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Full-Text Articles in Cancer Biology

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 ...


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 ...


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 ...


Responses To Ionizing Radiation And Translation Inhibition In Drosophila Melanogaster And Human Cancer Cells, Stefanie Michaela Stickel Jan 2014

Responses To Ionizing Radiation And Translation Inhibition In Drosophila Melanogaster And Human Cancer Cells, Stefanie Michaela Stickel

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

A common regimen for the treatment of solid tumors includes ionizing radiation (IR), chemotherapies, and targeted agents, such as kinase inhibitors. Cancer therapies have been traditionally tailored to the tissue origin of the tumor, rather than the mutation type; however, this concept has been changing with evidence that agents targeted to specific mutations are effective in many cancer types. The latter theory assumes that inhibition of the oncogenic mutation trumps differences between tissues, a concept that has never been proven in a whole organism. My results in the first half of this thesis show for the first time that isogenic ...


Identifying Purification And Storage Techniques For The Human Papillomavirus Type 16 Major Capsid Protein L1, Stephanie Anderson Apr 2012

Identifying Purification And Storage Techniques For The Human Papillomavirus Type 16 Major Capsid Protein L1, Stephanie Anderson

Molecular, Cellular, and Developmental Biology Undergraduate Contributions

Expression of human papillomavirus (HPV) major capsid protein L1 in Escherichia coli produces L1 proteins that can self­assemble into pentamers, with 72 pentamers forming a capsomere. With effective purification and storage techniques, these L1 pentamers could provide a more economic alternative for manufacturing HPV vaccines. Various techniques were evaluated in order to develop the most efficient method for L1 protein purification. Primary purification of L1 protein fused to Glutathione S­ transferase (GST) was accomplished by GST affinity chromatography. DEAE anion exchange chromatography and heparin affinity chromatography were then tested as secondary purification techniques. Results showed heparin chromatography removed L1 ...