ.
ContributorsKratz, Alexander Franz (Author) / Nikkhah, Mehdi (Thesis director) / Truong, Danh (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The p53 gene functions as a tumor suppressor that inhibits proliferation, regulates apoptosis, DNA repair, and normal cell cycle arrest. Mutation of the p53 gene is linked to be prevalent in 50% of all human cancers. In this paper, we are exploring triple negative breast cancer and the effects of simvastatin on tumor growth and survival. Simvastatin is a drug that is primarily used to treat high cholesterol and heart disease. Simvastatin is unique because it is able to inhibit protein prenylation through regulation of the mevalonate pathway. This makes it a potential targeted drug for therapy against p53 mutant cancer. The mechanism behind this is hypothesized to be correlated to aberrant activation of the Ras pathway. The Ras subfamily functions to transcriptionally regulate cell growth and survival, and will therefore allow for a tumor to thrive if the pathway is continually and abnormally activated. The Ras protein has to be prenylated in order for activation of this pathway to occur, making statin drug treatment a viable option as a cancer treatment. This is because it acts as a regulator of the mevalonate pathway which is upstream of protein prenylation. It is thus vital to understand these pathways at both the gene and protein level in different p53 mutants to further understand if simvastatin is indeed a drug with anti-cancer properties and can be used to target cancers with p53 mutation. The goal of this project is to study the biochemistry behind the mutation of p53's sensitivity to statin. With this information we can create a possible signature for those who could benefit from Simvastatin drug treatment as a possible targeted treatment for p53 mutant cancers.
ContributorsGrewal, Harneet (Co-author) / Loo, Yi Jia Valerie (Co-author) / Anderson, Karen (Thesis director) / Blattman, Joseph (Committee member) / Ferdosi, Shayesteh (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.
ContributorsO'Neill, Liam Martin (Author) / Sweazea, Karen (Thesis director) / Angadi, Siddhartha (Committee member) / Dickinson, Jared (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The main objective of this project is to create a hydrogel based material system to capture and release CCRF-CEM Leukemia cancer cells via chemo-mechanical modulation. This system is composed of an aptamer-functionalized hydrogel thin film at the bottom of a microfluidic channel, which changes its film thickness as the temperature of the fluid in the system changes. The functionalized hydrogel film has been created as the primary steps to creating the microfluidic device that could capture and release leukemia cells by turning the temperature of the fluid and length of exposure. Circulating tumor cells have recently become a highly studied area since they have become associated with the likelihood of patient survival. Further, circulating tumor cells can be used to determine changes in the genome of the cancer leading to targeted treatment. First, the aptamers were attached onto the hydrogel through an EDC/NHS reaction. The aptamers were verified to be attached onto the hydrogel through FTIR spectroscopy. The cell capture experiments were completed by exposing the hydrogel to a solution of leukemia cells for 10 minutes at room temperature. The cell release experiments were completed by exposing the hydrogel to a 40°C solution. Several capture and release experiments were completed to measure how many cells could be captured, how quickly, and how many cells captured were released. The aptamers were chemically attached to the hydrogel. 300 cells per square millimeter could be captured at a time in a 10 minute time period and released in a 5 minute period. Of the cells captured, 96% of them were alive once caught. 99% of cells caught were released once exposed to elevated temperature. The project opens the possibility to quickly and efficiently capture and release tumor cells using only changes in temperature. Further, most of the cells that were captured were alive and nearly all of those were released leading to high survival and capture efficiency.
ContributorsPaxton, Rebecca Joanne (Author) / Stephanopoulos, Nicholas (Thesis director) / He, Ximin (Committee member) / Gould, Ian (Committee member) / Materials Science and Engineering Program (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Prostate cancer is the second most common kind of cancer in men. Fortunately, it has a 99% survival rate. To achieve such a survival rate, a variety of aggressive therapies are used to treat prostate cancers that are caught early. Androgen deprivation therapy (ADT) is a therapy that is given in cycles to patients. This study attempted to analyze what factors in a group of 79 patients caused them to stick with or discontinue the treatment. This was done using naïve Bayes classification, a machine-learning algorithm. The usage of this algorithm identified high testosterone as an indicator of a patient persevering with the treatment, but failed to produce statistically significant high rates of prediction.
ContributorsMillea, Timothy Michael (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
As advanced as current cancer therapeutics are, there are still challenges that need to be addressed. One of them is the non-specific killing of normal cells in addition to cancerous cells. Ideal cancer therapeutics should be targeted specifically toward tumor cells. Due to the robust self-assembly and versatile addressability of DNA-nanostructures, a DNA tetrahedron nanostructure was explored as a drug carrier. The nanostructure can be decorated with various molecules to either increase immunogenicity, toxicity, or affinity to a specific cell type. The efficiency of the specific binding and internalization of the chosen molecules was measured via flow cytometry. Using a murine B cell lymphoma as the model system, several targeting molecules have been evaluated for their specific binding and induced internalization of DNA nanostructures, including an anti-Igκ antibody, an idiotype-binding peptide, and a g-quadruplex nucleolin specific aptamer. It was found that adding the anti-Igκ antibody appeared to provide increased binding and facilitated cellular internalization. Also, it was found that the presence of CpG appeared to aid in the binding of nanostructures decorated with other molecules, as compared to nanostructures without CpG. The g-quadruplex aptamer thought to specifically bind cancer cells that overexpress nucleolin was tested and found to have better binding to cells when linked to the nanostructure than when alone. The drug doxorubicin was used to load the DNA-nanostructure and attempt to inhibit cancer cell growth. The DNA-nanostructure has the benefit of being self-assembled and customizable, and it has been shown to bind to and internalize into a cancer cell line. The next steps are to test the toxicity of the nanostructure as well as its specificity for cancerous cells compared to noncancerous cells. Furthermore, once those tests are completed the structure’s drug delivery capacity will be tested in tumor bearing mice. The DNA-nanostructure exhibits potential as a cancer specific therapeutic.
ContributorsGomez, Amber Marie (Author) / Chang, Yung (Thesis director) / Anderson, Karen (Committee member) / Liu, Xiaowei (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12