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Characterization of Second and Third Generation, Novel RXR Selction Agonists for the Treatment of Cutaneous T-Cell Lymphoma

Description
Bexarotene is a commercially produced drug commonly known as Targetin presecribed to treat cutaneous T-cell lymphoma (CTCL). Bex mimics the actions of natural 9-cis retinoic acid in the body, which are derived from Vitamin A in the diet and boost the immune system. Bex has been shown to be effective…

Bexarotene is a commercially produced drug commonly known as Targetin presecribed to treat cutaneous T-cell lymphoma (CTCL). Bex mimics the actions of natural 9-cis retinoic acid in the body, which are derived from Vitamin A in the diet and boost the immune system. Bex has been shown to be effective in the treatment of multiple types of cancer, including lung cancer. However, the disadvantages of using Bex include increased instances of hypothyroidism and excessive concentrations of blood triglycerides. If an analog of Bex can be developed which retains high affinity RXR binding similar to the 9-cis retinoic acid while exhibiting less interference for heterodimerization pathways, it would be of great clinical significance in improving the quality of life for patients with CTCL. This thesis will detail the biological profiling of additional novel (Generation Two) analogs, which are currently in submission for publication, as well as that of Generation Three analogs. The results from these studies reveal that specific alterations in the core structure of the Bex "parent" compound structure can have dramatic effects in modifying the biological activity of RXR agonists.
ContributorsYang, Joanna (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Hibler, Elizabeth (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
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Analysis of Retinoid X Receptor (RXR) Homodimerization Driven by RXR Ligands Using Yeast Two-Hybrid

Description
Bexarotene (Targretin®) is an FDA approved drug used to treat cutaneous T-cell lymphoma (CTCL), as well as off-label treatments for various cancers and neurodegenerative diseases. Previous research has indicated that bexarotene has a specific affinity for retinoid X receptors (RXR), which allows bexarotene to act as a ligand-activated-transcription factor…

Bexarotene (Targretin®) is an FDA approved drug used to treat cutaneous T-cell lymphoma (CTCL), as well as off-label treatments for various cancers and neurodegenerative diseases. Previous research has indicated that bexarotene has a specific affinity for retinoid X receptors (RXR), which allows bexarotene to act as a ligand-activated-transcription factor and in return control cell differentiation and proliferation. Bexarotene targets RXR homodimerization to drive transcription of tumor suppressing genes; however, adverse reactions occur simultaneously when bound to other nuclear receptors. In this study, we used novel bexarotene analogs throughout 5 iterations synthesized in the laboratory of Dr. Wagner to test for their potency and ability to bind RXR. The aim of our study is to quantitatively measure RXR homodimerization driven by bexarotene analogs using a yeast two-hybrid system. Our results suggests there to be several compounds with higher protein activity than bexarotene, particularly in generations 3.0 and 5.0. This higher affinity for RXR homodimers may help scientists identify a compound that will minimize adverse effects and toxicity of bexarotene and serve as a better cancer treatment alternative.
ContributorsSeto, David Hua (Author) / Marshall, Pamela (Thesis director) / Wagner, Carl (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2015-05
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Latina Women in STEM: How Race and Class Shape the Experiences of Undergraduate Women in STEM Majors at Arizona State University

Description
Women and people of color are some of the most underrepresented groups in the STEM field (science, technology, engineering, and mathematics). The purpose of this study was to uncover the barriers that undergraduate Hispanic women, as well as other women of color, face while pursuing an education in a STEM-related…

Women and people of color are some of the most underrepresented groups in the STEM field (science, technology, engineering, and mathematics). The purpose of this study was to uncover the barriers that undergraduate Hispanic women, as well as other women of color, face while pursuing an education in a STEM-related major at Arizona State University (ASU). In-depth interviews were conducted with 13 adult participants to dig deeper into the experiences of each woman and analyze how race and class overlap in each of the women's experiences. The concept of intersectionality was used to highlight various barriers such as perceptions of working versus middle-class students, the experience of being a first-generation college student, diversity campus-wide and in the classroom, effects of stereotyping, and impacts of mentorships. All women, no matter their gender, race, or socioeconomic status, faced struggles with stereotyping, marginalization, and isolation. Women in STEM majors at ASU performed better when provided with positive mentorships and grew aspirations to become a professional in the STEM field when encouraged and guided by someone who helped them build their scientific identities. Working-class women suffered from severe stress related to finances, family support, employment, and stereotyping. Reforming the culture of STEM fields in higher education will allow women to achieve success, further build their scientific identities, and increase the rate of women graduating with STEM degrees.
ContributorsValdivia, Lilianna Alina (Author) / Kim, Linda (Thesis director) / Camacho, Erika (Committee member) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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A Correlational Study of the Relationship between Stress, Empathy, and Emotion Regulation in Young Adults

Description
Stress, empathy, and emotion regulation are factors that can greatly shape an individual's behavior, thoughts, and physiology. The degree to which an individual experiences stress, demonstrates empathy, or is able to regulate emotions can influence his or her ability to establish strong social bonds. The current study investigated the relationships…

Stress, empathy, and emotion regulation are factors that can greatly shape an individual's behavior, thoughts, and physiology. The degree to which an individual experiences stress, demonstrates empathy, or is able to regulate emotions can influence his or her ability to establish strong social bonds. The current study investigated the relationships among stress, empathy, and emotion regulation and considered gender differences in these relationships. I hypothesized that higher levels of current stress would be associated with lower levels of empathy and greater difficulties with emotion regulation, and that empathy and emotion regulation would be positively related. Supporting these hypotheses, the following relationships were found: (a) negative correlation between stress and empathy, (b) positive correlation between stress and emotion regulation difficulties, and (c) negative correlation between empathy and emotion regulation difficulties. Results also revealed that greater perceived stress was associated with less empathy in women, but it was unrelated to empathy in men. On the other hand, stress was associated with greater emotion regulation difficulties in both men and women, indicating that either gender may experience a greater disturbance in their emotional response within a social situation when under the influence of stress. Empathy and emotion regulation are positively correlated in both genders, which might suggest that high emotion regulation may allow for appropriate empathy responses within a given social context.
ContributorsHanna, Rand Maria (Author) / Roberts, Nicole (Thesis director) / Burleson, Mary (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2016-12
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The Effects of Acoustic Stress on the Behavior of Drosophila melanogaster

Description

Veterans are approximately 30% more likely than non-veterans to suffer from severe hearing impairment. Tinnitus, or ringing in the ears, which is increasingly common among military service men and women, has been linked to significant cognitive and psychological impairment and can be worsened by the same sounds that trigger post-traumatic…

Veterans are approximately 30% more likely than non-veterans to suffer from severe hearing impairment. Tinnitus, or ringing in the ears, which is increasingly common among military service men and women, has been linked to significant cognitive and psychological impairment and can be worsened by the same sounds that trigger post-traumatic stress disorder (PTSD). In fact, tinnitus and PTSD often present as comorbidities, and recent studies suggest these two disorders may share a common neurological pathway. Additional studies are required to better understand the connection between hearing loss and impaired cognitive function such as that observed in with PTSD. Here, we use the fruit fly, Drosophila melanogaster, to explore the relationship between hearing loss and cognitive function. Negative geotaxis climbing assays and courtship behavior analysis were used to examine neurobehavioral changes induced by prolonged, intense auditory stimulation. Preliminary results suggest that exposure to loud noise for an extended period of time significantly affected Drosophila behavior, with males being more sensitive than females. Based on our results, there appears to be a potential connection between noise exposure and behavior, further suggesting that Drosophila could be an effective model to study the link between hearing loss and PTSD.
ContributorsMichael, Allison Faye (Author) / Hackney-Price, Jennifer (Thesis director) / Sellner, Erin (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05

Evaluation of Novel Therapeutics for Cancer and Alzheimer's Disease

Description

The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application…

The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application of novel analogs of Bexarotene (RXR agonist), MeTC7 (a new potent VDR antagonist), and vitamin D as possible therapeutics for cancer and Alzheimer’s disease.
ContributorsHong, Jennifer (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Marshall, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-05