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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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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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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
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
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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

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
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Description
Since the advent of DNA analysis, organizations such as the Innocence Project have been able to exonerate people who were wrongfully convicted of crimes, often due to erroneous forensic evidence analysis. In many cases, analytical techniques, such as fingerprint analysis, toolmark analysis, or hair comparisons have been cited as nearly

Since the advent of DNA analysis, organizations such as the Innocence Project have been able to exonerate people who were wrongfully convicted of crimes, often due to erroneous forensic evidence analysis. In many cases, analytical techniques, such as fingerprint analysis, toolmark analysis, or hair comparisons have been cited as nearly infallible sources of evidentiary fact. However, these methods rely on subjective interpretation by a forensic examiner and lack stringent, quantitative methods for ensuring reliability and accuracy. For most of these methods, the examiner is supplied only with the unknown sample from the crime scene, and a known sample from a suspect. This, combined with the influence of psychological factors such as confirmation bias, has resulted in the need for a reliable mechanism of ensuring the efficacy of a particular type of analysis as well as the objectivity, and competence of the analyst. One proposed method to resolve these issues is the use of a filler-control method, in which analysts are given an “evidence line-up” containing at least three samples: the unknown sample from the crime scene, a sample from the suspect, and at least one filler sample from an individual who is not involved in the investigation. This method provides a reliable method for estimating error rates for an analyst and can provide the analyst with direct feedback about their performance to accurately gauge their competence. This method also helps to prevent the introduction of confirmation bias, as the source of the samples is unknown to the analyst. The goal of the current research is to test the capacity of a filler-control method to lead to better confidence-calibration of examiners’ match judgements when compared to the conventional method. The hypothesis of this experiment is that participants using the filler control method will have improved performance and increased confidence calibration due to receiving feedback over the course of the trials when compared to participants using the traditional method.
ContributorsRocha, Bethany (Author) / Smalarz, Laura (Thesis director) / Kukucka, Jeff (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2022-05
DescriptionResearch has shown that adverse and traumatic events negatively affect a person's psychological outcome. However, research is lacking in the area examining at which life stage trauma is more harmful to experience. Additionally, the role of vulnerability and resilience factors may strengthen or ameliorate this relationship.
ContributorsColvin, Carah (Author) / Davis, Mary (Thesis director) / Lemery-Chalfant, Katheryn (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor)
Created2023-12