Medicine and Health Sciences Commons^™

Computational Identification Of Noncoding Driver Mutations Based On Impact On Rna Processing, Kevin Zhu

Dissertations & Theses (Open Access)

Despite the prevalence of mutations in the noncoding regions of the DNA, their effects on cancer development remain largely uninvestigated. This is especially evident when compared to coding mutations, which have been relatively well-studied and, in certain cases, been identified as driver mutations for cancer. Recent studies, however, have identified noncoding mutations that frequently appear in certain types of cancer, which may be evidence that those mutations are important to cancer development. Nonetheless, the role of noncoding mutations in cancer remains unclear. A potential vector for understanding this mechanism is through observing the relation between noncoding mutations and functional RNA …

Improving Hpv Vaccination Series Initiation Rates And Compliance Among Indigent Women In South Texas, Ages 19-26, Through Provider Recommendation And Additional Clinic Funding: A Quality Improvement Project, Lacey Cudd

Doctor of Nursing Practice

The purpose of this quality improvement project was to increase human papillomavirus vaccination series initiation rates among indigent women, ages 19-26, at a clinic in South Texas. The human papillomavirus is a sexually transmitted infection that has been associated with multiple types of cancers. Each year, approximately 6.2 million cases of the human papillomavirus infection are diagnosed; as many as 75% of all new infections occur among females 18-26 years of age. The human papillomavirus vaccination has a high efficacy in regards to cancer prevention, preventing as many as 76% of cancers with only one dose. The project included educating …

The Role Of Pre-Existing Type 2 Diabetes Mellitus In Colorectal Cancer Stage And Survival In Elderly Americans: A Seer-Medicare Population-Based Study 2002-~2011, Sanae El Ibrahimi

UNLV Theses, Dissertations, Professional Papers, and Capstones

Diabetes is a common comorbid condition among colorectal cancer (CRC) patients, yet its effects in CRC outcomes, particularly stage at diagnosis, risk of death and variations by diabetes severity (complications vs no complications) and Hispanic ethnicity have not been adequately studied. The purpose of this study was to investigate the association between pre-existing T2DM and advanced stage at diagnosis in elderly patients with CRC; to examine whether diabetes is an independent predictor of poor survival from all-cause and CRC-specific mortality; to assess whether variations exist by diabetes severity and to analyze the outcomes for the Hispanic group.

The Surveillance Epidemiology …

Acculturation And Causes Of Death Among Filipinos In The Us: Focus On Cancer, Abegail Terso Reyes

UNLV Theses, Dissertations, Professional Papers, and Capstones

Filipinos in the US are 3.4 million, yet the main causes of death among this primarily immigrant population have not been well characterized nor compared with the mortality experience of their counterparts in the Philippines. Age-adjusted mortality rates were computed for the main causes of death for three populations: Filipinos living in the Philippines (FPHs), Filipinos living in California (FCAs), and non-Hispanic whites in California (WCAs). Regression-derived mortality rate ratios stratified by sex were used to compare the populations, using WCA as the referent population. Included causes of death were ischemic heart disease, stroke, cancer and chronic lower respiratory disease, …

Targeting The Major Regulator Of Mitosis., J. Mason Hoffman

Electronic Theses and Dissertations

Mitosis-inhibiting chemotherapeutics (e.g. taxanes) are frequently used to treat multiple cancer types. Recently, there has been much concern about the limited success of these drugs due to resistance and a lack of molecular targets. Thus, there is high demand for new drugs with diverse cellular targets. Targeting the regulators of mitosis is a promising approach. The anaphase promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle progression at multiple points. The interaction of ANAPC2 and ANAPC11, catalytic core subunits, is necessary for APC/C function. An in silico approach was used to identify compounds predicted to prevent assembly …

Developing A Peer Cancer Support Group Evaluation, Glenda Kith

Master's Projects and Capstones

Introduction: For many years, health care organizations have offered peer cancer support groups to cancer survivors, but peer cancer support group evaluation is not standardized. Without a clear and consistent evaluation, it may be difficult to understand the efficacy of and gain support for peer cancer support groups. In this paper, I discuss how an evaluation was created for a peer cancer support group called Cancer Awareness Resource and Education (CARE).

Methods: In-depth interviews with CARE participants were conducted and pre-survey and a post-survey were developed. The in-depth interviews included a convenience sample of eight individuals, two individuals from the …

Influence Of Socioeconomic Status On Event-Free Survival In Children Diagnosed With Acute Lymphoblastic Leukemia, Jordan L. Chester

Masters Theses

Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children. However, little is known about how socioeconomic status (SES) influences the outcomes of children diagnosed with ALL. The goal of the research study was to understand how SES impacted the outcomes of children diagnosed with ALL, with a particular interest in children living in West Michigan. Children ages 0-14 years who received treatment for ALL at Spectrum Health’s Helen DeVos Children’s Hospital’s Pediatric Hematology and Oncology program between the years 2002-2011 were considered for this study. Eligible participant’s zip codes and dates of relapse/death were obtained …

Meta-Regression: Prognostic Models As Objective Predictors Of Mortality Among Icu Cancer Patients, Sheila Donnell

Nursing Theses and Dissertations

Cancer patients admitted to the intensive care unit (ICU) may be experiencing complications of disease or treatment-related effects. While acute complications related to disease and/or its therapeutic management vary in severity, the approach to ICU-centered care is complicated by actual versus perceived risks of poor outcomes. Prognostic models that inform clinical judgment of nurses and physicians may prove helpful in this population. The Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) are ICU-based models predicting 30-day mortality among the general ICU population. Although studies have been …

Angiogenesis And Neo-Microcirculatory Function In Diseased Tissue Revealed By Intravital Microscopy, Giovanni-Michele Arpino

Electronic Thesis and Dissertation Repository

Angiogenesis is the process of generating new blood microvessels. In adults, angiogenesis is fundamental to tumor biology and also to tissues rendered ischemic from vascular occlusion. Despite a promising appeal, strategies designed to simulate or otherwise modify the angiogenic process in adult tissues have yet to realize significant therapeutic potential. Importantly, understanding the structure and function of new microvascular networks formed in adult, diseased tissues is limited. In fact, it remains unknown if a new or regenerated microcirculation can effectively deliver oxygen to the tissue. The purpose of this thesis was to seek out novel determinants of functional angiogenesis and …

Metabolic Regulation Of Cellular Signaling, Rashid John Darbandi

Theses and Dissertations (ETD)

Using the biochemically tractable Xenopus oocyte model system, we have previously characterized a novel metabolic regulation of cell death. We found that glucose-6-phosphate (G6P) via the pentose phosphate pathway leads to increased nicotinamide adenine dinucleotide phosphate (NADPH) levels, a subsequent increase in cytosolic acetyl-coenzyme A and activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). We recently identified coenzyme A (CoA), derived from the breakdown of acetyl-CoA, as the key metabolic signal that mediates a novel mechanism of calmodulindependent activation of CaMKII. CoA binds directly to the calmodulin (CaM) binding domain (CaMBD) of CaMKII resulting in its activation and downstream inhibitory phosphorylation …

Clinical And Therapeutic Significance Of Obesity In Melanoma, Jennifer L. Mcquade

Dissertations & Theses (Open Access)

While the FDA approval of targeted and immune therapies in metastatic melanoma (MM) have dramatically improved outcomes in this disease, de novo and/or acquired resistance can limit the clinical benefit of these agents. The IGF-1/PI3K/AKT pathway has been implicated in resistance to both targeted and immune therapy. The IGF-1/PI3K/AKT pathway has also been shown to play a key role in the pathogenesis of obesity in other malignancies. To date, the impact of energy balance on clinical outcomes and therapeutic response in MM has not been studied. I hypothesized that energy balance would impact the molecular biology, behavior, and drug sensitivity …

Rna Sequencing In The Development Of Cancer-Cachexia, Thomas Allen Blackwell

Graduate Theses and Dissertations

Introduction: Cancer is a major public health problem in the U.S. and the world. In 2013 there were an estimated 1,660,290 new cases of cancer in the U.S. Cancer-Cachexia (CC) is a common effect of many cancers, and is directly responsible for 20-40% of cancer-related deaths. The mechanisms that control the development of CC are not well understood. Most investigations of CC focus on the post-cachectic state and do not examine the progression of the condition. The purpose of this study was to utilize RNA sequencing to analyze transcriptomic alterations throughout the progression of CC. Methods: Lewis Lung Carcinoma cells …

Prostate Cancer In African American Men, Chinwe Egwudo

Nursing Student Class Projects (Formerly MSN)

Prostate cancer, a malignancy with racial disparity, affects African American men more than Caucasians or any other race.

Cervical Cancer, Mary Jedlicka

Nursing Student Class Projects (Formerly MSN)

No abstract provided.

Mk2 Promotes Colorectal Cancer Development, Invasion, And Growth Through Mk2-Induced Cytokines, Anita Lynne Ray

Biomedical Sciences ETDs

Colorectal cancer (CRC) is the third most common malignancy in the United States for men and women. A major risk factor for CRC development and progression is inflammation, in particular the inflammatory cytokines IL-1, IL-6, and TNF-α. These proteins promote critical cancer functions, such as proliferation, invasion, survival, and migration. Control of inflammation is one potential area of therapeutic intervention for some cancers. Because signaling of these cytokines overlaps in many of the same pathways, targets upstream of protein production could prove an effective strategy to reduce inflammation. MAPK-activated protein kinase 2 (MK2) pathway controls production of these cytokines within …

African American Men's Prostate Cancer Knowledge And Self-Efficacy For Informed Decision-Making: A Mixed Methods Study, Dionne J. Jones-Dendy Phd

Nursing Theses and Dissertations

A mixed methods study was conducted whereby, the quantitative portion has a randomized control design, in an urban Delaware community to examine the effectiveness of an educational intervention, which included the testimony of an African American (AA) prostate cancer survivor on AA men’s (n=98) prostate cancer knowledge and self-efficacy for informed decision making. Guided by Bandura’s Social Cognitive theory, participants’ prostate cancer knowledge measured by PROCASE and for self-efficacy measured by the Prostate Cancer Screening Self-efficacy scale, were evaluated before and following viewing of the American Cancer Society’s prostate cancer video. Participants randomized to the intervention completed evaluations after the …

Impact Of Hpv Education On Knowledge, Perception, And Cultural Influence Among African American Parents, Christina Lattner

College of Science and Health Theses and Dissertations

Background: Infection with human papillomavirus (HPV), the sexually transmitted virus that causes cervical and penial cancer can be prevented. An effective vaccine has been approved for both boys and girls since 2006. Despite recommendation from the Center of Disease Control, vaccination initiation and completion rates among African American adolescents in the United States are lower than average in the nation.

Objectives: The purpose of this descriptive survey study was to identify African-American parents’ knowledge and perceptions of sexually transmitted HPV infection and the HPV vaccination. The secondary objective was to use a single-group pre-test post-test research design to examine …

Breast Cancer Patient Preparedness For Transition To Survivorship: Individualized Survivorship Care Plans, Kimberly Beringer

Master's Projects and Capstones

Purpose. For breast cancer survivors, after-effects of surgery, radiation and chemotherapy can be substantial, and recurrence is a concern requiring constant surveillance. National healthcare organizations have promulgated guidelines that include providing individualized survivorship care plans (SCP’s). At a northern California oncology department, SCP’s will be prepared for breast cancer patients and delivered in-person by the oncology nurse navigator (ONN).

Method. The author worked with the ONN to develop the format and content requirements for the SCP’s. The ONN prepared individualized plans for patients and scheduled in-person appointments to deliver the SCP’s. A feedback survey to assess preliminary impact was then …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck

Arts & Sciences Electronic Theses and Dissertations

Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …

One-Pot Syntheses And Characterizations Of “Click-Able” Polyester Polymers For Potential Biomedical Applications, James F. Beach Ii

Electronic Theses & Dissertations

In this study, a synthetic polyester polymer was designed using polyethylene glycol, sorbitol, glutaric acid and 4-pentynoic acid as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by Novozyme-435, an enzyme suitable for polyesterification of biocompatible compounds. The progress of the reaction was monitored with respect to time and vacuum exposure, with samples being subjected to standard characterization protocols. Polymers with high molecular weight and water solubility were chosen for further modification into folate-functionalized polymeric nanoparticles for targeted drug delivery to cancer cells. This was achieved by employing a solvent diffusion method, wherein the polymer …

The Healing Power Of A Whole Foods, Plant-Based Diet: A Nutrition Prescription For Cancer, Meghan Adelman Mrs.

Master's Projects and Capstones

Chronic disease is quickly overtaking infectious diseases as one of the biggest threats to population health worldwide (Egger, 2012). Studies have shown that plant based diets are effective at reducing prevalence but are also a viable complimentary treatment approach to healing. Further investigation is needed into how plant based diets can reduce risk of recurrence, specifically as it relates to a cancer diagnosis. The Ceres Project is an organization that provides a healing foods philosophy to the care of cancer patients through meal delivery programs at low to no cost. The aim of this research study was to implement the …

The Effects Of Lipocalin 2 On Lung Metastasis Of Colorectal And Other Cancers, Lauren Strzyzewski

Senior Theses

Lipocalin 2 (Lcn2) is a member of the lipocalin family of siderophore-binding molecules that can mediate iron trafficking. It acts during the innate immune response and has been implicated in conflicting roles in metastasis, leaving its role undefined. In breast cancer LCN2 was shown in previous studies to both inhibit or promote metastasis. Previous studies the Pena laboratory showed that increasing the serum levels of LCN2 caused a significantly increase in liver metastasis of the poorly metastatic MC-38 colon cancer cell line. In this study, we examined the ability of LCN2 to promote metastasis of colon and other cancers to …

Managing Variant Discrepancy In Hereditary Cancer: Clinical Practice, Barriers, And Desired Resources, Ellen Zirkelbach

Dissertations & Theses (Open Access)

Variants are changes in the DNA whose phenotypic effects may or may not be definitively understood. Because variant interpretation is a complex process, sources sometimes disagree on the classification of a variant, which is called a variant discrepancy. This study aimed to determine the practice of genetic counselors regarding variant discrepancies and to identify the barriers to counseling a variant discrepancy in hereditary cancer genetic testing. This investigation was unique because it was the first to address variant discrepancies from a clinical point of view. An electronic survey was sent to genetic counselors in the NSGC Cancer Special Interest Group. …

An In Vitro Study On The Detection Of Ovarian Cancer Using A Novel Ph-Specific Targeting Polypyrrole Nanocontrasting Agent., Phillip Chuong

College of Arts & Sciences Senior Honors Theses

Longitudinal tracking and accumulation of polymeric nanoparticles in the context of cancer has largely occurred through identification of a fluorescent cargo. In this study, we created a dual extracellular acidic pH targeted polypyrrole-based hollow nanoparticle as a theranostic (maintain both therapeutic and diagnostic capabilities) agent for improved detection and treatment of ovarian cancer. Polypyrrole-hollow nanospheres (PPy-CS) were fabricated through the removal of a silver chloride (AgCl) core, which served as a template, followed by coating with chitosan and further tumor targeted with a pH low insertion peptide, V7. We exploited the NIR-absorbing property of polypyrrole to track both the nanoparticle …

Peptide Vaccine Formulation Controls The Duration Of Antigen Presentation And Magnitude Of Tumor‐Specific Cd8+ T Cell Response, Hiep Khong

Dissertations & Theses (Open Access)

Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that the duration of antigen presentation critically affected the quantity and quality of T cell response and subsequent anti‐tumor efficacy. Here we describe L‐tyrosine amino acid‐based microparticles as a novel peptide vaccine adjuvant for the induction of tumor‐specific T cells. L‐tyrosine microparticles did not induce inflammasome activation, but instead extended antigen presentation time. The consequent prolongation in antigen presentation translated into prolonged T cell proliferation and superior numbers and anti‐tumor function of vaccination‐induced CD8+ T cells. Indeed, prolonging antigen presentation by repeated injection …

Genome-Scale Precision Proteomics Identifies Cancer Signaling Networks And Therapeutic Vulnerabilities, Hong Wang

Theses and Dissertations (ETD)

Mass spectrometry (MS) based-proteomics technology has been emerging as an indispensable tool for biomedical research. But the highly diverse physical and chemical properties of the protein building blocks and the dramatic human proteome complexity largely limited proteomic profiling depth. Moreover, there was a lack of high-throughput quantitative strategies that were both precise and parallel to in-depth proteomic techniques. To solve these grand challenges, a high resolution liquid chromatography (LC) system that coupled with an advanced mass spectrometer was developed to allow genome-scale human proteome identification. Using the combination of pre-MS peptide fractionation, MS2-based interference detection and post-MS computational interference correction, …

Sensitivity Of Diffuse Reflectance Spectroscopy To Dose- And Depth-Dependent Changes In Tumor Oxygenation After Radiation Therapy, Daria Semeniak

Graduate Theses and Dissertations

Along with chemotherapy, immunotherapy, and surgery, radiotherapy is one of the most common treatments used against cancer. Around 50% of all cancer patients undergo radiation therapy. While for some patients radiotherapy works efficiently and lead to a complete cancer disappearance, for others treatment outcome may be less favorable due to radioresistance processes happening within a tumor on the molecular level. Radioresistance remains a big challenge for modern oncology. The ability to identify radioresistance at the early stage of radiotherapy would help physicians to improve therapy efficiency. At the current moment, despite the rapid progress in cancer understanding and diagnostic modalities, …

Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan

Undergraduate Research Symposium Posters

Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are found in about 23% of acute myeloid leukemia (AML) samples and about 90% of gliomas. Mutations result in neomorphic function of the IDH enzyme that yields the novel molecule 2-hydroxyglutarate (2HG) instead of alpha-ketoglutarate (aKG). 2HG is known to be associated with hypermethylation of DNA and histones, a phenotype seen in AML. Our lab intends to study the mechanism by which hypermethylation is achieved and how this mechanism relates to the onset of cancer. In this experiment, we utilized a line of H9 stem cells which we had developed. These cells …

Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett

Undergraduate Honors Theses

Pyrrolobenzodiazepines (PBDs) are a group of naturally occurring compounds that were discovered in the cultures of Streptomyces in the 1960s. Some natural PBDs discovered in these cultures, such as anthramycin and sibiromycin, were shown to possess a broad spectrum of anti-tumor activity. Since cancer is still a leading cause of death globally, the development of novel anti-proliferative derivatives of PBDs is essential for human welfare worldwide. Further synthesis and structure-activity relationship (SAR) studies of the parent natural products and their tetracyclic analogs will lead to the discovery of drug candidates. In this work, thirteen PBD analogues were synthesized using no …