Translational Medical Research Commons^™

Immunotherapy Of Cancer: Reprogramming Tumor/Immune Cellular Crosstalk To Improve Anti-Tumor Efficacy, Kyle K. Payne

Theses and Dissertations

Immunotherapy of cancer has been shown to be promising in prolonging patient survival. However, complete elimination of cancer and life-long relapse-free survival remain to be major challenge for anti-cancer therapeutics. We have previously reported that ex vivo reprogramming of tumor-sensitized immune cells by bryostatin 1/ionomycin (B/I) and the gamma-chain (γ-c) cytokines IL-2, IL-7, and IL-15 resulted in the generation of memory T cells as well as CD25+ NKT cells and CD25+ NK cells. Adoptive cellular therapy (ACT) utilizing these reprogrammed immune cells protected FVBN202 mice from tumor challenge, and overcame the suppressive functions of myeloid-derived suppressor cells (MDSCs). We then …

Meta-Analysis Of Gene Expression Studies, Umaporn Siangphoe

Theses and Dissertations

Combining effect sizes from individual studies using random-effects models are commonly applied in high-dimensional gene expression data. However, unknown study heterogeneity can arise from inconsistency of sample qualities and experimental conditions. High heterogeneity of effect sizes can reduce statistical power of the models. We proposed two new methods for random effects estimation and measurements for model variation and strength of the study heterogeneity. We then developed a statistical technique to test for significance of random effects and identify heterogeneous genes. We also proposed another meta-analytic approach that incorporates informative weights in the random effects meta-analysis models. We compared the proposed …

Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui

Dissertations and Theses (Open Access)

Background: Chronic stress and sustained adrenergic signaling are known to promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.

Materials and Methods: ADRβ expression levels were examined in patient-derived cervical cancer samples. We used an orthotopic model of cervical cancer to investigate the effects of restraint stress on tumor growth and metastasis. We evaluated the in vivo effects of a β-blocker, propranolol, and HPV E6/E7 siRNA. In vitro, ADRβ positive cervical cancer cells were …

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear …

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica E. Reyes

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear …

Targeting The Mdm2-P53 Axis For The Treatment Of Dedifferentiated Liposarcoma, Katelynn Bill

Dissertations and Theses (Open Access)

Dedifferentiated liposarcoma (DDLPS) is an aggressive malignancy characterized by a high rate of recurrence and dismal patient outcome. Minimal improvement in patient survival has been made in the last several decades, highlighting the crucial need for improved therapeutic strategies. A better understanding of the molecular deregulations underlying DDLPS would facilitate the discovery of improved therapeutic approaches. MDM2 is a well characterized oncoprotein and the most known negative regulator of p53. MDM2 amplification is considered the “hallmark” of DDLPS. Additionally, these tumors are known to harbor wild-type p53. We sought to take advantage of this knowledge and evaluate the role of …

How To Lie With (Fda) Statistics, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

The FDA approved 27 new drugs in 2013. Is this a downward trend? Is it an upward trend? Does it suggest that the pharmaceutical industry is failing, or that genomics is finally paying dividends? We revisit Darrell Huff’s 1954 classic How to Lie with Statistics for insights into these pressing questions.

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Brain Blast 2014 Poster, Annie Leslie

Brain Blast

Announcement poster for UNE's Brain Blast 2014, a pechakucha-style brain health and safety awareness and learning event.

Brain Blast 2014 Speakers Poster, Annie Leslie

Brain Blast

Poster from UNE's Brain Blast 2014 listing the presenters at this event.

Receptor Of Advanced Glycation Endproducts (Rage) Is Positively Correlated With Tumor Necrosis Factor-Α In Adolescents With Obesity, Tasnim Rahman, Daniel H. Conrad, Anshu Gupta

UROP Posters

Introduction: Obesity in childhood is associated with an increased prevalence of diabetes and other traditional cardiometabolic risk factors, suggesting an epidemic of premature cardiovascular disease among today’s youth. Glycotoxins, known as advanced glycationend products (AGE’s), activating via the membrane-bound receptors (mRAGE), have been implicated in the pathophysiology of inflammation, (increased tumor necrosis factor-α [TNF-α ]), insulin resistance and vascular dysfunction in adults, but the role of RAGE in the early stages of metabolic disorders is unknown. In this study, we assessed relationship of cardiometabolicrisk factors, mRNA expression of TNF-α and RAGE in peripheral monocytes in adolescents with obesity.

Methods: Thirty …

Sildenafil And Celecoxib Interact To Kill Breast Cancer Cells, Brittany Binion

Theses and Dissertations

Breast cancer is the second most commonly diagnosed cancer among American women and is responsible for the second highest number of cancer-related deaths. Targeted therapeutic agents sildenafil, a phosphodiesterase type 5 inhibitor, and celecoxib, a cyclooxygenase-2 inhibitor, have been used individually in conjunction with other chemotherapeutic agents to enhance cell killing in a variety of cancers. Sildenafil when combined with traditional chemotherapeutic drugs, such as the taxanes and anthracyclines, or celecoxib combined with traditional hormone therapies have been used to increase cytotoxicity and cell killing. The data presented here demonstrates that the novel combination of sildenafil and celecoxib work together …

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

Expert–Novice Differences In Mental Models Of Viruses, Vaccines, And The Causes Of Infectious Disease, Benjamin D. Jee, David H. Uttal, Amy N. Spiegel, Judy Diamond

World of Viruses

Humans are exposed to viruses everywhere they live, play, and work. Yet people’s beliefs about viruses may be confused or inaccurate, potentially impairing their understanding of scientific information. This study used semi-structured interviews to examine people’s beliefs about viruses, vaccines, and the causes of infectious disease. We compared people at different levels of science expertise: middle school students, teachers, and professional virologists. The virologists described more entities involved in microbiological processes, how these entities behaved, and why. Quantitative and qualitative analyses revealed distinctions in the cognitive organization of several concepts, including infection and vaccination. For example, some students and teachers …

Going Viral, Judy Diamond

World of Viruses

Science education is developing new and innovative means of communication that compete directly with global media to reach the ‘YouTube Generation’. The truly interdisciplinary team of the SEPA-funded World of Viruses project is discovering how best to spread the word.

KEY COLLABORATORS
Judy Diamond, Professor, University of Nebraska State Museum
Charles Wood, Director, Nebraska Center for Virology
Moira Rankin, President, Soundprint Media Center, Inc
Carl Zimmer, Science writer and author of WoV book of essays, A Planet of Viruses
David Uttal, Cognitive science professor, Northwestern University
Benjamin Jee, Cognitive scientist, College of Holy Cross
Tom Floyd, Comic illustrator, Nebraska Educational …