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- All Subjects: Bexarotene
- All Subjects: Vitamin B12
- Creators: Hackney Price, Jennifer
- Creators: Moore, Marianne
- Resource Type: Text
- 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 (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
Vitamin supplements have beneficial and adverse effects depending on the dosage given and the age and sex of the recipient. Vitamin supplements have been extremely profitable in the health industry, but there is limited scientific data supporting vitamin supplement benefits. Many studies over the last decade have shown that vitamin supplements provide few health benefits and can lead to adverse effects, such as abnormal bone growth, birth defects, or an increased risk of cancer. Some researchers state that people with a specific vitamin deficiency should take vitamin supplements because the supplement can alleviate this deficiency. Many healthy people take vitamin supplements to prevent disease or have better health, but some researchers argue this is a misconception. Most health organizations indicate that consuming vitamins should be through diet, not supplements. The value of dietary supplements, most of which are consumed in developed countries, has been a controversial topic, because the beneficial effects of taking vitamin supplements is hotly contested. Many experts in the field of nutritional physiology suggest that Americans adequately receive enough vitamins in their diet and do not need to take vitamin supplements. Researchers at John Hopkins announced that the United States should stop spending money on vitamin supplements. Their research has found no benefits to taking vitamin supplements, because most people in industrialized areas are well-nourished. In this study, I have gathered that vitamin supplements are not beneficial when one has a sufficiently nutrient-rich diet; whereas, one who has a vitamin deficient diet can benefit from taking vitamin supplements. Furthermore, I have gathered that people older than 65-years-old should take vitamin B12 because vitamin B12 levels decrease with age. There is not enough evidence to prove or disprove that vitamin supplements are generally beneficial. In fact, I gathered that vitamin supplements may even be harmful. I propose that further studies should be conducted to discover the truth about the possible benefits of vitamin supplementation for healthy individuals and among people with different health conditions, activity levels, and nutrient requirements.
ContributorsMcDowell, Alexandra Catherine Jo (Author) / Moore, Marianne (Thesis director) / Huffman, Holly (Committee member) / College of Integrative Sciences and Arts (Contributor) / Department of Management and Entrepreneurship (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Vitamin D3 (cholecalciferol) is an essential micronutrient that plays a key role in developmental growth and lifespan in mammals. However, few studies have shown how vitamin D3 plays its vital functions in arthropods. Here, we examined the effects of full (13.3 IU/mL) and half dose (6.65 IU/mL) vitamin D3 on the growth and lifespan of Drosophila melanogaster. Vitamin B12 is another micronutrient that shows decreases absorption in elderly patients and might be linked to symptoms associated with aging rather than lifespan, but again, the effects of vitamin B12 supplementation in arthropods is poorly characterized. Results showed that both full and half doses of vitamin D3 and B12 do not significantly alter the timing of pupariation or adult eclosion. Similarly, the mortality rate of adult D. melanogaster exposed to vitamin B12 or higher doses of vitamin D3 was not significantly decreased or increased. However, a low dose of vitamin D3 did significantly lower the mortality rate of D. melanogaster. The genetic composition of Drosophila for vitamin B12 and D metabolism showed similarities in humans. However, there are no biological evidences if these genes are functional thus, this may explain the results of this study.
ContributorsRebonza, Edzel May Suico (Author) / Hackney Price, Jennifer (Thesis director) / Jurutka, Peter (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05