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- Creators: Barrett, The Honors College
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
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Description
Laboratory animals represent an invaluable, yet controversial, resource in the field of biomedical research. Animal research has been behind many influential discoveries in the field of emerging therapeutics. They provide the link between the theory of the lab bench and the functional application of medicine to influence human health. The use of animals in research is a consideration which must be heavily weighed, and the implementation must be carried out at a very high standard in order to retain research integrity and responsibility. We are in the process of conducting an experiment using laboratory mice to demonstrate cancer treatment using vaccinia (VACV) mutants as a possible oncolytic therapy for certain strains of melanoma. VACV is a double-stranded DNA poxvirus with a large and easily altered genome. This virus contains many genes dedicated to immune evasion, but has shown sensitivity to cell death by necroptosis in mouse studies (5). We have identified the absence of the kinase RIP3 which is vital in the necroptosis pathway as a potential target for oncolytic therapy using VACV mutants in specific strains of melanoma. Multiple groups of SCID Beige mice were inoculated with different melanoma cell lines and observed for tumor growth. Upon reaching 1 cm3 in volume, tumors were injected with either VACV- Δ83N, VACV- Δ54N, or PBS, and observed for regression. It was hypothesized that melanoma tumors that are RIP3-/- such as the MDA5 cell line will show regression, but melanoma tumors that are RIP3-positive and capable of necroptosis, such as the 2427 cell line, will resist viral replication and continue to proliferate. Our results so far tentatively support this hypothesis, but the data collection is ongoing. Strict and specific protocols with regard to the ethical and responsible use of mice have been implemented and upheld throughout the experiment. Animals are closely monitored, and if their quality of life becomes too poor to justify their continued use in the experiment, they are humanely euthanized, even at the expense of valuable data. The importance of commitment to a high ethical standard is pervasive throughout our work. Animals represent an invaluable contribution to research, and it is important to maintain high standards and transparency with regard to their use. Education and engagement in critical discussions about the use and care of animals in the laboratory contribute to the overall merit and legitimacy of biomedical research in the public and professional eye as a whole, and give legitimacy to the continued use of animals as models to advance science and health.
ContributorsBergamaschi, Julia (Author) / Kibler, Karen (Thesis director) / Jacobs, Bertram (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Bats (order Chiroptera) are the longest lived mammals for their size, with particularly extreme longevity evolving in the family Vespertilionidae, or vesper bats. Because of this, researchers have proposed using bats to study ageing and cancer suppression. Here, we study gene duplications across mammalian genomes and show that, similar to previous findings in elephants, bats have experienced duplications of the tumor suppressor gene TP53, including five genomic copies in the genome of the little brown bat (Myotis lucifugus) and two copies in Brandt's bat (Myotis brandtii). These species can live 37 and 41 years, respectively, despite having an adult body mass of only ~7 grams. We use evolutionary genetics and next generation sequencing approaches to show that positive selection has acted on the TP53 locus across bats, and two recently duplicated TP53 gene copies in the little brown bat are both highly conserved and expressed, suggesting they are functional. We also report an extraordinary genomic copy number expansion of the tumor suppressor gene FBXO31 in the common ancestor of vesper bats which accelerated in the Myotis lineage, leading to 34\u201457 copies and the expression of 20 functional FBXO31 homologs in Brandt's bat. As FBXO31 directs the degradation of MDM2, which is a negative regulator of TP53, we suggest that increased expression of both FBXO31 and TP53 may be related to an enhanced DNA-damage response to genotoxic stress brought on by long lifespans and rapid metabolic rates in bats.
ContributorsSchneider-Utaka, Aika Kunigunda (Author) / Maley, Carlo (Thesis director) / Wilson Sayres, Melissa (Committee member) / Tollis, Marc (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Cancer is the second leading cause of death in the United States. Cancer is a serious, complex disease which causes cells to grow uncontrollably, causing millions of deaths per year [1]. Cancer is usually caused by a combination of environmental variables and biological pathways. The pathways have a very robust structure normally, but are altered because of cancer, resulting in a loss of connectivity between pathways. In order detect these pathways, a PageRank-based method called Pathways of Topological Rank Analysis (PoTRA) was created, which measures the relative rankings of the genes in each pathway. Applying this algorithm will allow us to figure out what pathways differed significantly in areas with cancer and areas without cancer. This would allow scientists to focus on specific pathways in order to learn more about the cancer and find more effective ways to treat it. So far, analysis using PoTRA has been successfully conducted on hepatocellular carcinoma (HCC) and its subtypes, resulting in all significant pathways found being cancer-associated. Now, using the TCGA data stored in Google Cloud's BigQuery, we created a pipeline to apply PoTRA to other cancer data sets and see how well it cross-applies to other cancers. The results show that even though some modification may need to be made to adapt to other datasets, many significant pathways were found for both HCC and breast cancer.
ContributorsMahesh, Sunny Nishant (Author) / Valentin, Dinu (Thesis director) / Liu, Li (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Nutritional support offered before and during chemotherapy treatment is proven to improve the outcomes of treatment (Bernhardson, 2016). This project seeks to examine current forms of nutritional support offered to patients, as well as the models of care and support teams in cancer treatment centers. The basis for this project incorporated personal experiences at M.D. Anderson Cancer Center in Gilbert, Arizona as well as research into the work of clinical oncology dietitians. An intense interest in food videos and blogs also informed this project, and was incorporated in the hope of providing chemotherapy patients a platform to discover recipes specific to their unique situation. The combination of this research was utilized to create several videos which demonstrated specific recipes beneficial for patients as well as creating a platform for this particular population. While nutritional support can take multiple forms, the focus of nutritional support surrounds symptom management. The common side effects of chemotherapy such as nausea, mucositis (mouth sores), and extreme weight loss were taken into account. Recipes were formulated to directly address these conditions and each recipe was broken down into the benefits of both macronutrients and micronutrients. In addition to formulating specific recipes and videos, barriers to proper nutritional support were examined and explained. These barriers include understaffing of clinical dietitians at cancer treatment centers, a patient's lack of transportation to and from treatments, as well as an overwhelming viewpoint that nutritional support is only required for extreme cases of malnutrition. Combatting these barriers and offering more forms of nutritional support will help to increase a patient's positive response to treatment, manage their symptoms, and improve their overall quality of life.
ContributorsMonteilh, Christina Eleanor (Author) / Levinson, Simin (Thesis director) / Martinelli, Sarah (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Chemotherapy refers to the use of chemical agents to inhibit or stop the growth of rapidly dividing cancer cells. There are many side effects of systemic chemotherapy, which are caused because the drug not only kills cancer cells but healthy cells as well (American Cancer Society, 2017). Common side effects include fatigue, hair loss, bruising/ bleeding, infection, anemia, nausea and vomiting, appetite changes, constipation, diarrhea, oral sores, nerve and muscle pain, dry skin and color change, kidney dysfunction, weight loss, cognitive difficulties, mood changes, sexual dysfunction, and fertility problems (American Cancer Society, 2017). Research shows that complementary and alternative medicine (CAM) may help relieve some of the side effects of chemotherapy. Examples of CAM include herbal medicine, dietary supplements, acupuncture, yoga, Tai Chi, massage, electromagnetic therapy, meditation, biofeedback, music, dance, and guided imagery (Johns Hopkins Medicine, 2017). The aim of this creative project was to design a third-party website to provide information to patients undergoing chemotherapy and their family members regarding the use of CAM for the treatment of chemotherapy-induced side effects. Rationale for this project stemmed from a preliminary research step. We analyzed and coded for presence or absence of CAM-specific information on the websites of 20 National Cancer Institute-designated comprehensive cancer centers across the United States. Fifty percent of websites were double-coded. Inter-rater reliabilities (kappa values) for coding of the presence or absence of specific CAM therapies ranged from 0.38 for acupuncture to 1.00 for exercise and yoga, expressive arts, and herbs (mean kappa = 0.75). Fourteen of the 20 websites mentioned meditation or mindfulness; 13 mentioned nutrition; 12 mentioned acupuncture; 11 mentioned exercise or yoga; 11 mentioned massage; 8 mentioned expressive arts; and 3 mentioned herbs. Frequencies for presence of either a description of the specific CAM therapy or an explanation of how the therapy works were lower. We then conducted a literature review using PUBMED to find peer-reviewed research on the efficacy of the previously described seven CAM therapies. The literature search focused on systematic reviews and meta-analyses published within the past 10 years. Based on the literature obtained, we created summaries of the scientific evidence for each CAM therapy. This information is now provided on our third-party website in tabular form with summative statements. The website describes in lay language: chemotherapy, chemotherapy side effects, CAM, seven specific CAM therapies, and evidence for the efficacy or lack thereof of each. Per the American Nurses Association (2015), it is our responsibility to advocate for our patients through education and holistic treatment. The role of the nurse is to educate the patient about treatment options; however, it is not within the nurse's scope of practice to prescribe a treatment. As such, this website should not be viewed as a prescription for CAM therapies, but instead as a user-friendly and easily accessible resource for informed decision-making regarding the adjunctive use of CAM therapies.
ContributorsNichols, Abrianna (Co-author) / Varosky, Maxwell (Co-author) / Langer, Shelby (Thesis director) / Morris, Brenda (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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