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- Creators: School of Social and Behavioral Sciences
- Status: Published
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 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
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 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
Description
Bexarotene (Bex) is a FDA-approved drug used to treat cutaneous T-cell lymphoma (CTCL). It binds with high affinity to the retinoid-X-receptor (RXR), a nuclear receptor implicated in numerous biological pathways. Bex may have the potential to attenuate estrogenic activity by acting as an estrogen receptor alpha (ERα) signaling antagonist, and can therefore be used to treat ERα-positive cancers, such as breast cancer. Using dual luciferase reporter assays, real-time qRT-PCR, and metabolic proliferation assays, the anti-estrogenic properties of Bex were ascertained. However, since Bex produces numerous contraindications, select novel RXR drug analogs were also evaluated. Results revealed that, in luciferase assays, Bex could significantly (P < 0.01) inhibit the transcriptional activity of ERα, so much so that it rivaled ER pan-antagonist ZK164015 in potency. Bex was also able to suppress the proliferation of two breast cancer cell models, MCF-7 and T-47D, and downregulate the expression of an estrogen receptor target gene (A-myb), which is responsible for cell proliferation. In addition, novel analogs A30, A33, A35, and A38 were evaluated as being more potent at inhibiting ERE-mediated transcription than Bex at lower concentrations. Analogs A34 and A35 were able to suppress MCF-7 cell proliferation to a degree comparable to that of Bex. Inhibition of T-47D cell proliferation, by contrast, was best achieved by analogs A34 and A36. For those with ERα – positive breast cancer who are refractory to current chemotherapeutics used to treat breast cancer, Bex and its analogs may prove to be useful alternative options.
ContributorsBains, Supreet (Author) / Jurutka, Peter (Thesis director) / Hackney Price, Jennifer (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The goal of this thesis was to create a resource addressing non-course-specific (NCS) student needs that College of Integrative Sciences and Arts (CISA) faculty can provide to their students when appropriate. Students attend faculty office hours for a variety of reasons, and not all are academic in nature. Data was collected in order to determine which resources were lacking in addressing these needs. Student need was identified through a 13-item survey regarding faculty perception of NCS student needs, including the primary reason for office hour visitation and the primary sources of stress, academic advising, and time management complaints from their students. Additionally, feedback was collected regarding faculty perception of available resources and likelihood of utilizing a new resource. Throughout the Downtown, Tempe, and Polytechnic campuses, 24 faculty responded. It was found that work stress, familial stress, academic advising requests, and students comments of being overwhelmed were the primary NCS student needs as perceived by faculty. Additionally, the majority of faculty reported not feeling fully equipped to address these needs. This information was used to create a resource compiling a list of University and off-campus tools that students can access to address these needs. The resource combined data from faculty and from the literature to address general and specific issues of stress, academic advising, feeling ‘off,’ and recovery and was created a double-sided handout to be used electronically or for print. It is currently available for faculty use. With further research, this resource could be expanded or refined to address the needs of a larger population of students in different colleges or on different campuses. Eventually, this could be used as a University-wide tool.
ContributorsMcAnally, Kaylyn Marie (Author) / Chisum, Jack (Thesis director) / Lisenbee, Cayle (Committee member) / School of Social and Behavioral Sciences (Contributor) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This research explores how to best communicate positive body images to women. This project was intended to improve a blog I created my freshmen year in college called You're Not A Potato where I used original illustrations to tell a narrative about body image issues. The thesis begins with an historical overview of body image issues and finds that women have been dealing with high levels of body dissatisfaction since the Victorian era. The thesis then recaps the role of traditional media as well as contemporary social media and the role they play in imposing rigid beauty ideals on women's bodies. After an analysis of social media culture, it becomes evident women still communicate about their bodies in a negative manner, not only towards themselves, but towards others. To address this issue, I define the Body Positive movement and explore how public figures are using social media to implement Body Positivity. To conclude this project, I utilize my new-found knowledge in body positive communication by impacting my university campus community. I started a "You're Not a Potato" Campaign for Body Pride week with the help of the ASU Wellness Team and designed and facilitated several engaging programs that reflected the values of the Body Positive movement to our students. Through this research, I discovered how our appearance-based culture has stolen self-confidence from young women today, but by the end of this project, I explain how we can attempt to rebuild our culture by effectively communicating self-love and body acceptance in our online and physical communities.
ContributorsMouton, Brianna Anais (Author) / Gruber, Diane (Thesis director) / Taylor, Jameien (Committee member) / Manninen, Bertha (Committee member) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Numerous studies have established that during the transition to parenthood couples experience changes within their relationship as well as in their overall mental health. The present study examines these changes specifically through conflict interactions. The author proposes the more conflict that occurs within a relationship, the lower each individual's self-esteem; the lowered self-esteem then leads to signs of depression. The present study's analysis consisted of two primary aims: 1) examine the association between romantic relationship conflict and mental health by using a proposed mediational pathway, in which self-esteem explains the connection, and 2) explore gender differences. The study aims were examined using secondary data analyses of Dr. Kristin Mickelson's study on couples transitioning to parenthood (Baby TIME Study). Results varied by conflict type as well as gender. When conflict was measured by perceived negative spousal interactions, results showed that the proposed mediational pathway was significant for men, but not for women. When conflict was measured by frequency of spousal arguments, results showed that the proposed mediational pathway was significant for women, but not for men. Furthermore, the results from this analysis indicate that during the transition to parenthood, men and women are affected by conflict differently in regards to their self-esteem and further their reported levels of depression.
ContributorsHoyt, Alyssa Aileen (Author) / Mickelson, Kristin (Thesis director) / Hall, Deborah (Committee member) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Trauma is increasingly experienced by people in transit as border militarization increases migrants’ exposure to violence and forces them into more precarious situations. For queer migrants, this includes situations where they are more likely to experience persecution and sexual violence. This paper explores the availability of care for queer undocumented migrants in the United States after surviving a precarious and potentially deadly journey from their country of origin to the US, as well as forms of alternative care developed by the undocuqueer community. In particular, it focuses on access to care for LGBT migrants, who face stigmatization on multiple levels and as a result are more likely than their straight counterparts to experience extreme mental health consequences pre-, in-, and post-transit. Faced with a number of obstacles that prevent them from receiving appropriate mental health care, the undocuqueer community utilizes various strategies to ensure that the health and needs of the community are supported. I argue that in spite of facing traumatic experiences and being unable to fully access healthcare to alleviate these problems in the US, LGBT migrants demonstrate extreme resilience and resist the mechanisms that otherwise threaten their mental well-being.
ContributorsCordwell, Cailan Rose (Author) / Wheatley, Abby C. (Thesis director) / Ward, Mako Fitts (Committee member) / School of Human Evolution & Social Change (Contributor) / Department of Psychology (Contributor) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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 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
Description
Bexarotene is a Food and Drug administration (FDA)-approved therapeutic used in the treatment of cutaneous T-cell lymphoma (CTCL). However, bexarotene therapy causes significant side effects like hyperlipidemia and hypothyroidism due to crossover activity with retinoic acid receptor (RAR), thyroid hormone receptor (TR), and liver X receptor (LXR) signaling, respectively. More recently bexarotene has shown promise to reverse neurodegeneration, improve cognition and decrease levels of amyloid- β in transgenic mice expressing familial Alzheimer’s disease (AD) mutations. Bexarotene is a high affinity ligand for the retinoid X receptor (RXR) that heterodimerizes with the liver- X- receptors (LXR) and with peroxisome proliferator-activated receptor-gamma (PPARϒ) to control cholesterol efflux, inflammation, and transcriptionally upregulates the production of apolipoprotein (ApoE) in the brain. Enhanced ApoE expression may promote clearance of soluble Aβ peptides from the brain and reduce Aβ plaques, thus resolving both amyloid pathology and cognitive deficits. The present study assessed the potential of bexarotene and a group of 62 novel rexinoids to bind and activate RXR using a series of biological assays and screening methods, including: 1) a mammalian two-hybrid system (M2H) and an 2) Retinoid X Receptor response element (RXRE)-mediated reporter assays in cultured human cells. Moreover, Liver X Receptor response element (LXRE)-mediated luciferase assays were performed to analyze the ability of the novel analogs to activate LXRE - directed transcription, and to induce ApoE messenger ribonucleic acid (mRNA) in U87 glial cells. Furthermore, the most potent analogs were analyzed via quantitative polymerase chain reaction (qPCR) to determine efficacy in modulating expression of two critical tumor suppressor genes, activating transcription factor 3 (ATF3) and early growth response 3 (EGR3). Results from these multiple assays indicate that the panel of RXR ligands contains compounds with a range of activities, with some analogs capable of binding to RXR with higher affinity than others, and in some cases upregulating ApoE expression to a greater extent than bexarotene. The data suggests that minor modifications to the bexarotene core chemical structure may yield novel analogs possessing an equal or greater capacity to activate RXR and may be useful as therapeutic agents against CTCL and Alzheimer’s disease.
ContributorsReshi, Sabeeha Mushtaq (Author) / Jurutka, Peter (Thesis advisor) / Wagner, Carl (Committee member) / Marshall, Pamela (Committee member) / Arizona State University (Publisher)
Created2023
Description
The portrayal of those with mental health disorders in film and television, particularly those with disorders that label them as psychopaths, have often been overlooked. It is all too common for mental health disorders to be romanticized, dramatized, or simply depicted incorrectly. The historical fiction films Extremely Wicked, Shockingly Evil and Vile and My Friend Dahmer depict serial killers Ted Bundy and Jeffrey Dahmer respectively, and while depict historical events to a degree of accuracy, still take creative liberties. The proper definition of psychopathy must be analyzed more and the reason why films about psychopaths are popular with audiences must be as well.
ContributorsCompanik, Noah (Author) / Arce, Alma (Thesis director) / Gruber, Diane (Committee member) / Barrett, The Honors College (Contributor) / School of Criminology and Criminal Justice (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2022-05