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- All Subjects: Bexarotene
- Creators: School of Mathematical and Natural Sciences
- Creators: Marshall, Pamela
- Resource Type: Text
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
The effects that forensic-themed programs such as CSI: Crime Scene Investigation has on the public's understanding and expectations of the criminal justice system has been a main focus of study in recent years. This phenomenon was coined by the media and termed the "CSI Effect." This study aimed to research the correlations between age, gender, and program-watching habits on potential juries' evidence expectations in court. To do so, 70 people were surveyed and asked a series of demographic questions, as well as questions about how often they watch forensic-themed shows and their experience with the criminal justice system. They were given a mock crime scene scenario and asked about their scientific and non-scientific evidence expectations in this particular case. The most notable results showed that a longer exposure time to forensic-themed programs correlated to high evidence expectations. However, how often viewers watch forensic-themed programs did not seem to affect their evidence expectations. It was concluded that the higher evidence expectations by modern jurors may be due to a combination of the "CSI Effect" and the newly hypothesized "Tech Effect," instead of just being the consequence of the watching too much forensic-themed television.
ContributorsJones, Kristin Taylor (Author) / Kobojek, Kimberly (Thesis director) / Lafond, Sue (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2014-05
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
It is no surprise that crime has become an interest to people both nationally and globally. It is impossible to turn on a TV without hearing cable news talking about a bank robbery or a murder, or a political hearing of some sort. Crime TV shows are incredibly common—there are whole channels dedicated to just crime, and many prime-time TV shows deal with some form of crime, most often the law enforcement teams that interact with it. Movies and books about crime are also incredibly common—most movie theaters have at least one horror movie or psychological thriller on show at a given time, and books stores and libraries have entire sections about true crime and mysteries.
Crime has become an inescapable part of being a consumer and viewer in today’s society. The interest in crime, however, could not have just been created by the media or a few specific parties and gained the amount of attention that is has today. Crime has been of interest since ancient times, seen immortalized in art and literature with famous events like the death of Socrates and the assassination of Julius Caesar. However, only more modern advances in media and the growth in consumerism could have led to interest and commodification of crime as we see it today. Landmark cases like Ted Bundy and O.J. Simpson have contributed to the growth of the media landscape, but because of the cyclical nature of the news and consumer cycle, these cases would not differ much in the way that they would be covered today, even with the new methods of disseminating information that we have today, such as social media and news websites that are accessible by everyone. Crime as entertainment has been a product not just of the media and popular culture but also from American consumers who continue to give media and pop culture producers a consumer who wishes to view their content and to continue to further the interest in crime. Media and popular culture are not the only people to blame for the popularization of crime as a product; people in the United States, and globally, are just as much responsible for the creation of crime as entertainment.
Crime has become an inescapable part of being a consumer and viewer in today’s society. The interest in crime, however, could not have just been created by the media or a few specific parties and gained the amount of attention that is has today. Crime has been of interest since ancient times, seen immortalized in art and literature with famous events like the death of Socrates and the assassination of Julius Caesar. However, only more modern advances in media and the growth in consumerism could have led to interest and commodification of crime as we see it today. Landmark cases like Ted Bundy and O.J. Simpson have contributed to the growth of the media landscape, but because of the cyclical nature of the news and consumer cycle, these cases would not differ much in the way that they would be covered today, even with the new methods of disseminating information that we have today, such as social media and news websites that are accessible by everyone. Crime as entertainment has been a product not just of the media and popular culture but also from American consumers who continue to give media and pop culture producers a consumer who wishes to view their content and to continue to further the interest in crime. Media and popular culture are not the only people to blame for the popularization of crime as a product; people in the United States, and globally, are just as much responsible for the creation of crime as entertainment.
ContributorsCooke, Emilie (Author) / Kobojek, Kimberly (Thesis director) / Gordon, Karen (Committee member) / School of Criminology and Criminal Justice (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05