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Undergraduate Honors Theses

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Articles 1 - 15 of 15

Full-Text Articles in Cancer Biology

Frost450, A Novel Microtubule Targeting Agent: Resistance And Cross-Resistance In An Ovarian Cancer Cell Line, Jonathan Chancellor Fox Dec 2018

Frost450, A Novel Microtubule Targeting Agent: Resistance And Cross-Resistance In An Ovarian Cancer Cell Line, Jonathan Chancellor Fox

Undergraduate Honors Theses

Drug resistance remains problematic for chemotherapy treatments. As primary treatment strategies tend to lose potency against cancer, there is a need for treatment options that overcome drug resistance mechanisms. FROST450, a novel microtubule destabilizing agent, has proven anticancer effects that overcome taxane and multidrug resistance. However, to better understand the clinical potential of FROST450, in this study we examine the mechanisms and implications of acquired FROST450 resistance in an A2780 ovarian cancer cell line. Results indicate FROST450 resistance is associated with increased mitochondrial respiration and with changes in gene sequence or expression level of proteins associated with microtubules, and that ...


Alk-Eml4-Positive Cancers And Combination Therapy: Probing The Apoptotic Threshold, Teagan Glass Jan 2018

Alk-Eml4-Positive Cancers And Combination Therapy: Probing The Apoptotic Threshold, Teagan Glass

Undergraduate Honors Theses

Of all diseases currently being researched, lung cancer is one of the most pressing due to its worldwide prevalence and high incidence of fatality. More specifically, non-small cell lung cancers (NSCLC) harboring ALK-EML4 gene fusion mutations are of particular interest to researchers due to their widely documented capability of becoming resistant to specialized treatment, such as kinase inhibition. This project was initiated with the aim of using in vitro combination drug treatment to more efficaciously inhibit the growth and survival of H3122 cells, an ALK-EML4-positive NSCLC cell line. In this study, H3122 cells were subjected to combined ALK and histone ...


Receptor Gone Rogue: Investigating Localization Of A Cancerous Thyroid Hormone Receptor, Michelle Barbeau May 2017

Receptor Gone Rogue: Investigating Localization Of A Cancerous Thyroid Hormone Receptor, Michelle Barbeau

Undergraduate Honors Theses

Thyroid hormone receptors play a crucial role in regulating differentiation, growth and development in response to thyroid hormone, and mutations in these receptors can have severe medical consequences ranging from endocrine dysfunction to cancer. Tumors of patients with hepatocellular carcinoma (HCC) display a high incidence of mutant thyroid hormone receptors (TRs), and one such mutant is TRα1 (K74E, A264V). The binding partners and gene targets of this mutant have been characterized, but the role of intracellular localization in the pathogenesis of TRα1 (K74E, A264V) has not yet been determined. Here, it was observed that the mutant receptor has a tendency ...


The Association Of Dcc Mrna Alternative Splicing With Colorectal Cancer, Natalie Graham Jan 2017

The Association Of Dcc Mrna Alternative Splicing With Colorectal Cancer, Natalie Graham

Undergraduate Honors Theses

In as many as 70% of colorectal cancer cell (CRC) lines, there is a deletion of a chromosomal region, 18q21, which contains the Deleted in Colorectal Carcinoma (DCC) gene (Mehlen & Fearon, 2004). In adult cells, this single transmembrane receptor plays a role in both cell proliferation and cell death, thereby making it a promising candidate gene for the pathogenesis of colorectal cancer. It has been observed that alternative splicing of the DCC can affect its activity and that alternative splicing of DCC can be disrupted in cancer (Leggere et al., 2016; Reale et al., 1994). In this experiment, we sought to determine the association of alternative splicing of the DCC with colorectal cancer in cells without the deletion of the 18q21 region. By extracting RNA from 35 CRC cell lines and performing RT-PCR, we observed levels of the two DCC isoforms compared to normal adult colon cells. In this way, we determined that 29 of 35 CRC cell lines had altered ...


Homothorax Is A Modifier Of Radiation Sensitivity In Drosophila Melanogaster Bantam Mutants, Geoffrey Meyerhof Jan 2017

Homothorax Is A Modifier Of Radiation Sensitivity In Drosophila Melanogaster Bantam Mutants, Geoffrey Meyerhof

Undergraduate Honors Theses

Radiation resistance in human cancers represents a massive impediment for successful tumor treatment. The fruit fly Drosophila melanogaster is an excellent model for human radiation resistance because of its largely conserved apoptotic pathways and malleable genome. This thesis investigates the genetic regulatory mechanisms for bantam (ban), an anti-apoptotic microRNA. To first identify genes that interact with ban, a forward genetic screen was conducted. This screen looked for genes that yielded radiation dependent pupal lethality in a ban deficient background. From this screen the transcription factor, homothorax, was identified as displaying radiation dependent synthetic lethality with ban. To investigate the mechanism ...


Characterization Of Tumor Protein P63 Regulated 1-Like Function In Xenopus Laevis, Julia Mo Jan 2017

Characterization Of Tumor Protein P63 Regulated 1-Like Function In Xenopus Laevis, Julia Mo

Undergraduate Honors Theses

Of the approximately 20,000 genes in the human genome, about 6,000 have unknown or poorly characterized function. Tumor protein p63 regulated 1-like (TPRG1l) is one of those genes with no functional data. TPRG1L is expressed during embryonic development and adulthood with strongest expression in the brain. It is implicated in carcinogenesis because its gene expression is activated by tumor regulators p63/73. To elucidate TPRG1L function during embryogenesis, CRISPR-Cas9 genome editing system was utilized to induce Tprg1l mutations in Xenopus laevis. Embryos injected with Tprg1l sgRNA and Cas9 mRNA displayed axis formation and convergent extension defects suggesting that ...


With Or Without You: Studying The Requirement Of P53 For Anti-Cancer Responses To Nuclear Export Inhibitors, Andrea E. Doak Jan 2016

With Or Without You: Studying The Requirement Of P53 For Anti-Cancer Responses To Nuclear Export Inhibitors, Andrea E. Doak

Undergraduate Honors Theses

Exportin-1 (XPO-1) is responsible for the movement of cargo proteins out of the nucleus and into the cytoplasm. Selective inhibitors of nuclear export (SINE) bind XPO-1 at cysteine-528, which results in the sequestration of cargo proteins in the nucleus. SINE drugs are currently being developed and tested in the treatment of many types of cancers. One of the cargos, p53 may play an important role in the efficacy of SINE. To test the necessity of p53 in the action of SINE drugs, matched pairs of cell lines with wildtype or functionally disrupted p53 were analyzed for differences in their cell ...


Effect Of Cmvil-10 On Exosome Production By Human Breast Cancer Cells, Susanna N. Basappa May 2015

Effect Of Cmvil-10 On Exosome Production By Human Breast Cancer Cells, Susanna N. Basappa

Undergraduate Honors Theses

Human cytomegalovirus (HCMV) is a ubiquitous virus that infects 70-90% of the general population, primarily the immunocompromised, but has been implicated in several forms of cancer, including breast cancer. Breast cancer is the second leading cause of cancer related deaths in women in North America, usually from metastasis. Exosomes are 30-100nm vesicles produced by most cells which carry protein and RNA to cells in their microenvironment. The aim of this study is to investigate the impact of HCMV-infection of a secreted viral cytokine, cmvIL-10, on exosome production by highly metastatic breast cancer cells.

MDA-MB-231 cells were cultured in vitro, and ...


The Role Of Histone Modifying Enzyme Suv420h2 In Pediatric Ependymoma., Sarah Goggin May 2015

The Role Of Histone Modifying Enzyme Suv420h2 In Pediatric Ependymoma., Sarah Goggin

Undergraduate Honors Theses

Cancer is the leading cause of non-accidental death in children. Pediatric ependymomas (PE) are the third most common brain tumor in children. Despite advances leading to better survival outcomes in some cancers, these tumors remain incurable in up to 45% of patients, with recurrent local relapse being the major cause of mortality[18, 19]. Surgical resection is currently the most effective treatment, but over 50% of children whose tumors have been totally resected will still experience tumor recurrence despite aggressive adjuvant therapy [22]. Key molecular events in the pathogenesis of PE have yet to be defined, and understanding these events ...


Cadmium Induced Transcription And Nfat/Cjun Proximal Promoter Binding In Breast Cancer Cells, Christopher Childers Jan 2015

Cadmium Induced Transcription And Nfat/Cjun Proximal Promoter Binding In Breast Cancer Cells, Christopher Childers

Undergraduate Honors Theses

In order to better comprehend onset and progression of diseases such as cancer, the means by which genes are regulated must be understood. RNA Polymerase II (Pol II) transcribes mRNAs that are translated into proteins, but this process is tightly controlled by transcription factors that recruit Pol II to promoter elements. These transcription factors determine if and when a gene is expressed at a basal level. This thesis focuses on the NFAT and AP-1 family of transcription activators. Each of these families has been characterized as important transcriptional activators in the onset and growth of cancer, but their mechanism of ...


The Bbc3 Antisense Intragenic Transcript, Bait, Contributes To Puma Expression By A P53-Autonomous Mechanism, Nicole C. Michael Jan 2015

The Bbc3 Antisense Intragenic Transcript, Bait, Contributes To Puma Expression By A P53-Autonomous Mechanism, Nicole C. Michael

Undergraduate Honors Theses

p53 is a tumor suppressor protein which orchestrates cell cycle arrest or apoptosis to prevent the hyperproliferation of cells which could lead to cancer. However, when p53 is inactivated, which happens in over 50% of cancers, it fails to induce PUMA, a potent apoptotic protein. Loss of PUMA makes cancer cells less likely to undergo apoptosis upon stress stimuli. Recent GRO-seq data revealed unique antisense transcription initiated 6kb into the PUMA locus, creating a small noncoding RNA transcript dubbed BAIT (BBC3 antisense intragenic transcript). This project focused on understanding the expression and function of BAIT, which we hypothesized could modulate ...


Mouse Polyomavirus T Antigens: Directors Of Cell Cycle Signaling, Catherine Nicholas Jan 2015

Mouse Polyomavirus T Antigens: Directors Of Cell Cycle Signaling, Catherine Nicholas

Undergraduate Honors Theses

Polyomaviruses (PyV) efficiently replicate by disrupting host cell signaling pathways. Disruption of the cell cycle is implicated in nearly all tumor formation. Studies of cellular transformation by primate PyV, SV40, and mouse polyomavirus (MPyV) have led to numerous findings concerning tumor suppressor proteins and cell cycle regulation pathways (Das D. and Imperiale 2009, Dahl et. al. 2005). Expression of PyV T Antigens (TAg) modifies signaling pathways and cell cycle checkpoints to the virus’ advantage. Expected modifications include inhibiting checkpoint proteins between G1 and S phases as well as promoting kinases with downstream signaling effects that result in progression to S ...


Evaluation Of Daily Oral Kinase Inhibitors In Pediatric Spnet Tumor Xenografts, Greg Heinicke Jan 2012

Evaluation Of Daily Oral Kinase Inhibitors In Pediatric Spnet Tumor Xenografts, Greg Heinicke

Undergraduate Honors Theses

Throughout the human body cells grow and die at different rates. Each tissue has specific cellular requirements that define the growth and death of its cells. For example red blood cells are replaced frequently whereas brain cells slowly die with age and are not replaced. Cancer comes from a fundamental breakdown in the regulation of growth. These new growing cells reach a point when they are too abundant. When they have surpassed the body's need for new cells, they form large masses called tumors. Tumors are deadly when they become malignant. Malignant cells have the ability to invade and ...


The Synthesis And Characterization Of Novel Ruthenium Terpyridine Complexes: Reactivity With Dna, Nicolette M. Jonkhoff Jan 2011

The Synthesis And Characterization Of Novel Ruthenium Terpyridine Complexes: Reactivity With Dna, Nicolette M. Jonkhoff

Undergraduate Honors Theses

Side effects associated with platinum-based anticancer therapies have resulted in the search for novel nonplatinum-based metal species. Among the different metal complexes generating interest, rutheniumII complexes have shown great potential as anticancer agents. A series of mixed ligand ruthenium complexes with he formula cis-[Ru(X)(HPB)(OH2)], where X corresponds to either (1) Terpy = 2,2':6',2"-terpyridine; (2) Pheterpy = 4' -Phenyl-2,2':6',2"-terpyridine or (3) Tterpy = 4'-Tolyl-2,2':6',2"-terpyridine, and HPB = 2-(2' -hydroxyphenyl)-benozoxazole, have been synthesized and structurally characterized. The DNA binding of the rutheniumII complexes has ...


The Effect Of Sex And Background On Doxorubicin-Induced Cardiotoxicity In Carbonyl Reductase 1 +/- Mice: A Comparative Study, Megan M. Freeland Jan 2009

The Effect Of Sex And Background On Doxorubicin-Induced Cardiotoxicity In Carbonyl Reductase 1 +/- Mice: A Comparative Study, Megan M. Freeland

Undergraduate Honors Theses

Doxorubicin has long been used clinically to treat a variety of cancers. Unfortunately, its success is limited due to its cardiotoxic side effects, restricting the cumulative dose that can be given to patients. It is known that the enzyme carbonyl reductase 1 (Cbr1) metabolizes this cancer drug in vivo, leading to the production of its toxic alcohol metabolite, doxorubicinol. A previous study has indicated that decreasing the expression level of carbonyl reductase 1 in male Cbr1+/- mice provided them with significant protection from doxorubicin-induced cardiotoxicity when compared to their wild type littermates. With the intent to identify whether the protection ...