Medicine and Health Sciences Commons^™

Isolation And Total Synthesis Of Sigma-2 Ligands From Marine Cyanobacteria, Andrea Hough

Electronic Theses and Dissertations

Cyanobacteria have been studied for over 50 years as a source of new antibiotics, antiviral, and anticancer drugs. The research described in this dissertation investigates marine cyanobacteria as a source of natural products with activity within the central nervous system and with cytotoxicity against breast cancer cells. Barbamide (1) is a known cyanobacterial metabolite that has been re-isolated from a variety of species and collection sites suggesting broad utility as a signaling molecule. Utilizing the psychoactive drug screening program, we screened barbamide for CNS activity and found that barbamide exhibited affinity for the kappa opioid receptor (KOR) and …

Perceived Social Support, Family Relationships, And Health-Related Quality Of Life Among Women With Breast Cancer In Jordan., Hedaya Rateb Hina

Electronic Theses and Dissertations

Introduction: Breast cancer is the most common cancer among Jordanian women. Perceived social support (PSS) and family relationships are strongly associated with positive psychosocial outcomes and health-related quality of life (HRQoL). This area was widely explored in Western countries, but little attention was devoted to investigate this area in Middle East region. Purpose: to investigate the interrelationships among PSS, family relationships, and HRQoL of women with breast cancer in Jordan using an exploratory cross-sectional design. Method: The contextual model of HRQoL designed by Ashing-Giwa (2005) provided the foundation for this study. A total of 140 women were …

Metabolic-Epigenetic Regulation Of Macrophage Polarization., Jordan T. Noe

Electronic Theses and Dissertations

Tumor-associated macrophages polarized to an M2 phenotype (M2-TAMs) promote neo-angiogenesis, tumor-stromal matrix remodeling, and immuno-evasion, which, collectively, contribute to immunotherapeutic resistance and reduced cancer patient survival. Highly glycolytic “Warburg” cancer cells produce lactate that independently drives naïve M0→immunosuppressive M2 (M0→M2) macrophage polarization, but the mechanisms have not been fully elucidated. The atypical cytokine macrophage migration inhibitory factor (MIF) is a fundamental underlying requirement for immunosuppressive M2 macrophage polarization. Still, it is unknown whether a molecular link exists between lactate-supported and MIF-dependent M2 macrophage polarization. Using a combination of gene expression assays, chromatin immunoprecipitation, and metabolomic analyses, we identified that M2 …

Qualitative Study Of Factors Contributing To Fertility Service Use Among Cancer Survivors Of Reproductive Age In The Us, Angela Rodgers Moore

Electronic Theses and Dissertations

Cancer remains the second leading cause of death in the United States; however, there has been a decline in incidence and mortality due to advances in screening and treatment. Currently 16.9 million survivors are thriving within the United States, and the population of cancer survivors has been projected to grow to 22.2 million by 2030. Although cancer survivors report an increased surge of vitality and vigor, they often face physical, mental, psychosocial, or financial challenges that threaten their quality of life. A late treatment effect of particular concern for cancer survivors of reproductive age that has both physical and psychosocial …

Association Of Perfluorinated Chemicals With Endocrino-Carcinogenetic, Obesogenic And Metabolic Health And With Markers Of Chronic Inflammation And Oxidative Stress, Ogbebor Enaholo Omoike

Electronic Theses and Dissertations

First, this study examined the association of perfluorinated chemicals with 1) cardio-metabolic health outcomes and 2) the association of phthalates with cardiometabolic health outcomes, and 3) cardio-metabolic health outcomes while assessing the possibility of additive interactions between perfluorinated chemicals (PFCs) and phthalates. Second, association with markers of chronic inflammation and oxidative stress were explored. Finally, this study examined the association of these chemicals with estrogenic cancers- Breast cancer, prostate cancer, uterine cancer and ovarian cancer.

Using data from the National Health and Nutrition Examination Survey (NHANES), logistic regression models were used to investigate the relationship between PFCs and the cardio-metabolic …

Analysis Of Tobacco Use Vital Sign Assessment, Latonya King

Electronic Theses and Dissertations

There is a massive problem of tobacco-related cancer outcomes in patients that are affected by race and ethnicity. Although this is a known disparity, there continues to be a gap in care for asking patients if they use tobacco and in advising and assisting them in making a quit attempt. Health information technology requirements and meaningful use regulations require the utilization of systematic electronic documentation. In order to improve and support tobacco use screening, systematic tobacco use assessment and documentation are essential. There is a widespread belief that adding screening for tobacco use to the vital sign assessment will lead …

Synthesis, Characterization, And Evaluation Of Metal Complexes With Cancer Selective Anti-Proliferative Effects And Hydrogen Evolution Catalytic Properties., Nicholas Vishnosky

Electronic Theses and Dissertations

Bis-thiosemicarbazones (BTSC) and their metal chelates have properties that are useful in several different scientific fields. These systems have already received attention in major fields of biology and engineering. Hydrogen evolution reaction (HER) catalysts need to be cheap and operate under minimal overpotentials with a long lifetime. The treatment of cancer requires, novel agents that have potent cytotoxic activity against cancer cells while displaying minimal side effects. In this dissertation the modular synthesis of these bis-thiosemicarbazone systems is utilized to regulate the redox chemistry for employment in the desired sector of chemistry. The ligand and metal chelates synthesized were characterized …

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …

A Cancer-Targeted Gold Nanoparticle-Based Mri Contrast Agent., Nagwa El-Baz

Electronic Theses and Dissertations

In oncology, imaging plays a major role in terms of early detection and treatment of most types of cancer. Magnetic resonance imaging (MRI) is mostly used for cancer diagnosis due to its excellent contrast resolution. However, MRI for cancer diagnosis is somewhat limited by its sensitivity. In this thesis, we assessed the ability of theranostic platform consisting of gold nanoparticles functionalized with a cancer targeting aptamer; AS1411 and gadolinium chelate (Dotarem thiol derivative; Gd (III)-DO3A) as a MRI contrast agent to target malignant tumors by enhancing the MRI contrast of the detected tumor. The proposed technology is a novel injectable …

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 …

The Interaction Of Homoserine Lactones And Paraoxonase 2 Modulates Cell Death Signaling And Cell Proliferation., Aaron Mackallan Neely

Electronic Theses and Dissertations

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Importantly, C12 induces apoptosis …

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …

Application Of The Misclassification Simulation Extrapolation (Mc-Simex) Procedure To Log-Logistic Accelerated Failure Time (Aft) Models In Survival Analysis, Varadan Sevilimedu

Electronic Theses and Dissertations

Survival analysis is the study of time to event outcomes. Accelerated Failure Time models (AFT) serve as a useful tool in survival analysis to study the time of occurrence of an event and its relation to the covariates of interest. The accuracy of estimation of parameters in a model depends upon the correct measurement of covariates. Considering that perfect measurement of covariates is highly unlikely, it is imperative that the performance of the existing bias-correction methods be analyzed in AFT models. However, certain areas of bias-correction in AFT models still remain unexplored. One of these unexplored areas, is a situation …

Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML) is a highly heterogeneous clonal disorder characterized by an accumulation of malignant immature myeloid progenitors in the bone marrow (BM) that hinder normal hematopoiesis. Patient AML exhibits a dramatic heterogeneity in terms of cytogenetics, disease morphology, and associated prognoses and/or chemotherapeutic sensitivity. Thus it becomes clearly evident that the investigation of novel therapeutics for AML will require model systems that are capable of recapitulating this stark heterogeneity in a patient specific manner. Furthermore, it is now understood that the surrounding bone marrow (BM) microenvironment and supporting cells play a critical role in leukemic progression as well …

The Discovery Of A Novel, Ras-Mediated Nore1a/Pmliv Tumor Suppressor Complex., Jessica Mezzanotte Sharpe

Electronic Theses and Dissertations

Ras is the most commonly activated oncogene in human cancer. Activated Ras drives cell growth and proliferation by activating multiple mitogenic signaling pathways. However, Ras also has the paradoxical ability to promote anti-growth, pro-apoptotic, and pro-senescent signaling. The signaling pathways of many of these biological effectors remain poorly defined. One group of proteins capable of promoting Ras-induced apoptosis and cell cycle arrest is the RASSF family of tumor suppressors. Novel Ras Effector 1A, or NORE1A, was the first member of this family discovered and is a bona fide tumor suppressor that is lost or inactivated in a number of different …

Life Balance In Adult Healthy Siblings Of Individuals With Childhood Cancer., Yolanda Williams

Electronic Theses and Dissertations

Siblings of children who were diagnosed with cancer in childhood experience significant stress and psychological difficulties as a result of the cancer. Furthermore, the needs of siblings have often been overlooked in the cancer literature, prompting the need for more studies. The purpose of this dissertation is to examine the life balance and social support outcomes of adults who grew up in the household with a sibling that was diagnosed with cancer. The study sample consisted of 120 adult healthy siblings who grew up in a household with a sibling that was diagnosed with cancer prior to age 19. Participants …

Immunomodulation Of Myeloid-Derived Suppressor Cells By Particulate B-Glucan In Cancer., Sabrin Husein Albeituni

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we investigated the effect of dectin-1 stimulation by yeast-derived particulate β-glucan in MDSC function and differentiation in cancer. In vivo treatment of mice bearing lewis lung carcinoma and mammary cell carcinoma with particulate β-glucan decreased tumor weight and splenomegaly, and reduced the accumulation of polymorphonuclear-MDSC (PMN-MDSC) but not monocytic-MDSC (M-MDSC) in the spleen and tumor. In addition, particulate β-glucan differentially modulated the function of different MDSC subsets; it enhanced PMN-MDSC respiratory burst and apoptosis, and induced the differentiation of M-MDSC into …

Family Care Giver Knowledge, Patient Illness Characteristics, And Unplanned Hospital Admissions In Older Adults With Cancer, Patricia Geddie

Electronic Theses and Dissertations

Unplanned hospital admissions (UHA) in older adult populations are a recurring problem in older adults with cancer. Older adults comprise approximately 60% of cancer diagnoses and receive the majority of cancer treatment. However, little is known about why older adults under treatment for cancer experience a high number of unplanned hospital admissions. A review of the literature provided few study findings and a gap in the current knowledge was identified regarding the factors associated with unplanned hospital admissions in older adults under treatment for cancer. A conceptual framework based on the literature and this researcher's clinical experienced guided this study. …

Examining Stage At Diagnosis And Survival In Three Cancers With Definitive Screening Guidelines For Average-Risk Adults: The Role Of Marital Status, David J. Blackley

Electronic Theses and Dissertations

Each year there are more than 350 000 new cases and nearly 100 000 deaths attributed to colorectal, female breast, and cervical cancer in the United States. Screening tests can reduce morbidity and mortality associated with these cancers. Patient marital status has been associated with health outcomes, but no study has focused on the relationship of marriage with disease stage and survival for the 3 cancers with established screening guidance. It is critical to identify special populations that may be at risk for poor cancer outcomes.

The objective of this study was to examine the relationship of marital status with …

Exploring The Unique Characteristics Of Cancer In Adolescents And Young Adults In Tennessee, Megan Quinn

Electronic Theses and Dissertations

Adolescents and Young Adults (AYAs) ages 15-39 years with cancer have received little attention in the medical and health fields, resulting in a lack of progress for this age group. Little is known about the unique biologic, epidemiologic, and psychosocial issues that play an integral role in the AYA cancer journey. The purposes of this study were to use the Tennessee Cancer Registry for all new cancer cases from 2004-2008 to determine 1) the main types of cancer that affect AYAs in TN, 2) the predictors of late-stage diagnosis of melanoma, and 3) the factors that predict a total thyroidectomy …

Impact Of Cancer-Specific Advance Care Planning On Anxiety, Decisional Conflict, And Surrogate Understanding Of Patient Treatment Preferences, Lynn Waser

Electronic Theses and Dissertations

Patients with life-limiting cancer and their families face unique challenges that interfere with their ability to make decisions or adequately express their health care preferences about end of life (EOL) treatment. As a result, patients at EOL often receive aggressive unwanted treatment that nationally costs billions of dollars and results in surrogate distress about not honoring patient wishes. Respecting Choices® DS-ACP is a disease-specific Advance Care Planning (ACP) intervention that is designed to overcome barriers associated with ACP and potentially decrease the incidence of unwanted, overly aggressive treatments at EOL. The intervention is delivered to patient-surrogate dyads by a trained …

Stem Cell Biology And Strategies For Therapeutic Development In Degenerative Diseases And Cancer, Angel A. Alvarez

Electronic Theses and Dissertations

Stem cell biology is an exciting field that will lead to significant advancements in science and medicine. We hypothesize that inducing the expression of stem cell genes, using the embryonic stem cell gene nanog, will reprogram cells and dedifferentiate human mesenchymal stem cells into pluripotent stem cells capable of neural differentiation. The aims of initial studies are as follows: Aim 1: Demonstrate that forced expression of the embryonic stem cell gene nanog induces changes in human mesenchymal stem cells to an embryonic stem cell-like phenotype. Aim 2: Demonstrate that induced expression of nanog up-regulates the expression of multiple embryonic stem …

Synthesis Of A Water Soluble Resveratrol Derivative As A Potential Anti-Cancer Drug., Augustine Essel

Electronic Theses and Dissertations

Research on development of water soluble anti-cancer drugs is one of the great challenges of modern medicinal chemistry. Resveratrol (Res) is one of the many phytoalexins producing stilbenoids present in several medicinal plants, grape skin, peanuts, and red wine. It has been found to exhibit anti-cancer, anti-inflammatory, and anti-oxidant properties. Water solubility and bioavailability are some of the setbacks of this interesting compound. In view of this, effort has been made to synthesize amino acid derivative of resveratrol to improve its bioavailability and solubility in water. Methyl 4-{-[(1E)-2-(3, 5-dihydroxyphenyl)-ethenyl] - phenoxy} butyrate (7), a novel ester intermediate, has been synthesized …

Synthesis Of Marine Chemicals And Derivatives As Potential Anti-Cancer Drugs., Laude Bannerman-Akwei

Electronic Theses and Dissertations

Two natural marine compounds, 3-bromo-4,5-dihydroxybenzaldehyde 2 and 2,3-dibromo-4,5-dihydroxybenzaldehyde 5 together with two novel derivatives, 3-bromo-5-(tert-butyl-dimethyl-silanyloxy)-4-hydroxybenzaldehyde 3 and 1-bromo-2,3-dimethoxy-5-nitrooxy-methylbenzene 9, were synthesized. Compounds 2, 3, and 5 were evaluated for their biological activity towards the inhibition of prostate cancer cell growth using staurosporine a a positive control. All three compounds have shown significant inhibition of prostate cancer cell growth. Compound 9 is yet to be evaluated.