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Epigenetic Regulation Of Nuclear Hormone Receptor Dax-1, Michael B. Heskett

Master's Theses

DAX-1 (NR0B1) is an orphan nuclear receptor that plays a key role in the development and maintenance of steroidogenic tissue in mammals. Dax-1 is also expressed in mouse embryonic stem (ES) cells and is required to maintain pluripotency. Duplication of the X-chromosome in the region containing the NR0B1 gene results in sex reversal, and mutations in NR0B1 cause adrenal hypoplasia congenita. DAX-1 has been observed to act as a corepressor of other nuclear receptors including androgen receptor (AR), estrogen receptor (ER), and steroidogenic factor 1 (SF-1). In addition to pluripotent ES cells, DAX-1 is primarily expressed in select tissues of …

A Four-Dimensional Image Reconstruction Framework For Pet Under Arbitrary Geometries, Aswin John Mathews

McKelvey School of Engineering Theses & Dissertations

Positron Emission Tomography (PET) is a functional imaging modality with applications ranging from the treatment of cancer, studying neurological diseases and disease models. Virtual-Pinhole PET technology improves the image quality in terms of resolution and contrast recovery. The technology calls for having a detector with smaller crystals placed near a region of interest in a conventional whole-body PET scanner. The improvement is from the higher spatial sampling of the imaging area near the detector. A prototype half-ring PET insert built to study head-and-neck cancer imaging was extended to breast cancer imaging. We have built a prototype half-ring PET insert for …

Design And Development Of A Novel Class Of Cell Cycle Cdk Inhibitors Targeting The Cyclin Binding Groove Utilizing The Replace Strategy, Padmavathy Nandha Premnath

Theses and Dissertations

Inhibition of CDK2 activity in G1 and S phases of the cell cycle can promote selective apoptosis of cancer cells through the E2F1 pathway. Currently available CDK inhibitors target the ATP binding pocket and result in lack of specificity for the cell cycle vs. the transcriptional CDKs. It has been shown that a peptide HAKRRLIF derived from the tumor suppressor p21 binds to the cyclin binding groove (CBG) and selectively inhibits cell cycle CDKs (CDK2/Cyclin A, CDK2/Cyclin E and CDK4/Cyclin D). The CBG is unique to cell cycle CDKs hence targeting this site avoids the inhibition of transcriptional CDKs can …

A Three-Dimensional-Engineered Matrix To Study The Microenvironment Of Cancer Stem Cells, Samaneh Kamali Sarvestani

Theses and Dissertations

Maintenance of cancer stem cells (CSCs) is regulated by their microenvironment. As cancer cells are affected by many factors in their microenvironment, a major challenge is to isolate the effect of a specific factor on CSCs while keeping other factors unchanged. We developed a synthetic inert 3D Poly Ethylene Glycol Di-Acrylate (PEGDA) gel culture system as a unique tool to study the effect of microenvironmental factors on CSCs response. Synthetic hydrogels provide the flexibility to design three-dimensional (3D) matrices to isolate and study individual factors in the tumor microenvironment. The first objective of this work was to investigate the effect …

Novel Insights Into The Role Of The Smoothened Cysteine Rich Domain In Hedgehog Signalling, Rajashree Rana

Theses and Dissertations (ETD)

The Hedgehog (Hh) signal transduction pathway functions as one of the key developmental pathways and deranged Hh signalling is associated with numerous cancer and tumor conditions. The Smoothened (Smo) G protein coupled receptor (GPCR) functions as the signal transducer of the Hh pathway and is the most attractive drug target of the pathway. The structure of the Smo receptor includes seven membrane spanning domains, extracellular and intracellular loops connecting the membranous domains and the extracellular cysteine rich domain (CRD). The extracellular CRD of the Smo receptor is homologous to the Frizzled (FzD) CRD. The FzD CRD interacts with the physiological …

Identification Of Cell Signaling Pathway Regulated By Micrornas In Cancer Cells Using A Systems Biological Approach, Sangbae Kim

Dissertations & Theses (Open Access)

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression via imperfect binding of the miRNA to specific sites in the 3' untranslated region of the mRNAs. Because prediction of miRNA targets is an essential step for understanding the functional roles of miRNAs, many computational approaches have been developed to identify miRNA targets. However, identifying targets remains challenging due to the inherent limitation of current prediction approaches based on imperfect complementarity between miRNA and its target mRNAs. To overcome these current limitations, we developed a novel correlation-based approach that is sequence independence to predict functional targets of miRNAs by …

Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee

Dissertations & Theses (Open Access)

Cancer cells display dramatic alterations in cellular metabolism to meet their needs of increased growth and proliferation. In the last decade, cancer research has brought these pathways into focus, and one emerging issue that has come to attention is that many oncogenes and tumor-suppressors are intimately linked to metabolic regulation (Jones and Thompson, 2009). One of the key tumor-suppressors involved in metabolism is Liver Kinase B1 (LKB1). LKB1 is the major upstream kinase of the evolutionarily conserved metabolic sensor—AMP-activated protein kinase (AMPK). Activation of the LKB1/AMPK pathway provides a survival advantage for cells under energy stress. LKB1 forms a heterotrimeric …

Lung Cancer Survival Disparities In Nevada, Chima Osuoha

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lung cancer is the leading cause of cancer death in both men and women in the United States. Nevada shows moderate incidence rates of lung cancer for men but high rates for women. Little is known about the lung cancer experience and survival characteristics of the nearly 2000 new cases occurring every year in the State. The purpose of this study was to measure the extent to which geographic area of residency, gender, race, health insurance, social economic status (SES) and stage at diagnosis were associated with survival in patients diagnosed with lung cancer in Nevada. This was a retrospective …

Effect Of Chemotherapeutic Treatment Schedule On A Tissue Transport Model, Dan E. Ganz

Masters Theses

Current chemotherapeutic treatment schedule prediction methods rely heavily on PK/PD-based models and overlook the important contribution of tissue-level transport and binding. Tissue-level transport and binding phenomena are essential to understanding drug delivery and efficacy in tumors. Drugs with desirable PK/PD properties often fail in vivo due to poor tissue-level transport. We developed an in silico method to predict the effect of treatment schedule on efficacy that couples PK/PD with tissue-level transport. Treatment schedules were implemented on theoretical drugs with different PK/PD and transport properties. For each drug with a given clearance rate, diffusivity, and binding, treatment schedules consisting of one …

Designing A Pore-Forming Toxin Cytolysin A (Clya) Specific To Target Cancer Cells, Alzira Rocheteau Avelino

Masters Theses

Cytolysin A (ClyA) is a member of a class of proteins called pore-forming toxins (PFTs). ClyA is secreted by Gram-negative bacteria, and it attacks a number of mammalian cells by inserting into and forming channels within the cell membrane (Oscarsson J et al., 1999). It has been suggested that ClyA binds to cholesterol (Oscarsson J et al., 1999) and thus can insert into the membranes of many different cell types of eukaryotic origin. In our studies we propose to engineer a ClyA protein that can only attack a small subset of cell types. We propose to engineer ClyA that can …

Temperature And Ph Imaging Using Chemical Exchange Saturation Transfer (Cest) Mri Contrast, Nevin Neil Campbell Mcvicar

Electronic Thesis and Dissertation Repository

Chemical exchange saturation transfer (CEST) is a novel mechanism used to generate contrast in magnetic resonance imaging (MRI). Recently, CEST contrast was proposed to noninvasively measure physiological parameters including temperature and pH. Tissue temperature and pH are known markers of pathological processes in many diseases including stroke and cancer. CEST contrast can be generated using endogenous proteins and peptides (endogenous CEST) or using exogenous paramagnetic lanthanide agents (PARACEST).

The general problem of optimizing applications of endogenous CEST and PARACEST contrast to measure temperature and pH is addressed in this thesis. Highlights of the thesis include a novel application of PARACEST …

Design Of A Targeted Bacterial Drug Delivery Vector For The Treatment Of Cancer And Metastases, Charles Alexander Swofford

Doctoral Dissertations

Engineered Salmonella possess unique capabilities that make them ideal drug delivery vectors for tumors. Targeted bacterial delivery of anticancer proteins has the ability to overcome therapeutic resistance in tumors that limits the efficacy of chemotherapeutics. In my doctoral research, I identified a protein-drug that can be expressed by bacteria and rapidly kills cancer cells. I also created a density dependent switch that initiates gene expression in tumors and prevents expression in healthy tissue. Combining these two systems has created a potent anti-cancer system that targets tumors with minimal toxicity. I cloned genes for five potential anti-cancer proteins into Salmonella. …

Design And Synthesis Of Small-Molecule Inhibitors Of The Hypoxia Inducible Factor-1 As Anticancer Therapeutics, Zeus Allen O. De Los Santos

Chemistry Theses

Throughout history, cancer has been severely plaguing mankind; the search for a

cure to cancer had long been sought by scientists and still poses as one of the

greatest challenges scientists have yet to overcome. Hypoxia in cells is a condition

where there is little to no oxygen availability in its environment. In general, this event

is detrimental since this can lead to cell necrosis or reoxygenation injuries. However,

hypoxia, a prominent property of most solid tumors, activates the hypoxia-inducible

factor (HIF-1) family of transcription factors that promotes angiogenesis. In this

study, we describe the design and synthesis of small-molecule …

An Assessment Of Selected Factors Associated With Hpv Vaccination Completion Among The African American Adolescents In United States: 2012 National Immunization Survey - Teen, Vaishali Sahu

Public Health Theses

Background: Human Papillomavirus is the most common STI in United States and is most prevalent among the adolescents and young adults. HPV causes cervical, anal, vulvar, vaginal, penile, oropharyngeal cancers and ano-genital warts. Certain populations are found to be at higher risk such as African Americans. 3 doses of HPV vaccine are recommended to adolescents before sexual debut to immunize against HPV. The purpose of this study was to assess the factors associated with the completion of 3 dose HPV vaccination series particularly among the African American adolescents.

Methods: National Immunization Survey – Teen 2012 data was used to assess …

Geographic Disparities In Cancer Mortality To Incidence Ratios, Kyle Buck

Theses and Dissertations

While cancer rates have shown promising trends over the last few decades, not all populations have experienced the same levels of decrease in cancer incidence in mortality rates. Identifying populations suffering from the impacts of the disparities has become a major goal in cancer research.

Most research has focused on the influence of single variables on cancer disparities or on small-scale case studies. Using the information from these analyses, the research conducted in this dissertation tests the relationship of selected variables to an outcome measure, the mortality to incidence ratio (MIR) in search of spatial relationships between the indicators and …

Role Of Chronic Inflammation On Liver Function During Cachexia Progression In The ApcMin/+ Mouse Model, Aditi Narsale

Theses and Dissertations

Cachexia is a multifactorial syndrome that manifests during the advanced stage of chronic diseases and is characterized by a progressive loss of body mass sustained by underlying inflammation. The ApcMin/+ mouse is an established model of cachexia that exhibits a gradual loss of body mass correlating with increasing tumor burden and plasma IL – 6 levels. Moreover it also mimics other secondary characteristics observed in cachectic patients like splenomegaly, elevated plasma endotoxin levels, gut barrier dysfunction, hypogonadism and an overall hypermetabolic state. Liver controls the energy metabolism in the body by regulating glucose and lipid metabolism, glycogen storage, filtration of …

New Insights In The Regulation Of Mitochondrial Functions And Metabolic Reprogramming By Erbb Receptors In Cancer, Nirav Patel

Open Access Dissertations

Dysregulation of ERBBs signaling has been known to be responsible for several types of tumors including breast, ovary, lung, pancreas, prostate and more. Functions of ERBB receptors are mainly known from its overexpression in cancers. Apart from elevated levels of ERBB receptors, low levels of ERBB signaling also play a crucial role in normal development and maintenance of mammalian organs. However, the role of signaling by the low “normal” levels of ERBB receptors is poorly understood. Altered ERBB signaling has been implicated with several cardiac defects. One of the severe side effects of ERBB2-targeted therapy in breast cancer patients is …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations & Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

Selection Of A Nanoparticle Stabilizer For A Calcium Phosphate Drug Delivery System, Jessica L. Woodman

Doctoral Dissertations

Overall cancer survival rates steadily decline each year following diagnosis and side effects of chemotherapy restrict its use. The chemotherapeutic cis-diamminedichloro-platinum (cisplatin, CDDP) is poorly soluble and has dose limiting side effects. Nanoparticle delivery systems can deliver a higher dose of drug directly to the tumor by both active and passive targeting, holding promise of fewer side effects and greater anti-tumor efficacy. To date, few nanoparticle systems have been FDA approved for the treatment of cancer due to complicated physicochemical characterization, drug inactivation by the delivery system, scale-up challenges, and lack of demonstrated in vivo safety and efficacy. Further research …

Women's Stories Of Breast Cancer: Sharing Information Through Youtube Video Blogs, Jenna Kressler

Electronic Thesis and Dissertation Repository

Breast cancer is one of the most prevalent chronic diseases among North American women. Individuals need accessible and reliable health information for self-care and self-health promotion. Increasingly, individuals are contributing to and accessing information about cancer, using interactive online resources such as YouTube. The purpose of this research was to investigate the personal YouTube video blogs of women with breast cancer and their portrayed messages. This study used a narrative inquiry to examine the video blogs of four women with breast cancer. The women talked about having cancer as a transformative experience. Information about breast cancer from healthcare providers was …

Individual, Disease, And Work-Related Factors Associated With Work Patterns, Presenteeism And Sick Pay Policy Of The Colorectal Cancer Survivor After Treatment, Kristin A. Roper

Graduate Doctoral Dissertations

Participation of colorectal cancer survivors (CRC) in the workforce has been described by clinicians, survivors, and researchers as a way to improve mood, quality of life (QOL), and survival. Maintaining self-esteem and financial independence have also been attributed to continued employment of the CRC survivor. The purpose of this cross-sectional survey was to describe patterns of employment of the CRC survivor and to examine the individual, disease, and work-related factors that influence presenteeism and perceived adequacy of sick pay (ASP) policy. The Conceptual Model of Nursing and Health Policy and the Pathways to Work Life Recovery guided the design, selection …

Extracellular Pyruvate Kinase M2 Regulates Tumor Angiogenesis, Liangwei Li

Biology Dissertations

Pyruvate kinase M2 (PKM2) has been studied for decades on its role in cancer metabolism. Recently, PKM2 is highlighted again for its new function: promoting gene transcription by acting as a protein kinase. Moreover, the PKM2 levels in patient circulation have been used as a diagnostic marker for many types of cancers. However, it remains unclear whether PKM2 in blood circulation has any physiological or pathological function. In my dissertation, I demonstrate that PKM2 released from cancer cells facilitates tumor growth by promoting tumor angiogenesis. Our experiments show that PKM2 promotes endothelial cell proliferation, migration and survival. Only the dimeric …

The Role Of Lipocalin 2 In Early Stage Colon Cancer Metastasis To The Liver, Fides Elamparo

Senior Theses

Metastasis, frequently from the colon to the liver, is the major cause of death with colorectal cancer, reducing the five-year survival to less than 6%. Metastasis occurs due to productive collaborations between tumor cells and host-derived cells in the tumor microenvironment, where a pre-metastatic niche is created to prime for cancer cell invasion into the target organ. In a highly metastatic colorectal cancer cell line implanted into the cecum of Balb/c mice, microarray analysis showed lipocalin 2 (Lcn2) is one of the most highly expressed proteins in the liver of tumor-bearing mice prior to metastasis.

When RT-PCR was performed, greater …

Psychosocial Needs Of Children Coping With Parental Terminal Cancer In A Hospital Setting, Meredith Reed

Educational Specialist, 2009-2019

Cancer rates in the United States continue to be staggering. It is also heartbreaking to note that many of the adults confronting cancer are also parents of children. Parental terminal cancer poses a threat to the psychological well being of the entire family. Children are at a significantly higher risk for developing psychological disorders if their psychosocial needs are not met during this crucial time. Communication is vital in assisting children with their reactions to the illness and impending loss. Research has shown that communication between family members, especially with children, and also between medical professionals and families can often …

Identification Of Microrna Biomarkers In Her2-Positive Breast Cancer, Hossam Tashkandi

Theses and Dissertations

Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 30% of breast cancer patients with poor prognosis. In addition, microRNAs are small non-coding RNA that have been linked to many cancers. Here we investigate which miRNAs are differentially regulated by HER2 overexpression. Using quantitative reverse-transcription prolymerase chain reaction (QRT-PCR) and matching it with the clinical data acquired from Dvinge, we find five candidate miRNAs. When comparing the miRNAs’ effect on patient survival, only three miRNAs stand as good predictors of patient survival outcome. These miRNAs are miR-146a-5p, miR-181d, and miR-195-5p. When miR-146a-5p is up-regulated, which is the case …

Health Literacy And Cancer Prevention: A Qualitative Exploration Of The Health Communication Needs Of Hispanics Residing In Northeast Texas, Jessica R. Hyde

Health and Kinesiology Theses

Introduction: Limited health literacy can impede adherence to cancer screening guidelines. This problem transcends sociocultural boundaries; however, Hispanics are more likely to have limited health literacy than other racial/ethnic groups in the U.S. The purpose of this study is to explore health literacy at a conceptual level in Hispanic adults residing in Northeast Texas in order to better understand this population's communication needs related to cancer prevention. Methods: Focus group methodology and the Spanish-language version of the Newest Vital Sign (NVS-S) were used to gather data. Results: Of the 18 individuals who sat for the NVS-S, 6 were classified as …

The Effect Of Patient Education On Anxiety Levels In Patients Receiving Chemotherapy For The First Time, Sarah Garcia

Evidence-Based Practice Project Reports

Cancer affects approximately 1.5 million people every year throughout the United States.Comprehensive care that includes psychosocial aspects is important to help patients effectively adapt to their diagnosis and treatment plan. Improper prevention and management of anxiety can lead to poor psychosocial outcomes, dissatisfaction with care, and decreased adherence to treatment. Current evidence suggests that education is effective at helping reduce anxiety in patients receiving chemotherapy for the first time. The purpose of this evidenced based practice project was to determine if nurse-led patient education regarding chemotherapy side effects, side-effect management, and orientation to the infusion center was effective at decreasing …

Augmentation Of Ras-Induced Cell Transformation : A New Role For Mir-200a In Malignancy., Lindsey Erin Becker

Electronic Theses and Dissertations

Cancer is a multistep disease that begins with malignant cell transformation and frequently culminates in metastasis and death. MicroRNAs (miRNAs) are small regulatory 21-25-nt RNA molecules and are frequently deregulated in cancer. The majority of miRNAs are estimated to be co-expressed with neighboring miRNAs as clusters. Many miRNA clusters coordinately regulate multiple members of cellular signaling pathways or protein interaction networks. miR-200a is a member of the miR-200 family, which are known to be strong inhibitors of the epithelial to mesenchymal transition. As such, the tumor suppressive role of miR-200a in oncogenesis has been well studied; however, recent studies have …

Serving The Student-Survivor: Exploring The Transitional And Psychosocial Needs Of School-Aged Children With Cancer And Chronic Illness, Devon Malia Lanin

Dissertations, Masters Theses, Capstones, and Culminating Projects

The advances in medicine today have created an emerging population of student-survivors, school-aged children living with and/or recovering from serious health conditions (Bauman, 2010). Each school day in the United States, 46 young people, or the equivalent of two classrooms of students, learn they have cancer (Cure Search National Childhood Cancer Foundation, 2010). These statistics reflect the fact that cancer is one of the most chronic illnesses in childhood. Most serious childhood medical issues will have life-long ramifications. This qualitative research study is comprised of an in-depth review of the research literature and the responses and information gathered from two …

Gain-Of-Function Mouse Models To Investigate Biological Roles Of Prmt6, Alessandra Di Lorenzo

Dissertations & Theses (Open Access)

Gain-of-function Mouse Models to Investigate Biological Roles of PRMT6

Alessandra Di Lorenzo, Ph.D. Candidate

Mentor: Dr. Mark T. Bedford

Protein Arginine Methyltransferase 6 (PRMT6) is the histone tail writer that methylates the H3R2 (arginine 2 of histone H3) residue, which counteracts the activating H3K4me3 mark. PRMT6 has been shown to behave both as transcriptional co-repressor (i.e. trhrombospondin-1, p21, p53), and co-activator (nuclear receptors). The co-repressor function of PRMT6 is likely the result of H3K4me3 antagonism, while the mechanism by which PRMT6 exerts its co-activator function has yet to be elucidated. PRMT6 is over-expressed in several types of tumors including small …